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Sulphonylurea monotherapy for patients with type 2 diabetes mellitus

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Referencias

References to studies included in this review

Ir a:

Abbatecola 2006 {published data only}

Abbatecola AM, Rizzo MR, Barbieri M, Grella R, Arciello A, Laieta MT, et al. Postprandial plasma glucose excursions and cognitive functioning in aged type 2 diabetics. Neurology 2006;67(2):235‐40. [PUBMED: 16864814]

ADOPT 2006 {published and unpublished data}

GlaxoSmithKline. Diabetes study with rosiglitazone monotherapy versus metformin or glyburide/glibenclamide. ClinicalTrials.gov2006. [NCT00279045]
Home PD, Kahn SE, Jones NP, Noronha D, Beck‐Nielsen H, Viberti G, et al. Experience of malignancies with oral glucose‐lowering drugs in the randomised controlled ADOPT (A Diabetes Outcome Progression Trial) and RECORD (Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycaemia in Diabetes) clinical trials. Diabetologia 2010;53(9):1838‐45.
Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. [Erratum appears in N Engl J Med. 2007 Mar 29;356(13):1387‐8]. New England Journal of Medicine 2006;355(23):2427‐43.
Krall RL. Cardiovascular safety of rosiglitazone. Lancet 2007;369(9578):1995‐6. [DOI: 10.1016/S0140‐6736(07)60824‐1]
Lachin JM, Viberti G, Zinman B, Haffner SM, Aftring RP, Paul G, et al. Renal function in type 2 diabetes with rosiglitazone, metformin, and glyburide monotherapy. Clinical Journal of the American Society of Nephrology 2011;6(5):1032‐40.
Viberti G, Kahn SE, Greene DA, Herman WH, Zinman B, Holman RR, et al. A diabetes outcome progression trial (ADOPT): an international multicenter study of the comparative efficacy of rosiglitazone, glyburide, and metformin in recently diagnosed type 2 diabetes. Diabetes Care 2002;25(10):1737‐43.
Viberti G, Lachin J, Holman R, Zinman B, Haffner S, Kravitz B, et al. A Diabetes Outcome Progression Trial (ADOPT): baseline characteristics of Type 2 diabetic patients in North America and Europe. Diabetic Medicine 2006;23(12):1289‐94.

AGEE/DCD/046/UK {unpublished data only}

Center for Drug Evaluation and Research. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/020741_S009_PRANDIN_TABS_AP.pdf.
Novo Nordisk. AGEE/DCD/046/UK. Synopsis of the trial.

AGEE/DCD/047/B/F/I {unpublished data only}

Center for Drug Evaluation and Research. http://www.accessdata.fda.gov/drugsatfda_docs/nda/2000/020741_S009_PRANDIN_TABS_AP.pdf.
Novo Nordisk. AGEE/DCD/047/B/F/I. Synopsis of the trial.

Alvarsson 2010 {published data only}

Alvarsson M, Berntorp K, Fernqvist‐Forbes E, Lager I, Steen L, Orn T, et al. Effects of insulin versus sulphonylurea on beta‐cell secretion in recently diagnosed type 2 diabetes patients: a 6‐year follow‐up study. Review of Diabetic Studies 2010;7(3):231‐8.
Alvarsson M, Sundkvist G, Lager I, Berntorp K, Fernqvist‐Forbes E, Steen L, et al. Effects of insulin vs. glibenclamide in recently diagnosed patients with type 2 diabetes: a 4‐year follow‐up. Diabetes, Obesity & Metabolism 2008;10(5):421‐9.
Alvarsson M, Sundkvist G, Lager I, Henricsson M, Berntorp K, Fernqvist‐Forbes E, et al. Beneficial effects of insulin versus sulphonylurea on insulin secretion and metabolic control in recently diagnosed type 2 diabetic patients. Diabetes Care 2003;26(8):2231‐7.

APPROACH 2010 {published and unpublished data}

Rosiglitazone versus a sulfonylurea on progression of atherosclerosis in patients with heart disease and type 2 diabetes. http://clinicaltrials.gov/ct2/show/NCT00116831?term=nct00116831&rank=12005. [NCT00116831]
Gerstein HC, Ratner RE, Cannon CP, Serruys PW, García‐García HM, van Es GA, et al. Effect of rosiglitazone on progression of coronary atherosclerosis in patients with type 2 diabetes mellitus and coronary artery disease: the assessment on the prevention of progression by rosiglitazone on atherosclerosis in diabetes patients with cardiovascular history trial. Circulation 2010;121(10):1176‐87.
Ratner RE, Christopher PC, Gerstein HC, Nesto RW, Serruys PW, van Es GA, et al. Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in diabetes patients with Cardiovascular History (APPROACH): study design and baseline characteristics. American Heart Journal 2008;156(6):1074‐9.

Birkeland 1994 {published and unpublished data}

Birkeland KI, Furuseth K, Melander A, Mowinckel P, Vaaler S. Long‐term randomized placebo‐controlled double‐blind therapeutic comparison of glipizide and glyburide. Glycemic control and insulin secretion during 15 months. Diabetes Care 1994;17(1):45‐9.

Birkeland 2002 {published and unpublished data}

Birkeland KI, Hanssen KF, Urdal P, Berg K, Vaaler S. A long‐term, randomized, comparative study of insulin versus sulfonylurea therapy in type 2 diabetes. Journal of Internal Medicine 1994;236(3):305‐13.
Birkeland KI, Kilhovd B, Thorsby P, Torjesen PA, Ganss R, Vaaler S, et al. Heterogeneity of non‐insulin‐dependent diabetes expressed as variability in insulin sensitivity, beta‐cell function and cardiovascular risk profile. Diabetic Medicine 2002;20:37‐45.
Birkeland KI, Rishaug U, Hanssen KF, Vaaler S. NIDDM: a rapid progressive disease. Results from a long‐term, randomised, comparative study of insulin or sulphonylurea treatment. Diabetologia 1996;39(12):1629‐33.

Campbell 1994 {published data only}

Campbell IW, Menzis DG, Chalmers J, McBain AM, Brown IRF. One year comparative trial of metformin and glipizide in type 2 diabetes mellitus. Diabète & Métabolisme 1994;20(4):394‐400.

Charbonnel 2005 {published data only}

Charbonnel B, Roden M, Urquhart R, Mariz S, Johns D, Mihm M, et al. Pioglitazone elicits long‐term improvements in insulin sensitivity in patients with type 2 diabetes: comparisons with gliclazide‐based regimens. Diabetologia 2005;48(3):553‐60. [PUBMED: 15739120]
Charbonnel BH, Matthews DR, Schernthaner G, Hanefeld M, Brunetti P, QUARTET Study. A long‐term comparison of pioglitazone and gliclazide in patients with type 2 diabetes mellitus: a randomized, double‐blind, parallel‐group comparison trial. Diabetic Medicine 2005;22(4):399‐405. [PUBMED: 15787663]

Collier 1989 {published data only}

Collier A, Watson HH, Patrick AW, Ludlam CA, Clarke BF. Effect of glycaemic control, metformin and gliclazide on platelet density and aggregability in recently diagnosed type 2 (non‐insulin‐dependent) diabetic patients. Diabète & Métabolisme 1989;15(6):420‐5.

Coniff 1995 {published data only}

Coniff RF, Shapiro JA, Seaton TB, Bray GAB. Multicenter, placebo‐controlled trial comparing acarbose (BAY g 5421) with placebo, tolbutamide, and tolbutamide‐plus‐acarbose in non‐insulin‐dependent diabetes mellitus. American Journal of Medicine 1995;98(5):443‐51. [EMBASE: 1995143472]

Dalzell 1986 {published data only}

Dalzell GW, Hadden DR, Atkinson AB, Kennedy L, Weaver JA. A randomized trial of tolbutamide and metformin for persistent severe hypoglycaemia in non insulin dependent diabetes mellitus (NIDDM). Irish Endocrine Society 1986;155(9):341‐42.

DeFronzo 1995 {published data only}

DeFronzo RA, Goodman AM, and the Multicenter Metformin Study Group. Efficacy of metformin in patients with non‐insulin‐dependent diabetes mellitus. New England Journal of Medicine1995; Vol. 333, issue 9:541‐9.

Deng 2003 {published data only}

Deng QW. Clinical observation on Xiayaosan modified for treatment of type 2 diabetes mellitus. Hubei Journal of Traditional Chinese Medicine 2003;25(12):31‐2.

Derosa 2003 {published data only}

Derosa G, Mugellini A, Ciccarelli L, Crescenzi G, Fogari R. Comparison between repaglinide and glimepiride in patients with type 2 diabetes mellitus: a one‐year, randomized, double‐blind assessment of metabolic parameters and cardiovascular risk factor. Clinical Therapeutics 2003;25(2):472‐84.

Derosa 2004 {published data only}

Derosa G, Franzetti I, Gadaleta G, Ciccarelli L, Fogari R. Metabolic variations with oral antidiabetic drugs in patients with Type 2 diabetes: comparison between glimepiride and metformin. Diabetes, Nutrition & Metabolism 2004;17(3):143‐50. [PUBMED: 15334791]

Diehl 1985 {published and unpublished data}

Diehl AK, Sugarek NJ, Bauer RL. Medication compliance in non‐insulin‐dependent diabetes: a randomized comparison of chlorpropamide and insulin. Diabetes Care 1985;8(3):219‐23. [PUBMED: 3891264]

Ebeling 2001 {published data only}

Ebeling P, Teppo A, Koistinen HA, Koivisto VA. Concentration of the complement activation product, acylation‐stimulating protein, is related to C‐reactive protein in patients with type 2 diabetes. Metabolism 2001;50(3):283‐7. [PUBMED: 11230779]

Esposito 2004 {published data only}

Esposito K, Giugliano D, Nappo F, Marfella R for Campanian Postprandial Hyperglycemia Study Group. Regression of carotid atherosclerosis by control of postprandial hyperglycemia in type 2 diabetes mellitus. Circulation 2004;110(2):214‐9. [PUBMED: 15197140]

Feinböck 2003 {published data only}

Feinböck C, Luger A, Klingler A, Egger T, Bielesz GK, Winkler F, et al. Prospective multicentre trial comparing the efficacy of, and compliance with, glimepiride or acarbose treatment in patients with type 2 diabetes not controlled with diet alone. Diabetes, Nutrition & Metabolism 2003;16(4):214‐21. [PUBMED: 14768770]

Fineberg 1980 {published data only}

Fineberg SE, Schneider SH. Glipizide versus tolbutamide, an open trial. Effects on insulin secretory patterns and glucose concentrations. Diabetologia 1980;18(1):49‐54.

Foley 2009 {published data only}

Foley JE, Sreenan S. Efficacy and safety comparison between the DPP‐4 inhibitor vildagliptin and the sulfonylurea gliclazide after two years of monotherapy in drug‐naive patients with type 2 diabetes.[Erratum appears in Horm Metab Res. 2009 Dec;41(12):909]. Hormone & Metabolic Research 2009;41(12):905‐9.
www.clinicaltrials.gov. Efficacy and safety of vildagliptin compared to gliclazide in drug naive patients with type 2 diabetes. http://clinicaltrials.gov/ct2/show/NCT00102388?term=nct00102388&rank=1. [NCT00102388]

Forst 2003 {published data only}

Forst T, Eriksson JW, Strotmann HJ, Bai S, Brunelle R, Gulliya KS, et al. Metabolic effects of mealtime insulin lispro in comparison to glibenclamide in early type 2 diabetes. Experimental and Clinical Endocrinology & Diabetes 2003;111(2):97‐103.

Forst 2005 {published data only}

Forst T, Hohberg C, Fuellert SD, Lübben G, Konrad T, Löbig M, et al. Pharmacological PPARgamma stimulation in contrast to beta cell stimulation results in an improvement in adiponectin and proinsulin intact levels and reduces intima media thickness in patients with type 2 diabetes. Hormone and Metabolic Research 2005;37(8):521‐7.
Forst T, Lübben G, Hohberg C, Kann P, Sachara C, Gottschall V, et al. Influence of glucose control and improvement of insulin resistance on microvascular blood flow and endothelial function in patients with diabetes mellitus type 2. Microcirculation2005; Vol. 12, issue 7:543‐50.

Hanefeld 2011 {published data only}

Charbonnel B, Lonnqvist F, Jones NP. Rosiglitazone is superior to glyburide in reducing fasting plasma glucose after one year of treatment in type 2 diabetic patients. Diabetes. 1999; Vol. 48 (Suppl 1).
GlaxoSmithKline. A multicentre, double‐blind, parallel group comparative study to evaluate the efficacy, safety and tolerability of rosiglitazone vs. glibenclamide therapy, when administered to patients with type 2 diabetes mellitus. GlaxoSmithKline Clinical Study Register (http://www.gsk‐clinicalstudyregister.com/)2011. [49653/020]
Hanefeld M, Patwardhan R, Jones NP. A one‐year study comparing the efficacy and safety of rosiglitazone and glibenclamide in the treatment of type 2 diabetes. Nutrition, Metabolism, and Cardiovascular Diseases 2007;17(1):13‐23. [PUBMED: 17174222]

Harrower 1985 {published and unpublished data}

Harrower AD. Comparison of diabetic control in type 2 (non‐insulin dependent) diabetic patients treated with different sulphonylureas. Current Medical Research and Opinion 1985;9(10):676‐80.

Hermann 1991 {published and unpublished data}

Hermann LS, Karlsson JE, Sjöstrand A. Prospective comparative study in NIDDM patients of metformin and glibenclamide with special reference to lipid profiles. European Journal of Clinical Pharmacology 1991;41(3):263‐5.

Hermann 1991a {published and unpublished data}

Hermann LS, Bitzén PO, Kjellström T, Lindgärde F, Scherstén B. Comparative efficacy of metformin and glibenclamide in patients with non‐insulin‐dependent diabetes mellitus. Diabète & Métabolisme 1991;17:201‐8.
Hermann LS, Kjellström T, Nilsson‐Ehle P. Effects of metformin and glibenclamide alone and in combination on serum lipids and lipoproteins in patients with non‐insulin‐dependent diabetes mellitus. Diabète & Métabolisme 1991;17:174‐9.
Hermann LS, Scherstén B, Bitzén PO, Kjellström T, Lindgärde F, Melander A. Therapeutic comparison of metformin and sulfonylurea, alone and in various combinations. A double‐blind controlled study. Diabetes Care 1994;17(10):1100‐9.
Hermann LS, Scherstén B, Melander A. Antihyperglycaemic efficacy, response prediction and dose‐response relations of treatment with metformin and sulphonylurea, alone and in primary combination. Diabetic Medicine 1994;11(10):953‐60.

Hoffmann 1990 {published data only}

Hoffmann J. Acarbose and glibenclamide in type‐II diabetes. A comparative study on efficacy and side effects (therapeutical news) [Acarbose ung Glibenclamid bei Type‐II Diabetes. Eine Vergleichsstudie zu Wirksamkeit und Nebenwirkungen]. Münchener Medizinische Wochenschrift 1990;132(31‐2):487‐90.
Hoffmann JK. Adjustment of metabolism and eating behaviour of type II diabetics. Results of a six‐months treatment with glibenclamide, respectively with acarbose. Zeitschrift für Allgemeinmedizin 1992;68(29):970‐7.

Hoffmann 1994 {published data only}

Hoffmann J, Spengler M. Efficacy of 24‐week monotherapy with acarbose, glibenclamide, or placebo in NIDDM patients. The Essen Study. Diabetes Care 1994;17(6):561‐6.

Hollander 1992 {published data only}

Hollander P, Bunkerslawson T, Bergenstal R, Mazze R. A randomized clinical trial of glyburide versus insulin using staged diabetes management to achieve euglycemia in NIDDM. Diabetologia. 1992; Vol. 35:A198.

Jain 2006 {published data only}

Jain R, Osei K, Kupfer S, Perez AT, Zhang J. Long‐term safety of pioglitazone versus glyburide in patients with recently diagnosed type 2 diabetes mellitus. Pharmacotherapy 2006;26(10):1388‐95.

Jibran 2006 {published data only}

Jibran R, Suliman MI, Qureshi F, Ahmed M. Safety and efficacy of repaglinide compared with glibenclamide in the management of type 2 diabetic Pakistani patients. Pakistan Journal of Medical Sciences 2006;22(4):385‐90. [EMBASE: 2006608997]

Johnston 1997 {published data only}

Johnston PS, Lebovitz HE, Coniff RF, Simonson DC, Raskin P, Munera CL. Advantages of alpha‐glucosidase inhibition as monotherapy in elderly type 2 diabetic patients. Journal of Clinical Endocrinology and Metabolism 1997;83(5):1515‐22.

Kaku 2011 {published and unpublished data}

Kaku K, Rasmussen MF, Nishida T, Seino Y. Fifty‐two‐week, randomized, multicenter trial to compare the safety and efficacy of the novel glucagon‐like peptide‐1 analog liraglutide vs glibenclamide in patients with type 2 diabetes. Journal of Diabetes Investigation 2011;2(6):441‐7. [DOI: 10.1111/j.2040‐1124.2011.00128.x]
Seino Y, Rasmussen MF, Katayama Y, Kaku K. Liraglutide is statistically superior to glibenclamide at controlling glycemia and weight, with low hypoglycemic risk, and improves beta‐cell function in Japanese Subjects with T2D. Diabetes. 2009; Vol. Conference: 69th Annual Meeting of the American Diabetes Association New Orleans, LA United States. Conference Start: 20090605 Conference End: 20090609.
Seino Y, Rasmussen MF, Nishida T, Kaku K. Efficacy and safety of the once‐daily human GLP‐1 analogue, liraglutide, vs glibenclamide monotherapy in Japanese patients with type 2 diabetes. Current Medical Research and Opinion 2010;26(5):1013‐22.
Zdravkovic M. Effect of liraglutide on blood glucose control in subjects with type 2 diabetes. www.clinicaltrials.gov2006. [NCT00393718]

Kamel 1997 {published data only}

Kamel AN, Cetinarslan B, Uysal AR, Baskal N, Corapcioglu D, Tonyukuk V. Efficacy of monotherapy with acarbose, glibenclamide, gliclazide, metformin or placebo in NIDDM patients. Diabetologia 1997;40(Suppl 1):1255.

Kanda 1998 {published data only}

Kanda T. Effects of oral antidiabetic agent on carbohydrate and lipid metabolism in mildly obese patients with diabetes mellitus: a randomized comparative study of acarbose and sulfonylurea [Keido Himan Tonyobyo Kanja no To, Shishitsu Taisha ni Oyobosu Keiko Tonyobyoyaku no Eikyo: Acarbose to SU Zai ni Yoru Randamuka Hikaku Shiken]. Rinsho to Kenkyu (The Japanese Journal of Clinical and Experimental Medicine) 1998;75(12):2757‐63.

Kovacevic 1997 {published data only}

Kovacevic I, Profozic V, Skrabalo Z, Cabrijan T, Zjacic‐Rotkvic V, Goldoni V, et al. Multicentric clinical trial to assess efficacy and tolerability of acarbose (BAY G 5421) in comparison to glibenclamide and placebo. Diabetologia Croatica 1997;26(2):83‐9. [EMBASE: 1997304622]

Lawrence 2004 {published data only}

Lawrence JM, Reid J, Taylor GJ, Stirling C, Reckless JP. Favorable effects of pioglitazone and metformin compared with gliclazide on lipoprotein subfractions in overweight patients with early type 2 diabetes. Diabetes Care 2004;27(1):41‐6.

LEAD‐3 2006 {published data only}

Bode BW, Testa MA, Magwire M, Hale PM, Hammer M, Blonde L, et al. Patient‐reported outcomes following treatment with the human GLP‐1 analogue liraglutide or glimepiride in monotherapy: results from a randomized controlled trial in patients with type 2 diabetes. Diabetes, Obesity and Metabolism2010; Vol. 12, issue 7:604‐12.
Garber A, Henry R, Ratner R, Garcia‐Hernandez PA, Rodriguez‐Pattzi H, Olvera‐Alvarez I, et al. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD‐3 Mono): a randomised, 52‐week, phase III, double‐blind, parallel‐treatment trial. Lancet 2009;373(9662):473‐81.
Garber A, Henry R, Ratner R, Hale P, Chang CT, Bode B. Liraglutide, a human GLP‐1 analogue, offers sustained and greater reduction in HbA1c, fasting plasma glucose and weight compared with glimepiride over 2 years, with lower hypoglycaemic risk, in patients with Type 2 diabetes: LEAD‐3 extension study. Diabetic Medicine. 2009; Vol. Conference: Diabetes UK Annual Professional Conference Liverpool United Kingdom, issue var.pagings.
Garber A, Henry RR, Ratner R, Hale P, Chang CT, Bode B. Liraglutide, a once‐daily human glucagon‐like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes. Diabetes, Obesity and Metabolism 2011;13(4):348‐56.
Garber AJ, Henry R, Ratner R, Hale P, Chang CT, Bode B. Liraglutide, a human GLP‐1 analogue, maintains greater reductions in HbA1c, FPG and weight than glimepiride over 2 years in patients with type 2 diabetes: LEAD‐3 extension study. Diabetologia2009; Vol. Conference: 45th EASD Annual Meeting of the European Association for the Study of Diabetes Vienna Austria.
Hale P. To evaluate the effect of liraglutide versus glimepiride (Amaryl©) on haemoglobin A1c (LEAD‐3). ClinicalTrials.gov2006. [NCT00294723]

Madsbad 2001 {published and unpublished data}

Madsbad S, Kilhovd B, Lagert I, Mustajoki P, Dejgaard A. Comparison between repaglinide and glipizide in type 2 diabetes mellitus: a 1‐year multicentre study. Diabetic Medicine 2001;18(5):395‐401.

Marbury 1999 {published and unpublished data}

Marbury T, Huang WC, Strange P, Lebovitz H. Repaglinide versus glyburide: a one‐year comparison trial. Diabetes Research and Clinical Practice 1999;43(3):155‐66.

Memisogullari 2009 {published data only}

Memisogullari R, Akcay F, Coskun A, Korkmaz U. Comparison of gliclazide treatment with diet therapy on acute phase protein levels in patients with type 2 diabetes. Turkish Journal of Medical Sciences 2009;39(1):73‐6.

Nakamura 2004 {published data only}

Nakamura T, Matsuda T, Kawagoe Y, Ogawa H, Takahashi Y, Sekizuka K, et al. Effect of pioglitazone on carotid intima‐media thickness and arterial stiffness in type 2 diabetic nephropathy patients. Metabolism: Clinical and Experimental 2004;53(10):1382‐6.

Nakamura 2006 {published and unpublished data}

Nakamura T, Sugaya T, Kawagoe Y, Ueda Y, Koide H. Effect of pioglitazone on urinary liver‐type fatty acid‐binding protein concentrations in diabetes patients with microalbuminuria. Diabetes/Metabolism Research and Reviews 2006;22(5):385‐9.

Nathan 1988 {published data only}

Nathan DM, Roussell A, Godine JE. Glyburide or insulin for metabolic control in non‐insulin‐dependent diabetes mellitus. A randomized, double‐blind study. Annals of Internal Medicine 1988;108(3):334‐40.

Pagano 1995 {published data only}

Marena S, Pagani A. Miglitol vs glibenclamide in non‐insulin dependent diabetes mellitus [abstract]. European Journal of Clinical Investigation1993; Vol. 23 Suppl 1:A43.
Marena S, Pagani A, Montegrosso G, Boella G, Pagano A, De Michieli F, et al. Comparison of miglitol and glibenclamide in non insulin‐dependent diabetic patients. Giornale Italiano di Diabetologia 1993;13(4):383‐8.
Pagano G, Marena S, Corgiat‐Mansin L, Cravero F, Giorda C, Bozza M, et al. Comparison of miglitol and glibenclamide in diet‐treated type 2 diabetic patients. Diabète & Métabolisme 1995;21(3):162‐7. [PUBMED: 7556806]

Perriello 2007 {published data only}

Perriello G, Pampanelli S, Brunetti P, Di Pietro C, Mariz S, Italian Pioglitazone Study. Long‐term effects of pioglitazone versus gliclazide on hepatic and humoral coagulation factors in patients with type 2 diabetes. Diabetes & Vascular Disease Research 2007;4(3):226‐30.
Perriello G, Pampanelli S, Di Pietro C, Brunetti P, Italian Pioglitazone Study. Comparison of glycaemic control over 1 year with pioglitazone or gliclazide in patients with type 2 diabetes. Diabetic Medicine 2006;23(3):246‐52.

Rosenthal 2002 {published data only}

Mauersberger H, Rosenthal JH. [Wirkung von endogenem Insulin sowie Acarbose oder Glibenclamide in der Therapie der Hypertonie bei Typ‐2 Diabetikern]. CF‐Journal 2001;1:26‐8.
Rosenthal J, Mauersberger H. Hypertension in type 2 diabetic patients‐ effects of endogenous insulin and antidiabetic therapies. American Journal of Hypertension 2000;13(4 Suppl 1):S81. [MEDLINE: 495]
Rosenthal JH, Mauersberger H. Effects on blood pressure of the alpha‐glucosidase inhibitor acarbose compared with the insulin enhancer glibenclamide in patients with hypertension and type 2 diabetes mellitus. Clinical Drug Investigation 2002;22(10):701. [MEDLINE: 492]

Salman 2001 {published data only}

Salman S, Salman F, Satman I, Yilmaz Y, Özer E, Sengül A, et al. Comparison of acarbose and gliclazide as first‐line agents in patients with type 2 diabetes. Current Medical Research and Opinion2001; Vol. 16, issue 4:296‐306.

Segal 1997 {published data only}

Segal P, Feig PU, Schernthaner G, Ratzmann KP, Rybka J, Petzinna D, et al. The efficacy and safety of miglitol therapy compared with glibenclamide in patients with NIDDM inadequately controlled by diet alone. Diabetes Care 1997;20(5):687‐91.

Shihara 2011 {published data only}

Shihara N. A comparative study of insulin secretagogue (SU agent) and insulin sensitizers (TZD). http://apps.who.int/trialsearch/trial.aspx?trialid=JPRN‐UMIN0000045822010. [JPRN‐UMIN000004582]
Shihara N, Kitaoka M, Inagaki N, Kadowaki T, Koumoto S, Satoh J, et al. Randomized controlled trial of single‐agent glimepiride and pioglitazone in Japanese patients with type 2 diabetes: a comparative study. Journal of Diabetes Investigation 2011;2(5):391‐8. [DOI: 10.1111/j.2040‐1124.2011.00115.x]

Spengler 1992 {published data only}

Fölsch UR, Spengler M, Boehme K, Sommerauer B. Efficacy of glucosidase inhibitors compared to sulphonylureas in the treatment and metabolic control of diet treated type 2 diabetic subjects: two long‐term comparative studies. Diabetes, Nutrition and Metabolism 1990;3(Suppl 1):63‐8.
Spengler M, Hänsel G, Boehme K. 6 months monotherapy of NIDDM with acarbose or glibenclamide. In: Lefébrevre PJ, Standl E editor(s). New Aspects in Diabetes. Treatment strategies with Alpha‐Glucosidase Inhibitors. Third International Symposium on Acarbose:. Berlin‐New York: Walter de Gryter, 1992:243‐6.
Spengler M, Hänsel G, Boehme K. Efficacy of 6 months monotherapy with glucosidase inhibitor Acarbose versus sulphonylurea glibenclamide on metabolic control of dietary treated type II diabetics (NIDDM). Hormone and Metabolic Research.Supplement Series 1992;26(Suppl 26):50‐1. [PUBMED: 1490692]
Spengler M, Hänsel M, Boehme K. Acarbose and glibenclamide in type II diabetes [Acarbose und Glibenclamid bei Typ‐II‐Diabetes]. Zeitschrift für Allgemeinmedizin 1990;65(22):606‐10.
Spengler N, Hänsel G, Boehme K. Efficacy of 6 months monotherapy with glucosidase inhibitor acarbose versus sulphonylurea glibenclamid on metabolic control of dietary treated type II diabetics. European Journal of Clinical Investigation 1989;19 (2 Pt II):A71.

Sung 1999 {published data only}

Sung BH, Izzo JL, Dandona P, Wilson MF. Vasodilatory effects of troglitazone improve blood pressure at rest and during mental stress in type 2 diabetes mellitus. Hypertension 1999;34(1):83‐8.

Sutton 2002 {published data only}

Bakris GL, Ruilope LM, McMorn SO, Weston WM, Heise MA, Freed MI, et al. Rosiglitazone reduces urinary albumin excretion. Journal of Human Hypertension 2003;17(1):7‐12.
St John Sutton M, Rendell M, Dandona P, Dole JF, Murphy K, Patwardhan R, et al. A comparison of the effects of rosiglitazone and glyburide on cardiovascular function and glycemic control in patients with type 2 diabetes. Diabetes Care 2002;25(11):2058‐64.

Tan 2004 {published data only}

Tan M, Johns D, González Gálvez G, Antúnez O, Fabián G, Flores‐Lozano F, et al. Effects of pioglitazone and glimepiride on glycemic control and insulin sensitivity in Mexican patients with type 2 diabetes mellitus: a multicenter, randomized, double‐blind, parallel‐group trial. Clinical Therapeutics 2004;26(5):680‐93.

Tan 2004a {published and unpublished data}

Tan MH, Johns D, Strand J, Halse J, Madsbad S, Eriksson JW, et al. Sustained effects of pioglitazone vs. glibenclamide on insulin sensitivity, glycaemic control, and lipid profiles in patients with type 2 diabetes. Diabetic Medicine 2004;21(8):859‐66.

Tan 2005 {published data only}

Tan MH, Baksi A, Krahulec B, Kubalski P, Stankiewicz A, Urquhart R, et al. Comparison of pioglitazone and gliclazide in sustaining glycemic control over 2 years in patients with type 2 diabetes. Diabetes Care 2005;28(3):544‐50. [PUBMED: 15735185]

Tang 2004 {published data only}

Tang JZ, Mao JP, Yang ZF, Zhou ZG, Tang WL, Feng Q. Effects of glimepiride and metformin on free fatty acid in patients with Type 2 diabetes mellitus. Zhong nan da xue xue bao. Yi xue ban [Journal of Central South University. Medical Sciences] 2004;29(6):631‐4.

Teramoto 2007 {published data only}

Teramoto T, Yamada N, Shirai K, Saito Y. Effects of pioglitazone hydrochloride on Japanese patients with type 2 diabetes mellitus. Journal of Atherosclerosis and Thrombosis 2007;14(2):86‐93.

Tessier 1999 {published data only}

Tessier D, Maheux P, Khalil A, Fülöp T. Effects of gliclazide versus metformin on the clinical profile and lipid peroxidation markers in type 2 diabetes. Metabolism: Clinical and Experimental 1999;48(7):897‐903.

Tosi 2003 {published and unpublished data}

Tosi F, Muggeo M, Brun E, Spiazzi G, Perobelli L, Zanolin E, et al. Combination treatment with metformin and glibenclamide versus single‐drug therapies in type 2 diabetes mellitus: a randomized, double‐blind, comparative study. Metabolism: Clinical and Experimental 2003;52(7):862‐7.

UGDP 1970 {published data only}

The University Group Diabetes Program. A study of the effects of hypoglycemic agents on vascular complications in patients with adult‐onset diabetes. I. Design, methods and baseline results. Diabetes 1970;19(2):747‐83.
The University Group Diabetes Program. A study of the effects of hypoglycemic agents on vascular complications in patients with adult‐onset diabetes. II. Mortality results. Diabetes 1970;19:789‐830. [PUBMED: 4926376]
The University Group Diabetes Program. A study of the effects of hypoglycemic agents on vascular complications in patients with adult‐onset diabetes. VI. Supplementary report on nonfatal events in patients treated with tolbutamide. Diabetes 1976;25:1129‐53.

UKPDS 1998 {published data only}

Clarke PM, Gray AM, Briggs A, Stevens RJ, Matthews DR, Holman RR, et al. Cost‐utility analyses of intensive blood glucose and tight blood pressure control in type 2 diabetes (UKPDS 72). Diabetologia 2005;48(5):868‐77.
Matthews DR, Cull CA, Stratton IM, Holman RR, Turner RC. UKPDS 26: Sulphonylurea failure in non‐insulin‐dependent diabetic patients over six years. Diabetic Medicine 1998;15(4):297‐303.
Mehta Z, Cull C, Stratton I, Yudkin J, Jenkinson C, Fletcher A, et al. Quality of life in type 2 diabetic patients is affected by complications but not by intensive policies to improve blood glucose or blood pressure control (UKPDS 37). Diabetes Care 1999;22(7):1125‐36.
Turner RC, Holman RR, Mathews DR, Oakes SF, Bassett PA, Stratton IM, et al. UK Prospective Diabetes Study (UKPDS). VIII. Study design, progress and performance. Diabetologia 1991;34(12):877‐90.
UK Prospective Diabetes Study Group. Intensive blood‐glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352(9131):837‐53.
UK Prospective Diabetes Study Group. United Kingdom Prospective Diabetes Study (UKPDS) 13: Relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non‐insulin dependent diabetes followed for three years. BMJ (Clinical research ed.) 1995;310(6972):83‐8. [PUBMED: 7833731]
Wright A, Burden AC, Paisey RB, Cull CA, Holman RR, UK Prospective Diabetes Study. Sulphonylurea inadequacy: efficacy of addition of insulin over 6 years in patients with type 2 diabetes in the U.K. Prospective Diabetes Study (UKPDS 57). Diabetes Care 2002;25(2):330‐6.

UKPDS 34 1998 {published data only}

Turner RC, Holman RR, Mathews DR, Oakes SF, Bassett PA, Stratton IM, et al. UK Prospective Diabetes Study (UKPDS). VIII. Study design, progress and performance. Diabetologia 1991;34(12):877‐90.
UK Prospective Diabetes Study Group. Effect of intensive blood‐glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352(9131):854‐65. [PUBMED: 9742977]
UK Prospective Diabetes Study Group. United Kingdom Prospective Diabetes Study (UKPDS) 13: Relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non‐insulin dependent diabetes followed for three years. BMJ (Clinical research ed.) 1995;310(6972):83‐8. [PUBMED: 7833731]

van de Laar 2004 {published and unpublished data}

van de Laar FA, Lucassen PLBJ, Kemp J, Van De Lisdonk EH, Van Weel C, Rutten GEHM. Is acarbose equivalent to tolbutamide as first treatment for newly diagnosed type 2 diabetes in general practice?: A randomised controlled trial. Diabetes Research and Clinical Practice 2004;63(1):57‐65.

Watanabe 2005 {published data only}

Watanabe I, Tani S, Anazawa T, Kushiro T, Kanmatsuse K. Effect of pioglitazone on arteriosclerosis in comparison with that of glibenclamide. Diabetes Research and Clinical Practice 2005;68(2):104‐10.

Wolffenbuttel 1989 {published data only}

Wolffenbuttel BH, Weber RF, van Koetsveld PM, Weeks L, Verschoor L. A randomized crossover study of sulphonylurea and insulin treatment in patients with type 2 diabetes poorly controlled on dietary therapy. Diabetic Medicine 1989;6(6):520‐5.

Wolffenbuttel 1999 {published and unpublished data}

Wolffenbuttel BH, Landgraf R. A 1‐year multicenter randomized double‐blind comparison of repaglinide and glyburide for the treatment of type 2 diabetes. Dutch and German Repaglinide Study Group. Diabetes Care 1999;22(3):463‐7.

Yamanouchi 2005 {published data only}

Yamanouchi T, Sakai T, Igarashi K, Ichiyanagi K, Watanabe H, Kawasaki T. Comparison of metabolic effects of pioglitazone, metformin, and glimepiride over 1 year in Japanese patients with newly diagnosed type 2 diabetes. Diabetic Medicine 2005;22(8):980‐5.

Zhang 2005 {published data only}

Zhang YN, Cui C, Chang ML, Wu W, Yu WG, Liu FC, Tan N, Zhang JC. Interventional effects of rosiglitazone in type 2 diabetes elderly male patients combined with atherosclerosis. Chinese Journal of Clinical Rehabilitation 2005;9(39):58‐61.

References to studies excluded from this review

Ir a:

Adetuyibi 1977 {published data only}

Adetuyibi A, Ogundipe O. A comparative trial of glipizide, glibenclamide and chlorpropamide in the management of maturity‐onset diabetes mellitus in Nigerians. Current Therapeutic Research Clinical and Experimental 1977;21(4):485.

Adlung 1974 {published data only}

Adlung J, Koch CD. Influence of tolbutamide on serum glucose level, specific activity of glucose and glucose oxidation in severe diabetes. International Journal of Clinical Pharmacology, Therapy and Toxicology 1974;10(2):128‐35. [PUBMED: 4448554]

Ahuja 1973 {published data only}

Ahuja MM, Gupta SP, Sehgel VK. Efficacy of glibenclamide in maturity‐onset diabetics as maintenance therapy. Hormone and Metabolic Research 1973;5(3):160‐3. [PUBMED: 4197503]

Akanuma 1988 {published data only}

Akanuma Y, Kosaka K, Kanazawa Y, Kasuga M, Fukuda M, Aoki S. Long‐term comparison of oral hypoglycemic agents in diabetic retinopathy. Gliclazide vs. other sulfonylureas. Diabetes Research and Clinical Practice 1988;5(2):81‐90. [PUBMED: 3416710]

Almer 1984 {published data only}

Almer LO. Effect of chloropropamide and gliclazide on plasminogen activator activity in vascular walls in patients with maturity onset diabetes. Thrombosis Research 1984;35(1):19‐25.

Aman 1977 {published data only}

Aman M, Jawad F, Sultana S, Waiz‐ul‐Haq, Nanji R. Clinical trial with glipizide in uncomplicated maturity onset diabetes mellitus. JPMA ‐ Journal of the Pakistan Medical Association 1977;27(3):293‐5.

Baba 1983 {published data only}

Baba S, Nakagawa S, Takebe K, Goto Y, Maezawa H, Takeda R, et al. Double‐blind randomized control study with gliclazide. Rinsho Hyoka (Clinical Evaluation) 1983;11(1):51‐94.

Balabolkin 1983 {published data only}

Balabolkin MI, Morozova TP, Zhizhina SA, Novikova NV, Nepsha VD. The effect of diamicron on various blood coagulation indices in patients with type II diabetes mellitus [Vliianie diamikrona na nekotorye pokazateli svertyvaiushchei sistemy krovi u bol'nykh sakharnym diabetom II tipa.]. Klinicheskaia Meditsina 1983;61(4):66‐8. [PUBMED: 6865293]

Balabolkin 1988 {published data only}

Balabolkin MI, Nedosugova LV. Effect of long‐term therapy with sulfanylurea preparations on the relation of insulin secretion and the insulin‐binding capacity of its receptors. Terapevticheskii Arkhiv 1988;60(12):91‐6.

Banerji 1995 {published data only}

Banerji MA, Chaiken RL, Lebovitz HE. Prolongation of near‐normoglycemic remission in black NIDDM subjects with chronic low‐dose sulfonylurea treatment. Diabetes 1995;44(4):466‐70.

BARI 2009 {published data only}

BARI 2D Study Group. A randomized trial of therapies for type 2 diabetes and coronary artery disease. New England Journal of Medicine 2009;360(24):2503‐15.

Bellomo 2011 {published data only}

Bellomo DA, Stefanelli G, Laviola L, Giorgino R, Giorgino F. Nateglinide provides tighter glycaemic control than glyburide in patients with type 2 diabetes with prevalent postprandial hyperglycaemia. Diabetic Medicine2011; Vol. 28, issue 5:560‐6.

Belovalova 1990 {published data only}

Belovalova IM, Gamburtseva TD, Kniazeva AP, Matveeva LS, Starosel'tseva LK. The nature of the pancreatic hormone secretion and of the metabolic indices during the acute and chronic administration of peroral hypoglycemic preparations. Problemy Endokrinologii1990; Vol. 36, issue 1:14‐20.

Ben 1988 {published data only}

Ben Khelifa F, Sellami S, Abid M, Fitouhi B, Jerbi A, Jedidi S, et al. Comparison of the hypoglycemic effect of 2 presentations‐‐of glibenclamide. La Tunisie Medicale 1988;66(12):887‐93.

Berber 1982 {published data only}

Berber MJ, Tomkin GH. The effects of gliclazide in diabetes: a comparison with tolbutamide. Irish Journal of Medical Science 1982;151(2):46‐9.

Bernas 1992 {published data only}

Bernas M, Czech A, Taton J. Relative effectiveness of tolbutamide, chlorpropamide and gliclazide. Polski Tygodnik Lekarski1992; Vol. 47, issue 1‐2:35‐9.

Berry 1981 {published data only}

Berry EM, Bar‐On H. Comparison of sulphonylurea and insulin treatment on lipid levels in maturity‐onset diabetic men and women. Israel Journal of Medical Sciences1981; Vol. 17, issue 5:384‐7.

Blumenbach 1976 {published data only}

Blumenbach L, Kiesselbach N, Lehnert J. Further results of a multi‐centre clinical trial with the oral antidiabetic drug glisoxepide [Neue Ergebnisse einer multizentrischen klinischen Studie mit dem oralen Antidiabetikum Glisoxepid]. Arzneimittel‐Forschung 1976;26(5):931‐43.

Bruns 1990 {published data only}

Bruns W, Jutzi E, Staritz B, Willkommen G, Willkommen G. Treatment of type II diabetics (non‐insulin‐dependent) for sulphonylurea secondary failure ‐ combined therapy, using glibenclamid and insulin. Zeitschrift fur Klinische Medizin 1990;45(11):983‐6.

Calvagno 1983 {published data only}

Calvagno M, Acacia E, Kremer P, Marowsky C, Maccione E, Taddey N, et al. Clinical and biomedical study of a sulphonylurea hypoglycemic agent with action at vascular level [Estudio clinico y biomedico de un hipoglucemiante sulfonilureico con accion a nivel vascular]. Semana Médica 1983;162(20):799‐808.

Cefalu 1998 {published data only}

Cefalu WT, Bell‐Farrow A, Wang ZQ, McBride D, Dalgleish D, Terry JG. Effect of glipizide GITS on insulin sensitivity, glycemic indices, and abdominal fat composition in NIDDM. Drug Development Research 1998;44(1):1‐7.

Ceriello 2005 {published data only}

Ceriello A, Johns D, Widel M, Eckland DJ, Gilmore KJ, Tan MH. Comparison of effect of pioglitazone with metformin or sulfonylurea (monotherapy and combination therapy) on postload glycemia and composite insulin sensitivity index during an oral glucose tolerance test in patients with type 2 diabetes. Diabetes Care 2005;28(2):266‐72.

Chan 1982 {published data only}

Chan TK, Chan V, Teng CS, Yeung RTT. Effects of gliclazide and glibenclamide on platelet function, fibrinolysis and metabolic control in diabetic patients with retinopathy. Semaine des Hopitaux 1982;58(19):1197‐200.

Chandra 2008 {published data only}

Chandra ST, Priya G, Khurana ML, Jyotsna VP, Sreenivas V, Dwivedi S, et al. Comparison of gliclazide with insulin as initial treatment modality in newly diagnosed type 2 diabetes. Diabetes Technology & Therapeutics 2008;10(5):363‐8. [PUBMED: 18715212]

Chen 1987 {published data only}

Chen H. Pharmacokinetic and clinical study on glibenclamide. Zhonghua Yi Xue Za Zhi 1987;67(10):533‐5.

Cortinovis 1998 {published data only}

Cortinovis A, Crippa A, Sciacca V, Caravaggio V, Crippa M. [Modificazioni emoreologiche, metaboliche ed emocogulative in diabetici in trattamento con sulfaniluree]. Minerva Medica 1998;79(5):391‐8.

Derosa 2010 {published data only}

Derosa G, Maffioli P, Salvadeo SAT, Ferrari I, Ragonesi PD, Querci F, et al. Exenatide versus glibenclamide in patients with diabetes. Diabetes Technology and Therapeutics 2010;12(3):233‐40.

Dills 1996 {published data only}

Dills DG, Schneider J. Clinical evaluation of glimepiride versus glyburide in NIDDM in a double‐blind comparative study. Glimepiride/Glyburide Research Group. Hormone and Metabolic Research1996; Vol. 28, issue 9:426‐9. [PUBMED: 8911977]

Dowey 1979 {published data only}

Dowey KE, Grant AP, Hayes JR. Glipizide evaluation after a one year trial in maturity onset diabetics. Ulster Medical Journal 1979;48(1):65‐8.

Drouin 2000 {published data only}

Drouin P. Diamicron MR once daily is effective and well tolerated in type 2 diabetes: a double‐blind, randomized, multinational study. Journal of Diabetes & its Complications 2000;14(4):185‐91.

Drouin 2004 {published data only}

Drouin P, Standl E, Diamicron MR. Gliclazide modified release: results of a 2‐year study in patients with type 2 diabetes. Diabetes, Obesity & Metabolism 2004;6(6):414‐21.

Duprey 1971 {published data only}

Duprey J, Lubetzki J. Insulin secretion in maturity‐onset diabetes mellitus. Effects of the prolonged administration of glybutamide [L'insulino‐secretion dans le diabete de la maturite. Effets de l'administration prolongee de glybutamide.]. La Presse Medicale 1971;79(54):2469‐71. [PUBMED: 5157896]

Engelhardt 1965 {published data only}

Engelhardt HT, Vecchio TJ. The long‐term effect of tolbutamide on glucose tolerance in adult, asymptomatic, latent diabetics. Metabolism1965; Vol. 14:885‐90.

Ferner 1991 {published data only}

Ferner RE, Antsiferov ML, Kelman AW, Alberti KGMM, Rawlins MD. The relationships between dose and concentration of tolbutamide and insulin and glucose responses in patients with non‐insulin‐dependent diabetes. European Journal of Clinical Pharmacology1991; Vol. 40, issue 2:163‐8.

Forst 2011 {published data only}

Forst T, Weber M, Pfützner A, Löbig M, Hohberg C, Fuchs W. C‐peptide and intima media thickness in type 2 diabetes mellitus treated with pioglitazone. Diabetes Stoffwechsel Und Herz2011; Vol. 20, issue 2.

Fuchs 1973 {published data only}

Fuchs K. Glipizide versus tolbutamide in maturity‐onset diabetes, an open comparative study. Diabetologia 1973;9(Suppl):351‐5.

Garber 2002 {published data only}

Garber AJ, Bruce S, Fiedorek FT. Durability of efficacy and long‐term safety profile of glyburide/metformin tablets in patients with type 2 diabetes mellitus: an open‐label extension study. Clinical Therapeutics 2002;24(9):1401‐13.
Garber AJ, Larsen J, Schneider SH, Piper BA, Henry D, Glyburide/Metformin Initial Therapy Study. Simultaneous glyburide/metformin therapy is superior to component monotherapy as an initial pharmacological treatment for type 2 diabetes. Diabetes, Obesity & Metabolism 2002;4(3):201‐8.

Garber 2003 {published data only}

Garber AJ, Donovan DS, Dandona P, Bruce S, Park JS. Efficacy of glyburide/metformin tablets compared with initial monotherapy in type 2 diabetes. Journal of Clinical Endocrinology & Metabolism 2003;88(8):3598‐604.

Gargiolo 2001 {published data only}

Gargiulo P, Caccese D, Pignatelli P, Brufani C, De Vito F, Marino R, et al. Metformin decreases platelet superoxide anion production in diabetic patients. Diabetes/Metabolism Research and Reviews2001; Vol. 18, issue 2:156‐9.

Giles 2008 {published data only}

Giles TD, Miller AB, Elkayam U, Bhattacharya M, Perez A. Pioglitazone and heart failure: results from a controlled study in patients with type 2 diabetes mellitus and systolic dysfunction. Journal of Cardiac Failure 2008;14(6):445‐52.

Giles 2010 {published data only}

Giles TD, Elkayam U, Bhattacharya M, Perez A, Miller AB. Comparison of pioglitazone vs glyburide in early heart failure: insights from a randomized controlled study of patients with type 2 diabetes and mild cardiac disease. Congestive Heart Failure 2010;16(3):111‐7.

Goldberg 1996 {published data only}

Goldberg RB, Holvey SM, Schneider J, Bansal S, Blonde L, Boden G, et al. A dose‐response study of glimepiride in patients with niddm who have previously received sulfonylurea agents. Diabetes Care 1996;19(8):849‐56.

Groop 1989 {published data only}

Groop L, Widén E, Franssila‐Kallunki A, Ekstrand A, Saloranta C, Schalin C, et al. Different effects of insulin and oral antidiabetic agents on glucose and energy metabolism in type 2 (non‐insulin‐dependent) diabetes mellitus. Diabetologia 1989;32(8):599‐605.

Gudat 1998 {published data only}

Gudat U, Bungert S, Kemmer F, Heinemann L. The blood glucose lowering effects of exercise and glibenclamide in patients with type 2 diabetes mellitus. Diabetic Medicine 1998;15(3):194‐8.

Gurling 1970 {published data only}

Gurling KJ. A comparison of glibenclamide with chlorpropamide in newly diagnosed maturity‐onset diabetes. Postgraduate Medical Journal 1970;Suppl:66‐9.

Happ 1974 {published data only}

Happ J, Beyer J, Nest E, Fröhlich A, Althoff PH, Schöffling K. Blood sugar, serum insulin, nonesterified fatty acids and somatotropin in daily profile in adult diabetics under monotherapy with various sulfonylureas [Blutzucker, Seruminsulin, unveresterte Fettsäuren und Wachstumshormon im Tagesprofil bei Erwachsenen‐Diabetikern unter Monotherapie mit verchiedenen Sulfonylharnstoffen]. Arzneimittel‐Forschung 1974;24(8):1228‐34.

Haupt 1974 {published data only}

Haupt E, Beyer J, Schoffling K. The influence of various sulphonylurea derivatives on the oral glucose‐tolerance tests in healthy subjects and obese and maturity‐onset diabetics (author's transl) [German]. Deutsche Medizinische Wochenschrift 1974;99(9):385‐8.

Hollander 2001 {published data only}

Hollander PA, Schwartz SL, Gatlin MR, Haas SJ, Zheng H, Foley JE, et al. Importance of early insulin secretion: comparison of nateglinide and glyburide in previously diet‐treated patients with type 2 diabetes. Diabetes Care 2001;24(6):983‐8.

Howes 2000 {published data only}

Howes LG. Cardiovascular effects of sulphonylureas: role of K(ATP) channels. Diabetes, Obesity and Metabolism2000; Vol. 2, issue 2:67‐73.

Hristov 2002 {published data only}

Hristov V, Sheinkova G, Simeonov S, Botushanov N, Valkov Y, Tzinlikov I. Clinical assessment of glimepiride (Amaril) in the treatment of type 2 diabetes mellitus patients (results of a multicenter study). Endocrinologia 2002;7(1):30‐5.

Hussain 2007 {published data only}

Hussain SA. Silymarin as an adjunct to glibenclamide therapy improves long‐term and postprandial glycemic control and body mass index in type 2 diabetes. Journal of Medicinal Food 2007;10(3):543‐7. [PUBMED: 17887949]

Inukai 2005 {published data only}

Inukai K, Watanabe M, Nakashima Y, Sawa T, Takata N, Tanaka M, et al. Efficacy of glimepiride in Japanese type 2 diabetic subjects. Diabetes Research and Clinical Practice 2005;68(3):250‐7. [PUBMED: 15936468]

Irsigler 1979 {published data only}

Irsigler K, Ogris E, Steinhardt T, Brandle J, Regal H, Zdolsek I. Comparison of glibenclamide, gliquidone, glisoxepide and placebo in maturity onset diabetics of differing degrees of severity (author's transl) [German]. Wiener Klinische Wochenschrift 1979;91(16):541‐50.

Ishizuka 1994 {published data only}

Ishizuka T, Taniguchi O, Yamamoto M, Kajita K, Nagashima T, Takeda N, et al. Thrombin‐induced platelet aggregation, phosphoinositide metabolism and protein phosphorylation in NIDDM patients treated by diet, sulphonylurea or insulin. Diabetologia 1994;37(6):632‐8.

Jackson 1969 {published data only}

Jackson WP, Vinik AI. Preliminary trial of a powerful new sulphonylurea in maturity‐onset diabetes‐HB419 (glibenclamide). South African Medical Journal 1969;43(32):1002‐4.

Jerums 1987 {published data only}

Jerums G, Murray RML, Seeman E. Lack of effect of gliclazide on early diabetic nephropathy and retinopathy: a two‐year controlled study. Diabetes Research and Clinical Practice 1987;3(2):71‐80.

Johnston 1970 {published data only}

Johnston AT, Ireland JT. A comparison of glibenclamide and chlorpropamide in the treatment of non‐obese maturity onset diabetics. Postgraduate Medical Journal 1970;December(Suppl):98‐100. [PUBMED: 5500517]

Josephkutty 1990 {published data only}

Josephkutty S, Potter JM. Comparison of tolbutamide and metformin in elderly diabetic patients. Diabetic Medicine 1990;7(6):510‐4.

Joshi 2002 {published data only}

Joshi A, Gupta BS, Sharma SK, Singh V, Chaturvedi MK, Singhal A, et al. Comparative study of repaglinide with glibenclamide in the management of type 2 diabetes mellitus [abstract no: 12]. Journal of the Association of Physicians of India2002; Vol. 50.

Kakhnovskii 1993 {published data only}

Kakhnovskii IM, Koroleva TV, Zakharchenko VN, Larionov SN. A comparative evaluation of the effect of glurenorm and sulfonylurea preparations on the intravascular microcirculatory indices in type‐II diabetes mellitus. Problemy Endokrinologii 1993;39(2):7‐9.

Kanoun 1996 {published data only}

Kanoun F, Ben Rehaiem B, Mekaouar A, Abdennebi E, Ftouhi B, Idriss S, et al. Secondary failure of oral hypoglycaemic agents (OHA) in the treatment of non insulin‐dependent diabetic (NIDDM) patients: effects of carbohydrate and caloric restrictive diet. Revue Francaise d'Endocrinologie Clinique ‐ Nutrition et Metabolisme 1996;37(6):529‐36.

Langenfeld 2005 {published data only}

Langenfeld MR, Forst T, Hohberg C, Kann P, Lübben G, Konrad T, et al. Pioglitazone decreases carotid intima‐media thickness independently of glycemic control in patients with type 2 diabetes mellitus: results from a controlled randomized study. Circulation 2005;111(19):2525‐31.

Lecomte 1977 {published data only}

Lecomte MJ, Luyckx AS, Lefebvre PJ. Plasma glucagon and clinical control of maturity‐onset type diabetes. Effects of diet, placebo and glipizide. Diabete et Metabolisme 1977;3(4):239‐43. [340296]

Levy 1995 {published data only}

Levy J, Vandenberg M, Grunberger G. Insulin versus glipizide treatment in patients with non‐insulin‐dependent diabetes mellitus. Effects on blood pressure and glucose tolerance. American Journal of Hypertension 1995;8(5 Pt 1):445‐53.

Li 2009 {published data only}

Li H, Li W, Gu Y, Han Y, Wang J, Xu B, et al. Comparison of continual insulin or secretagogue treatment in type 2 diabetic patients with alternate insulin‐secretagogue administration. [Erratum appears in Diabetes Res Clin Pract. 2009 Sep;85(3):342]. Diabetes Research & Clinical Practice 2009;84(2):158‐62.

Lim 1970 {published data only}

Lim P, Khoo OT. Metformin compared with tolbutamide in the treatment of maturity‐onset diabetes mellitus. Medical Journal of Australia 1970;1(6):271‐3.

Lindbjerg 1976 {published data only}

Lindbjerg IF, Christoffersen EM, Kuusisto A, Lodahl K, Sagild U, Sterling N, et al. Clinical comparison between glibornuride (Glutril) and tolbutamide in maturity‐onset diabetes: a controlled double‐blind trial. Current Therapeutic Research, Clinical and Experimental 1976;20(3):277‐82.

Liu 1985 {published data only}

Liu GC, Coulston AM, Lardinois CK, Hollenbeck CB, Moore JG, Reaven GM. Moderate weight loss and sulfonylurea treatment of non‐insulin‐dependent diabetes mellitus. Combined effects. Archives of Internal Medicine 1985;145(4):665‐9.

Lomuscio 1994 {published data only}

Lomuscio A, Vergani D, Marano L, Castagnone M, Fiorentini C. Effects of glibenclamide on ventricular fibrillation in non‐insulin‐dependent diabetics with acute myocardial infarction. Coronary Artery Disease 1994;5(9):767‐71.

Mafauzy 2002 {published data only}

Mafauzy M. Repaglinide versus glibenclamide treatment of type 2 diabetes during Ramadan fasting. Diabetes Research & Clinical Practice 2002;58(1):45‐53.

Mazzone 2006 {published data only}

Mazzone T, Meyer PM, Feinstein SB, Davidson MH, Kondos GT, D Ágostino RB, et al. Effect of pioglitazone compared with glimepiride on carotid intima‐media thickness in type 2 diabetes: a randomized trial. JAMA 2006;296(21):2572.

Meneilly 2011 {published data only}

Meneilly GS. Effect of repaglinide versus glyburide on postprandial glucose and insulin values in elderly patients with type 2 diabetes. Diabetes Technology and Therapeutics 2011;13(1):63‐5.

Mogensen 1976 {published data only}

Mogensen EF, Worm J, Mikkelsen BO. Clinical comparison between glibornuride (Glutril) and glibenclamide in maturity‐onset diabetes: a controlled double‐blind trial. Current Therapeutic Research, Clinical and Experimental 1976;19(6):559‐64.

Nakamura 2000 {published data only}

Nakamura T, Ushiyama C, Shimada N, Hayashi K, Ebihara I, Koide H. Comparative effects of pioglitazone, glibenclamide, and voglibose on urinary endothelin‐1 and albumin excretion in diabetes patients. Journal of Diabetes and Its Complications 2000;14(5):250‐4.

Nikkilä 1982 {published data only}

Nikkilä K, Groop L. Glibenclamide and gliquidone in the treatment of non‐insulin‐dependent diabetes mellitus. Acta Medica Scandinavica 1982;211(1‐2):13‐7.

Nissen 2008 {published data only}

Nissen SE, Nicholls SJ, Wolski K, Nesto R, Kupfer S, Perez A, et al. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA2008; Vol. 299, issue 13:1561‐73. [PUBMED: 18378631]

Noury 1991 {published data only}

Noury J, Nandeuil A. Comparative three‐month study of the efficacies of metformin and gliclazide in the treatment of NIDD. Diabète & Métabolisme 1991;17(1 Pt 2):209‐12.

Omrani 2005 {published data only}

Omrani GHR, Lari OB, Mehdizadeh AR, Zare N, Saadat N. Comparison of serum homocysteine level in metformin versus glibenclamide treated type 2 DM patients. Iranian Journal of Diabetes and Lipid Disorders2005; Vol. 4, issue 2:E4+E4i‐viii.

Osei 2003 {published data only}

Osei K, Rhinesmith S, Gaillard T, Schuster D. Metabolic effects of chronic glipizide gastrointestinal therapeutic system on serum glucose, insulin secretion, insulin sensitivity, and hepatic insulin extraction in glucose‐tolerant, first‐degree relatives of African American patients with type 2 diabetes: new insights on mechanisms of action. Metabolism: Clinical and Experimental 2003;52(5):565‐72.

Papa 2006 {published data only}

Papa G, Fedele V, Rizzo MR, Fioravanti M, Leotta C, Solerte SB, et al. Safety of type 2 diabetes treatment with repaglinide compared with glibenclamide in elderly people: a randomized, open‐label, two‐period, cross‐over trial. Diabetes Care 2006;29(8):1918‐20.

Perez 2006 {published data only}

Perez A, Spanheimer R, Khan M. Glycaemic control in patients with type 2 diabetes: the effects of pioglitazone vs glyburide in a 3‐year randomized double‐blind trial. Diabetologia 2006;49:0807.

Quatraro 1990 {published data only}

Quatraro A, Consoli G, Magno M, Caretta F, Nardozza A, Ceriello A, et al. Hydroxychloroquine in decompensated, treatment‐refractory noninsulin‐dependent diabetes mellitus. A new job for an old drug?. Annals of Internal Medicine 1990;112(9):678‐81.

Rao 2010 {published data only}

Rao VU, Alokozai D, Voloshko P, Schiller NB. Effect of the dual peroxisome proliferator‐activated receptor alpha/gamma agonist, muraglitazar, on cardiac structure and function in type 2 diabetic patients. Journal of the American College of Cardiology. 2010; Vol. Conference: American College of Cardiology's 59th Annual Scientific Session and i2 Summit: Innovation in Intervention Atlanta, GA United States.

RECORD {published data only}

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Rosenstock J, Corrao PJ, Goldberg RB, Kilo C. Diabetes control in the elderly: a randomized, comparative study of glyburide versus glipizide in non‐insulin‐dependent diabetes mellitus. Clinical Therapeutics 1993;15(6):1031‐40.

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Rupprecht E, Konig E, Limmer J. Clinical evaluation of gliquidone‐short acting sulfonylurea derivative‐comparison with glibenclamide and gliclazide. Polski Tygodnik Lekarski 1993;48(Suppl 1):31‐2.

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Sasahara T, Jerums G, Nestel P. Effects of insulin therapy and glycemic control on distribution of HDL alpha and pre‐beta subfractions in non insulin‐dependent diabetic subjects. Nutrition, Metabolism, and Cardiovascular Diseases 1999;9(1):19‐24.

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Schernthaner G, Grimaldi A, Di Mario U, Drzewoski J, Kempler P, Kvapil M, et al. GUIDE study: double‐blind comparison of once‐daily gliclazide MR and glimepiride in type 2 diabetic patients. European Journal of Clinical Investigation2004; Vol. 34, issue 8:535‐42.

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Tovi J, Svanborg E, Nilsson BY, Engfeldt P. Diabetic neuropathy in elderly type 2 diabetic patients: effects of insulin treatment. Acta Neurologica Scandinavica 1998;98(5):346‐53.

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Toyota T, Fukao A, Kaneko T, Suda T, Maruhama Y, Sato J. Clinical Evaluation of glimepiride (HOE490) in non‐insulin‐dependent diabetes mellitus: a double‐blind placebo‐controlled study/phase III additional study. Rinsho Iyaku (Journal of Clinical Therapeutics and Medicines) 1997;13(17):4457‐78.

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Tsumura K. Clinical evaluation of glimepiride (HOE490) in NIDDM, including a double blind comparative study versus gliclazide. Diabetes Research and Clinical Practice 1995;28 Suppl:147‐9.

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Zhou, W. 60 cases of type II diabetes mellitus treated by Zishen Jiangtang decoction compared with 25 cases treated by glibenclamide in the control group. Zhejiang Journal of Traditional Chinese Medicine [Zhe Jiang Zhong Yi Za Zhi]1999, issue 8:328.

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

Abbatecola 2006

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: blinding not described, but we assume open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: repaglinide

Participants

INCLUSION CRITERIA:

  • T2DM

  • treatment‐naive

  • 60 to 78 years

EXCLUSION CRITERIA:

  • severe macro‐ and microangiopathy

  • coronary heart disease

  • heart failure

  • medium/severe hypertension

  • cancer

  • chronic obstructive pulmonary disease

  • upper limb paresis or paralysis

  • dementia

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: NR

COUNTRY/LOCATION: Italy

SETTING: outpatients

TREATMENT BEFORE STUDY: diet and exercise

TITRATION PERIOD: titrated during trial

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, FPG, postprandial glucose, cognition score, adverse events, hypoglycaemic episodes, Homeostasis Model of Assessment ‐ Insulin Resistance, blood pressure, biochemical variables, carotid ultrasound, depression

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 12 months + 3 weeks

DURATION OF FOLLOW‐UP: 12 months + 3 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING: NR

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "We tested the hypothesis that an elevated PPG instability could be associated with both global cognitive functioning as well as executive and attention functioning neuropsychological tests."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "After patient referral to our offices, participants who accepted to enroll in the study were randomly assigned to undergo monotherapy with repaglinide (initially started with 1 mg twice a day) or glibenclamide therapy (also known as glyburide in the United States and Canada; initially started with 2.5 mg twice a day)."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Blinding not described, but we assume open‐label

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Quote: "All MRI evaluations were made by physicians not involved in the study and blind toward the study design."

Blinding of participants for the other outcomes are not described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss to follow‐up adequately described

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Unclear risk

Funding not reported

Trials according to risk of bias

Unclear risk

Adequate sequence generation and allocation concealment, inadequate blinding
ADOPT 2006

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control 1: rosiglitazone

Control 2: metformin

Participants

INCLUSION CRITERIA:

  • T2DM within the last 3 years

  • 30 to 75 years

  • previously diet/exercise (exceptions: prior insulin use for gestational diabetes, short‐term (≤1 months) insulin use to maintain glycaemic control for hospitalisation, medical procedure, or intervention; and ≤1 month use of any oral hypoglycaemic agent at least 2 months before screening)

  • FPG 7 to 13 mmol/L at screening and 7 to 10 mmol/L at randomisation

EXCLUSION CRITERIA:

  • clinically significant hepatic disease

  • alanine aminotransferase ≥2.5 times the upper limit of the normal reference range

  • renal impairment indicated by serum creatinine concentration

  • anaemia

  • history of lactate acidosis

  • unstable or severe angina

  • congestive heart failure

  • uncontrolled hypertension

  • any chronic disease requiring continuous intermittent treatment with corticosteroids

  • any associated condition that could preclude completion of the study

  • active drug or alcohol abuse within the last 6 months

  • patients with variation in body weight ≥ 5% during the run‐in period will also be excluded

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: 247

Control 1: 231

Control 2: 269

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR/753/370

Control 1: NR/744/378

Control 2: NR/737/377

Interventions

NUMBER OF STUDY CENTRES: 488

COUNTRY/LOCATION: North America, Europe and Canada

SETTING: outpatients

TREATMENT BEFORE STUDY: lifestyle interventions

TITRATION PERIOD: titrated during trial

GLYCAEMIC TARGET: FPG below 140 mg/dl (7.8 mmol/L)

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): time to monotherapy failure, glycaemic control, islet beta‐cell function, insulin sensitivity, progression of microalbuminuria, fibrinolytic markers, cardiovascular risk factors, renal function, health status, quality of life and safety parameters

Study details

RUN‐IN PERIOD: 4 weeks

DURATION OF INTERVENTION: 4 years

DURATION OF FOLLOW‐UP: 4 years

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "Our goal was to evaluate, in patients recently diagnosed with type 2 diabetes (<3 years), the long term efficacy of monotherapy with rosiglitazone on glycemic control and on the progression of pathophysiological abnormalities associated with type 2 diabetes as compared with metformin or glyburide monotherapy."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Randomization was performed centrally and was concealed and stratified according to the sex of the patients in blocks of six."

Allocation concealment (selection bias)

Low risk

Quote: "Randomization was performed centrally and was concealed and stratified according to the sex of the patients in blocks of six."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "All study medication will be supplied in capsules of identical size and color, and all patients will take the same number of capsules each day."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "A central laboratory will be used during the study. Samples will be collected and transferred under appropriate conditions to the central laboratory."

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All loss to follow‐up adequately described

Selective reporting (reporting bias)

Low risk

All predefined primary and secondary outcomes in the protocol are assessed

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Low risk

Adequate sequence generation, allocation concealment and blinding
AGEE/DCD/046/UK

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: repaglinide

Participants

INCLUSION CRITERIA:

  • T2DM

  • 40 to 75 years

  • BMI ≥ 21 and ≤ 35 kg/m2

  • HbA1c ≥ 6.5 (diet‐treated) and ≤ 10% (for patients previously on sulphonylurea)

EXCLUSION CRITERIA: NR

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 26

COUNTRY/LOCATION: United Kingdom

SETTING: outpatients

TREATMENT BEFORE STUDY: diet and/or sulphonylurea

TITRATION PERIOD: 6 to 8 weeks

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, FPG, hypoglycaemia, adverse events, lipid metabolism and beta‐cell status

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 12 months + 6 to 8 weeks

DURATION OF FOLLOW‐UP: 12 months + 6 to 8 weeks + 3 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: not published, but the synopsis describing the trial is in English. Trial identified through approval letter of the US Food and Drug Administration (FDA 2000)

COMMERCIAL FUNDING

PUBLICATION STATUS: unpublished

Stated aim of study

Quote: "..to assess and compare the effect of repaglinide and glibenclamide on glycaemic control as measured by HbA1c and fasting plasma glucose (FPG) when administered to Type 2 diabetic patients for 12 months."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "The patients were randomized to a treatment group in a 2:1 ratio of repaglinide and glibenclamide."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "Placebo: used to double‐blind the trial; encapsulated tablets, orally"

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

We assume the outcome assessors were blinded due to a double‐blind design

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All loss to follow‐up clearly described

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes assessed as predefined

Academic bias

High risk

The data for the trial are provided from Novo Nordisk

Sponsor bias

High risk

Sponsored by pharmaceutical company

Trials according to risk of bias

Unclear risk

Unclear randomisation and allocation concealment, adequate blinding
AGEE/DCD/047/B/F/I

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: gliclazide

Control: repaglinide

Participants

INCLUSION CRITERIA:

  • T2DM

  • 40 to 75 years

  • BMI ≥ 21 and ≤ 35 kg/m2

  • HbA1c ≥ 6.5 (diet‐treated) and ≤ 12% (for patients previously on sulphonylurea)

EXCLUSION CRITERIA: NR

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 41

COUNTRY/LOCATION: Belgium, France and Italy

SETTING: outpatients

TREATMENT BEFORE STUDY: diet and/or sulphonylurea

TITRATION PERIOD: 6 to 8 weeks

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, FPG, hypoglycaemia, adverse events, lipid metabolism and beta‐cell status

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 12 months + 6 to 8 weeks

DURATION OF FOLLOW‐UP: 12 months + 6 to 8 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: not published, but the synopsis describing the trial is in English. Trial identified through approval letter of the US Food and Drug Administration (FDA 2000)

COMMERCIAL FUNDING

PUBLICATION STATUS: unpublished

Stated aim of study

Quote: "..to assess and compare the effect of repaglinide and gliclazide on glycaemic control as measured by HbA1c and fasting plasma glucose (FPG) when administered to Type 2 diabetic patients for 12 months."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "The patients were randomized to a treatment group in a 2:1 ratio of repaglinide and gliclazide."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "Placebo: used to double‐blind the trial; encapsulated tablets, orally"

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

We assume the outcome assessors were blinded due to a double‐blind design

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All loss to follow‐up clearly described

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes assessed as predefined

Academic bias

High risk

The data for the trial are provided from Novo Nordisk

Sponsor bias

High risk

Sponsored by pharmaceutical company

Trials according to risk of bias

Unclear risk

Unclear randomisation and allocation concealment, adequate blinding
Alvarsson 2010

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: insulin

Participants

INCLUSION CRITERIA:

  • T2DM diagnosed < 2 years previously were asked for participation

  • women and men

  • 35 to 70 years of age

  • FBG between 7.0 and 12.0 mmol/L during screening on one occasion when on diet alone for at least 1 month

EXCLUSION CRITERIA:

  • pharmacological treatment for diabetes > 6 months

  • low fasting plasma C‐peptide concentrations (< 0.2 nmol/L)

  • ketonuria (more than trace amounts)

  • BMI > 35 kg/m2

  • plasma creatinine > 150 µmol/L

  • severe retinopathy (proliferative or preproliferative)

  • severe cardiac disease (NYHA III–IV)

  • positivity for islet antibodies (islet cell antibodies, glutamic acid decarboxylase 65 antibodies and protein tyrosine phosphatase–like protein IA‐2 antibodies)

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR/2/2

Control: NR/1/1

Interventions

NUMBER OF STUDY CENTRES: 6

COUNTRY/LOCATION: Sweden

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: titrated, but time period not reported

GLYCAEMIC TARGET: HbA1c levels within target level, that is below or equal to 1% above the upper normal level of HbA1c of 6.2%

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): retinopathy, quality of life, biochemical variables, effect on beta‐cell function

Study details

RUN‐IN PERIOD: none

DURATION OF INTERVENTION: 6 years

DURATION OF FOLLOW‐UP: 6 years

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "To compare effects of early insulin vs. glibenclamide treatment on beta‐cell function, metabolic control and quality of life (QL) in recently diagnosed patients with type 2 diabetes."

Notes

Data for participants on antihypertensives are the number on angiotensin converting enzyme inhibitor or angiotensinogen receptor blocker

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Patients were randomized to monotherapy with glibenclamide or insulin."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Open‐label design, we assume not blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Drop‐outs clearly described

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions. This trial is published in 3 publications

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Unclear sequence generation, allocation concealment, inadequate blinding
APPROACH 2010

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glipizide

Control: rosiglitazone

Participants

INCLUSION CRITERIA:

  • 30 and 80 years of age

  • established T2DM undergoing clinically indicated coronary angiography or percutaneous coronary intervention with at least one atherosclerotic plaque in a non intervened coronary artery with 10% to 50% luminal narrowing

  • treated for T2DM with diet and exercise only, oral antidiabetic monotherapy or submaximal oral antidiabetic combination therapy (≤ 50% of maximal dose for each agent)

  • screening HbA1c > 7% and ≤ 10% (if treated with diet and exercise only) or > 6.5% and ≤ 8.5% (if treated with oral antidiabetic medications)

EXCLUSION CRITERIA:

  • ST‐segment elevation myocardial infarction in the prior 30 days

  • coronary artery bypass graft surgery

  • severe cardiac valvular disease

  • left ventricular ejection fraction < 40%

  • heart failure (NYHA I‐IV)

  • uncontrolled hypertension (systolic blood pressure > 170 mm Hg or diastolic blood pressure > 100 mm Hg)

  • renal insufficiency (serum creatinine ≥ 1.5 mg/dl for men or ≥ 1.4 mg/dl for women)

  • hepatic enzyme elevation (alanine aminotransferases or aspartate aminotransferase > 2.5 × upper limit of normal or total bilirubin> 2 × upper limit of normal)

DIAGNOSTIC CRITERIA: diagnosed with T2DM, established diagnosis of T2DM based on ADA, WHO or local national guidelines

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: 339

Control: 333

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: 279/238/262

Control: 280/237/248

Interventions

NUMBER OF STUDY CENTRES: 92

COUNTRY/LOCATION: 19 (Asia, Europe, North America, South America)

SETTING: outpatients

TREATMENT BEFORE STUDY: diet or oral antidiabetics

TITRATION PERIOD: 12 weeks

GLYCAEMIC TARGET:

HbA1c < 7% (target mean daily glucose < 126 mg/dl (7.0 mmol/L))

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): per cent atheroma volume, intravascular ultrasound efficacy parameters include change in normalised total atheroma volume and change in atheroma volume within the most diseased 10 mm sub‐segment, change from baseline in vessel volume, change in biochemical variables, major adverse cardiovascular events (cardiovascular and non‐cardiovascular death, non‐fatal myocardial infarction and stroke, coronary revascularisation, and hospitalisation for recurrent myocardial ischaemia) and new or worsening heart failure

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 18.6 months

DURATION OF FOLLOW‐UP: 18.6 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "The aim of the APPROACH (Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in diabetes patients with Cardiovascular History) trial is to compare the glucose‐independent effects of the thiazolidinedione rosiglitazone with the sulfonylurea glipizide on the progression of coronary atherosclerosis, as measured by IVUS, in participants with T2DM and coronary artery disease."

Notes

Number for antihypertensive treatment is the number of participants with ACE‐inhibitor or angiotensin receptor blocker treatment. Number for lipid‐lowering treatment is the number of participants on statins.

All prior oral antidiabetic medications are down titrated by 50% at randomisation and discontinued after 1 month as double‐blind study medications were up titrated

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Participants are randomized in a 1:1 ratio to rosiglitazone or glipizide treatment using an automated voice‐response system."

Allocation concealment (selection bias)

Low risk

Quote: "Participants are randomized in a 1:1 ratio to rosiglitazone or glipizide treatment using an automated voice‐response system."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "Participants, study personnel, and core laboratory staff are blinded to treatment assignment."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "Participants, study personnel, and core laboratory staff are blinded to treatment assignment."

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All loss to follow‐up described

Selective reporting (reporting bias)

Low risk

All primary and secondary outcomes described in protocol and assessed

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from the pharmaceutical industry

Trials according to risk of bias

Low risk

Adequate sequence generation, allocation concealment and blinding
Birkeland 1994

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea 1: glibenclamide

Sulphonylurea 2: glipizide

Control: placebo

Participants

INCLUSION CRITERIA:

  • T2DM

  • non‐pharmacological treated for T2DM

  • HbA1c between 7% and 11%

  • considerable residual beta‐cell function (the C‐peptid concentration 6 min after injection of 1 mg glucagon was > 0.7 nM)

EXCLUSION CRITERIA:

  • severe concurrent illness

  • signs of chronic cardiac, hepatic, pulmonary or renal disease

DIAGNOSTIC CRITERIA: without insulin for > 1 year after diabetes diagnosis

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: Norway

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: titrated during trial to achieve target

GLYCAEMIC TARGET: FBG < 8 mmol/L and HbA1c < 7.5% without hypoglycaemia

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): glycaemic control, insulin secretion and biochemical variables

Study details

RUN‐IN PERIOD: 3 to 6 months

DURATION OF INTERVENTION: 15 months

DURATION OF FOLLOW‐UP: 15 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "The aim of the study was to assess and compare the long‐term (15 months) effects of moderate doses of glipizide and glyburide on glycaemic control and insulin secretion in a randomized placebo‐controlled double‐blind fashion."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "…they were subjected to a stratified randomisation procedure…"

Through correspondence it was clarified that the randomisation was done manually by drawing numbers

Allocation concealment (selection bias)

Low risk

Through correspondence it was clarified that the concealment was made with opaque envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "All tablets looked identical and contained either 1.75 mg glyburide, 2.5 mg glipizide, or placebo."

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Through correspondence it was clarified that the outcome assessors were not blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss to follow‐up adequately described

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes not clearly defined in the publication. However, the list of priority of outcomes was not corrected from the answer we received by correspondence

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Adequate sequence generation, allocation concealment and blinding of participants, inadequate blinding of outcome assessors

Birkeland 2002

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: insulin

Participants

INCLUSION CRITERIA:

  • T2DM

  • age of onset diabetes ≥ 35 years

  • HbA1c 7% to 10%

  • age 40 to 70 years

  • BMI < 35 kg/m2

  • duration of diabetes > 2 years without insulin treatment

  • glucagon‐stimulated peptide > 0.7 nmol/L

EXCLUSION CRITERIA:

  • diastolic blood pressure > 110 mmHg

  • islet call antibodies positive

  • proliferative retinopathy

  • proteinuria

  • myocardial infarction within the last 12 months

  • angina pectoris causing pain daily

  • heart failure

  • malignancy

  • collagenoses

DIAGNOSTIC CRITERIA: WHO

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR/4NR

Control: NR/5/NR

Interventions

NUMBER OF STUDY CENTRES: NR

COUNTRY/LOCATION: Norway

SETTING: outpatients

TREATMENT BEFORE STUDY: NR

TITRATION PERIOD: titrated during trial

GLYCAEMIC TARGET: FBG < 7 mmol/L and a postprandial blood glucose < 10 mmol/L

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): retinopathy, nephropathy, macrovascular disease, metabolic profile

Study details

RUN‐IN PERIOD: at least 3 months

DURATION OF INTERVENTION: 42 months

DURATION OF FOLLOW‐UP: 42 months

STUDY TERMINATED BEFORE REGULAR END: yes. Planned duration of the trial was 5 years, but as almost all participants in the sulphonylurea group ended up on insulin the trial was stopped

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "In our study, our aim was to investigate the long‐term effects of insulin versus SU therapy in type 2 diabetic subjects on glycaemic control, insulin resistance, microalbuminuria and levels of Lp(a) lipoprotein, triglycerides (TG), total‐ and HDL cholesterol, and diastolic and systolic blood pressure."

Notes

Number treated with antihypertensives is the number of participants prescribed ACE‐inhibitors

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: ".., they were randomly assigned to treatment…."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

We assume not blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Loss to follow‐up and their reasons not clearly described

Selective reporting (reporting bias)

High risk

Do not report primary outcome

Academic bias

Low risk

Primary author's first publication on the interventions. Have previously published trials with glibenclamide, but with other comparators (Birkeland 1994)

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Campbell 1994

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glipizide

Control: metformin

Participants

INCLUSION CRITERIA:

  • T2DM

  • 40 to 69 years old

EXCLUSION CRITERIA:

NR

DIAGNOSTIC CRITERIA:
FPG > 8 mmol/L on 2 occasions 2 weeks apart on diet

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: 0/3/NR

Control: 0/4/NR

Interventions

NUMBER OF STUDY CENTRES: NR

COUNTRY/LOCATION: United Kingdom

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: up to 6 weeks

GLYCAEMIC TARGET:

FPG < 8 mmol/L (but more than 4)

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): glycaemic control, body weight, serum lipids, blood lactate and urinary albumin excretion

Study details

RUN‐IN PERIOD: 2 weeks

DURATION OF INTERVENTION: 12 months

DURATION OF FOLLOW‐UP: 12 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING: NR

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "This present study is a long term comparison of metformin and the second generation sulphonylurea, glipizide in diet failed type 2 diabetes subjects, unstratified for weight, assessing glycaemic control, body weight, serum lipids, blood lactate and urinary albumin excretion over a 12 month period."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "…subjects were randomised in blocks of four (11) to receive…"

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Open‐label design

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No participants lost to follow‐up

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Unclear risk

Funding not reported

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Charbonnel 2005

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: gliclazide

Control: pioglitazone

Participants

INCLUSION CRITERIA:

  • T2DM inadequately treated with diet alone

  • HbA1c between 7.5% and 11% with stable or worsening glycaemic control over a period of at least 3 months

  • 35 to 75 years

EXCLUSION CRITERIA:

  • previously use of glucose‐lowering pharmacotherapy at any time

  • any specific contraindications to either drug

  • long‐term treatment with corticosteroids and the start of ß‐blockers were not permitted during the study or within 4 weeks prior to screening

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 209

COUNTRY/LOCATION: Europe, Australia, Canada, South Africa and Israel

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: 16 weeks

GLYCAEMIC TARGET: HbA1c < 8%

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, FPG, insulin, lipids

Study details

RUN‐IN PERIOD: none

DURATION OF INTERVENTION: 52 weeks

DURATION OF FOLLOW‐UP: 52 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "This study compared the effects of pioglitazone and gliclazide on metabolic control in drug‐naïve patients with Type 2 diabetes mellitus."

Notes

This trial is the first 52 weeks of Tan 2005 (Tan 2005)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Patients were randomized in…."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "…, double‐dummy, double‐blind,...."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

We assume they were blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Some of the participants were randomised, but not included in the analysis:

8 participants were not treated; 12 participants had unreliable data. It is not described to which group they originally were randomised to

Selective reporting (reporting bias)

Unclear risk

No protocol or design article available

Academic bias

Low risk

Primary author has not previously conducted trials comparing the same interventions

Sponsor bias

High risk

Received funding from pharmaceutical company

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, adequate blinding
Collier 1989

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: gliclazide

Control: metformin

Participants

INCLUSION CRITERIA:

  • T2DM

  • patients with HbA1c > 9% at the end of the dietary run‐in period were randomised

EXCLUSION CRITERIA: other medication

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: 0/0/0

Control: 0/0/0

Interventions

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: NR

SETTING: outpatients

TREATMENT BEFORE STUDY: no antidiabetic intervention

TITRATION PERIOD: NR

GLYCAEMIC TARGET: not clear, but HbA1c < 8% is specified as the normal range

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): platelet density profiles, intraplatelet nucleotides, intraplatelet nucleotides, intraplatelet β‐thromboglobulin, plasma β triglyceride levels, intraplatelet cyclic AMP levels, platelet release reaction, platelet thromboxane B2 production and plasma fibrinogen levels

Study details

RUN‐IN PERIOD: 3 to 6 weeks

DURATION OF INTERVENTION: 6 months

DURATION OF FOLLOW‐UP: 6 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "In this study we investigated the changes in platelet density profiles, intraplatelet nucleotides, intraplatelet nucleotides, intraplatelet β‐thromboglobulin (β), plasma βTG levels, intraplatelet cyclic AMP (cAMP) levels, platelet release reaction, platelet thromboxane (TX)B2 production and plasma fibrinogen levels in 24 newly diagnosed non‐insulin‐dependent diabetic patients."

Notes

The group of 12 comparable aged controls are not included in the analysis

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "..,and were therefore randomized into either metformin (Glucophage) or gliclazide (Diamicron) treatment groups, .."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Open‐label design, we assume not blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Small study, no drop‐outs reported

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Coniff 1995

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: tolbutamide

Control 1: acarbose

Control 2: placebo

Participants

INCLUSION CRITERIA:

  • T2DM of at least 6 months’ duration

  • 18 years of age

  • stable body weight (+/‐ 5 kg within the previous 3 months)

  • FPG of at least 140 mg/dL

EXCLUSION CRITERIA:

  • significant diseases or conditions likely to alter the course of their diabetes or their ability to complete the study

  • documented gastrointestinal diseases likely to be associated with abnormal gut motility or altered absorption of nutrients

  • known or suspected lactose intolerance

  • severe and poorly controlled diabetes

  • concomitant treatment with sulphonylureas, insulin, hypolipaemic agents, glucocorticoids,

  • other investigational drugs, or medications that might significantly alter gastrointestinal motility or absorption

  • inability to swallow tablets

  • known hypersensitivity to tolbutamide

  • impairment of hepatic and/or renal function resulting in impaired metabolism and/or excretion of tolbutamide

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: 0

Control 1: 0

Control 2: 0

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: 0

Control 1: 0

Control 2: 0

Interventions

NUMBER OF STUDY CENTRES: NR

COUNTRY/LOCATION: USA

SETTING: outpatients

TREATMENT BEFORE STUDY: diet. Patients on sulphonylurea or insulin therapy had these medications discontinued at least 4 weeks prior to enrolment

TITRATION PERIOD: titrated during trial

GLYCAEMIC TARGET: 1 hour postprandial plasma glucose level < 200 mg/dl

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): change in HbA1c, full‐meal test tolerance, adverse events (including hypoglycaemia), blood lipids, change in HbA1c from each scheduled visit

Study details

RUN‐IN PERIOD: 6 weeks

DURATION OF INTERVENTION: 24 weeks

DURATION OF FOLLOW‐UP: 30 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "This multicenter, double‐blind study compared the long‐term efficacy and safety of treatment with placebo, acarbose alone, tolbutamide alone, and acarbose combined with tolbutamide in NIDDM patients treated with a standard diabetic diet."

Notes

The intervention group combining tolbutamide with acarbose is not included in the analyses

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "…, patients were stratified based on fasting glucose level (stratum I ≤1200 mg/dL versus stratum II > 200 mg/dL) and randomized to receive 24 weeks of treatment with acarbose, tolbutamide, acarbose‐plus‐tolbutamide, or placebo."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote: "...was followed by a double‐blind treatment for 24 weeks..."

Method of blinding not described

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NR

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss to follow‐up adequately described

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Unclear sequence generation, allocation concealment and blinding
Dalzell 1986

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: blinding not described, but we assume open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: tolbutamide

Comparator: metformin

Participants

INCLUSION CRITERIA:

  • T2DM

  • normal or overweight

  • FPG persistently above 11 mmol/L

  • managed with diet for at least 6 months

EXCLUSION CRITERIA: NR

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Comparator: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Comparator: NR

Interventions

NUMBER OF STUDY CENTRES: NR

COUNTRY/LOCATION: Ireland

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: NR

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): plasma glucose, fasting lipids and dietary adherence

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 1 year

DURATION OF FOLLOW‐UP: 1 year

STUDY TERMINATED BEFORE REGULAR END: NR

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING: NR

PUBLICATION STATUS: abstract in peer‐reviewed journal

Stated aim of study

Quote: "This study compares the effect of tolbutamide and metformin on plasma glucose and fasting lipids in the management of NIDDM with persistent severe hypoglycaemia despite good dietary adherence."

Notes

It was not possible to find any address of a corresponding author

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "…, were randomized to treatment with…."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

NR

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NR

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

NR

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Unclear risk

Funding not reported

Trials according to risk of bias

Unclear risk

Unclear sequence generation, allocation concealment and blinding
DeFronzo 1995

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: metformin

Participants

INCLUSION CRITERIA:

  • lack acceptable glycaemic control (FPG ≥ 140 mg per decilitre) after at least 4 weeks of dietary therapy plus 20 mg of glyburide per day

  • weight of 120 to 170 per cent of ideal (on the basis of 1983 Metropolitan Life Insurance tables)

  • age of 40 to 70 years

  • normal renal function (serum creatinine ≤ 1.4 mg per decilitre (124 μmol per litre) in men and ≤ 1.3 mg per decilitre (115 μmol per litre) in women; and ≤ 2+ proteinuria)

  • normal liver function

EXCLUSION CRITERIA:

  • symptomatic diabetes (polyuria, polydipsia and weight loss)

  • symptomatic cardiovascular disease

  • diastolic blood pressure above 100 mm Hg during antihypertensive drug treatment

  • any concurrent medical illness

  • received insulin therapy within the previous 6 months

  • used medications known to affect glucose metabolism

  • drank 3 or more alcoholic drinks per day (≥ 3 oz of alcohol per day)

  • used illicit drugs

  • previously received metformin therapy

DIAGNOSTIC CRITERIA:

The diagnosis of T2DM was based on clinical history and the finding of a fasting plasma glucose concentration above 140 mg per decilitre (7.8 mmol per litre) on 2 occasions

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: NR, but multicentre

COUNTRY/LOCATION: USA

SETTING: outpatients

TREATMENT BEFORE STUDY: NR

TITRATION PERIOD: 5 weeks

GLYCAEMIC TARGET: FPG < 140 mg per decilitre

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): ‐

Study details

RUN‐IN PERIOD: 5 weeks

DURATION OF INTERVENTION: 29 weeks

DURATION OF FOLLOW‐UP: 29 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "This report describes the results of two randomized, placebo‐controlled, multicenter trials in which moderately obese patients with NIDDM whose diabetes was poorly controlled with diet alone or with diet plus a sulfonylurea drug were treated with metformin for 29 weeks."

Notes

The intervention group with glibenclamide plus metformin combination therapy is not included

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "....patients were randomly assigned to treatment with........"

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

The trial is described as double‐blind, but the method of blinding not described

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NR

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Reasons for withdrawals are not sufficient

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Unclear sequence generation, allocation concealment and blinding
Deng 2003

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: xiaoyoasan jiajian

Participants

INCLUSION CRITERIA: T2DM

EXCLUSION CRITERIA: NR

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: China

SETTING: NR

TREATMENT BEFORE STUDY: NR

TITRATION PERIOD: NR

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): FBG, 2‐hour post‐prandial blood glucose and HbA1c

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 6 months

DURATION OF FOLLOW‐UP: 6 months

STUDY TERMINATED BEFORE REGULAR END: NR

Publication details

LANGUAGE OF PUBLICATION: Chinese

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

According to Chinese extractor, NR

Notes

Extracted by a Chinese collaborator

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Is a randomised clinical trial. Generation of sequence generation not described.

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Double‐blind, but method not described

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NR

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

NR

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Unclear risk

Funding not reported

Trials according to risk of bias

Unclear risk

Unclear sequence generation, allocation concealment and blinding
Derosa 2003

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glimepiride

Control: repaglinide

Participants

INCLUSION CRITERIA:

  • T2DM ≥ 6 months

  • nonsmokers with normal blood pressure (WHO criteria: systolic blood pressure < 130 mmHg and diastolic blood pressure < 85 mmHg, no coronary heart disease and normal renal function (serum creatinine < 1.5 mg/dl))

  • receiving no antidiabetic medications at the time of enrolment and had not achieved satisfactory glycaemic control (HbA1c > 7.0%) with diet and exercise alone

  • low‐density lipoprotein concentrations > 100 mg/dl

  • no hypolipidaemic drugs, diuretics, beta‐blockers or thyroxin

EXCLUSION CRITERIA: NR

DIAGNOSTIC CRITERIA: ADA criteria

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR/0/0

Control: NR/0/0

Interventions

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: Italy

SETTING: outpatients

TREATMENT BEFORE STUDY: treatment‐naive

TITRATION PERIOD: 8 weeks

GLYCAEMIC TARGET: FPG < 120 mg/dl; postprandial plasma glucose < 160 mg/dl 2 hours after meal; HbA1c < 7%

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): glycaemic control, lipoprotein (a), plasminogen activator inhibitor‐1, homocysteine, biochemical variables, blood pressure

Study details

RUN‐IN PERIOD: 4 weeks

DURATION OF INTERVENTION: 14 months

DURATION OF FOLLOW‐UP: 14 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "The present study was designed to compare the effects of repaglinide and glimepiride on measures of glycemic control in patients with type 2 diabetes and to determine whether these agents have differing effects on levels of Lp(a), PAl‐l, and Hcy"

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Randomization codes were prepared by a statistician and placed in envelopes; the statistician subsequently carried out randomization by drawing the envelopes."

Allocation concealment (selection bias)

Low risk

Quote: "Randomization codes were prepared by a statistician and placed in envelopes; the statistician subsequently carried out randomization by drawing the envelopes."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "..., blinding of the investigators and patients was maintained through the use of identical numbered bottles prepared by the hospital pharmacy."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

We assume blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Sufficient description of patients lost to follow‐up

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Not published trials investigating the same interventions (in monotherapy) previously

Sponsor bias

Unclear risk

Funding not reported

Trials according to risk of bias

Unclear risk

Unclear sequence generation, adequate allocation concealment and blinding
Derosa 2004

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glimepiride

Control: metformin

Participants

INCLUSION CRITERIA:

  • T2DM ≥ 6 months

  • nonsmokers with normal blood pressure (WHO criteria: systolic blood pressure < 130 mmHg and diastolic blood pressure < 85 mmHg, no coronary heart disease and normal renal function (serum creatinine < 1.5 mg/dl)

  • no hypolipidaemic drugs, diuretics, beta‐blockers or thyroxin

EXCLUSION CRITERIA:

  • abnormal liver or kidney function

  • history of chronic insulin treatment

  • active cardiac problems

  • known contradictions to sulphonylurea or biguanides

  • pregnancy

  • breastfeeding

  • intending to get pregnant

  • systemic treatment with corticosteroids

DIAGNOSTIC CRITERIA: ADA criteria

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR/0/0

Control: NR/0/0

Interventions

NUMBER OF STUDY CENTRES: 3

COUNTRY/LOCATION: Italy

SETTING: outpatients

TREATMENT BEFORE STUDY: NR

TITRATION PERIOD: 8 weeks

GLYCAEMIC TARGET: FPG < 120 mg/dl; postprandial plasma glucose < 160 mg/dl 2 hours after meal

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): extra glycaemic parameters, specifically those associated with cardiovascular risk. Glycaemic efficacy

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 12 months (+ 8 weeks titration period)

DURATION OF FOLLOW‐UP: 12 months (+ 8 weeks titration period)

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "The aim of the study was to compare the metabolic effects of glimepiride and metformin in patients with T2DM."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "...,randomised,.."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Open‐label design

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Sufficient description of patients lost to follow‐up

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Not published trials investigating the same interventions (in monotherapy) previously

Sponsor bias

Unclear risk

Funding not reported

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment. Inadequate blinding
Diehl 1985

Methods

CROSS‐OVER RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: not described, we assume open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: chlorpropamide

Control: insulin

Participants

INCLUSION CRITERIA:

  • fasting serum glucose of 150 mg/dl or higher on 2 occasions

  • newly diagnosed or no hypoglycaemic medication the previous 12 months

  • > 30 years

EXCLUSION CRITERIA:

  • history of ketoacidosis

  • serum creatinine > 1.5 mg/dl

  • pregnancy

  • taking more than 2 other medications daily

  • poor visual acuity

  • handicaps preventing using a syringe

  • major co‐morbidities

DIAGNOSTIC CRITERIA: fasting serum glucose of 150 mg/dl or higher on 2 occasions

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: USA

SETTING: outpatients

TREATMENT BEFORE STUDY: diet or antidiabetic interventions the previously 12 months

TITRATION PERIOD: NR

GLYCAEMIC TARGET: achieve fasting glucose levels of ≤ 140 mg/dl while avoiding hypoglycaemic symptoms

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): compliance

Study details

RUN‐IN PERIOD: 4 weeks

DURATION OF INTERVENTION: 24 weeks

DURATION OF FOLLOW‐UP: 24 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "We compared compliance with insulin and chlorpropamide in patients newly beginning medication for NIDDM."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "…were randomly assigned using opaque sealed envelopes to therapy…"

Through correspondence, the primary author informed us that randomisation was done with a table of random number

Allocation concealment (selection bias)

Low risk

Quote: "…were randomly assigned using opaque sealed envelopes to therapy…"

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Through correspondence we were told that the outcome assessors were blinded for the primary outcome

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Drop‐outs and reasons described, but not possible to judge whether from first or second treatment period

Selective reporting (reporting bias)

Low risk

No trial protocol or design article available, but the primary authors confirmed the predefined outcomes through correspondence

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Adequate sequence generation and allocation concealment, inadequate blinding of participants, adequate blinding of outcome assessors

Ebeling 2001

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control 1: pioglitazone

Control 2: placebo

Participants

INCLUSION CRITERIA:

  • T2DM treated with diet and 1 oral medication or diet alone

  • BMI ≥ 25 kg/m2

  • 35 years or older and 75 years or younger

  • HbA1c ≥ 7.5%

  • fasting serum glucose ≥ 7.8 mmol/L

EXCLUSION CRITERIA: NR

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control 1: NR

Control 2: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control 1: NR

Control 2: NR

Interventions

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: Finland

SETTING: outpatients

TREATMENT BEFORE STUDY: diet with or without one oral agent

TITRATION PERIOD: titrated during trial

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): glycaemic control, acute phase proteins and the influence of complement activation

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 6 months

DURATION OF FOLLOW‐UP: 6 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "We wanted to study how these proteins are related to complement activation in type 2 diabetes and how improvement of glycemic control affects them or complement activation."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "We wanted to study how these proteins are related to complement activation in type 2 diabetes and how improvement of glycemic control affects them or complement activation."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote: "This study was performed in a randomized double‐blind manner."

Method of blinding not described

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NR

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Loss to follow‐up not described

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Unclear sequence generation, allocation concealment and blinding
Esposito 2004

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: repaglinide

Participants

INCLUSION CRITERIA:

  • diagnosis of T2DM for < 3 years

  • 35 to 70 years of age

  • BMI ≥ 24 kg/m2

  • HbA1c ≥ 6.5%

  • treated with diet or oral drugs

EXCLUSION CRITERIA:

  • need for insulin use

  • concomitant chronic diseases, including kidney, liver and cardiovascular diseases; recent acute illness or change in diet, treatment or lifestyle within the 3 months before the study

  • severe uncontrolled hypertension (blood pressure < 200/100 mmHg)

  • pregnant women or women who intended to become pregnant

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: Italy

SETTING: outpatients

TREATMENT BEFORE STUDY: treatment‐naive or peroral antidiabetic drugs

TITRATION PERIOD: 6 to 8 weeks

GLYCAEMIC TARGET:

  • FBG < 110 mg/dL

  • postprandial glucose < 140 mg/dL

  • HbA1c < 6.5%

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): carotis intima media thickness, biochemical variables, markers of systemic vascular inflammation

Study details

RUN‐IN PERIOD: none

DURATION OF INTERVENTION: 12 months plus 6 to 8 weeks (titration period)

DURATION OF FOLLOW‐UP: 12 months plus 6 to 8 weeks (titration period)

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "We compared the effects of two insulin secretagogues, repaglinide and glyburide, known to have different efficacy on postprandial hyperglycemia, on carotid intima‐media thickness (CIMT) and markers of systemic vascular inflammation in type 2 diabetic patients."

Notes

Non‐diabetic control group not included in the analysis

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "A total of 175 diabetic patients were randomly assigned to open‐label treatment with either repaglinide or glyburide, through the use of a computer‐generated random number sequence (Figure 1)."

Allocation concealment (selection bias)

Low risk

Quote: "Allocation was concealed in sealed study folders that were held in a central, secured location until after informed consent was obtained."

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "The laboratory staff did not know the participants’ group assignments."

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Not clearly described reason for drop‐outs in each intervention group

Selective reporting (reporting bias)

Low risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Low risk

No commercial funding

Trials according to risk of bias

Unclear risk

Adequate sequence generation and allocation concealment, inadequate blinding of participants and investigators, adequate blinding of outcome assessors

Feinböck 2003

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glimepiride

Control: acarbose

Participants

INCLUSION CRITERIA:

  • T2DM not adequately controlled on diet alone

  • 36 to 80 years

  • HbA1c ≥ 7.8%

  • BMI between 24 and 35 kg/m2

EXCLUSION CRITERIA:

  • previous antidiabetic drugs for more than 4 weeks during the last 3 months

  • serious late diabetic complications

  • serum glutamic oxalacetic transferase or serum glutamic pyruvic transaminase greater than 2 times the upper limit

  • creatinine levels > 132.6 µmol/L

  • pregnant or not using a reliable method of birth control during the study period

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 17

COUNTRY/LOCATION: Austria

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: 6 weeks

GLYCAEMIC TARGET: FBG 7.8 mmol/L

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): number of responders in each intervention group, change in HbA1c, weight, postprandial blood glucose and C‐peptide levels from baseline, standard biochemical variables and C‐peptide

Study details

RUN‐IN PERIOD: none

DURATION OF INTERVENTION: 26 weeks

DURATION OF FOLLOW‐UP: 26 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "In the present study the efficacy, compliance and safety of acarbose and glimepiride were compared in patients with T2DM over a period of 26 weeks in a multicentre trial in Austria."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Eligible patients were randomized (stratified by study center, blocked) to a dose‐finding phase…"

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Only describe that blood samples were analysed in a central laboratory

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss to follow‐up adequately described

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Fineberg 1980

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glipizide

Control: tolbutamide

Participants

INCLUSION CRITERIA:

  • above 30 years (female adults using contraceptives or unable to bear children)

  • life expectancy at least 5 years

  • diabetes as confirmed by an oral glucose tolerance test on admission

  • ability to adhere to diet and medication regimens

EXCLUSION CRITERIA:

  • juvenile‐onset or unstable diabetes mellitus

  • hepatic or renal insufficiency

  • use of diabetogenic drugs

  • history of drug abuse or non‐compliant behaviour

  • previous sulphonylurea therapy failure

DIAGNOSTIC CRITERIA: United States Public Health Service criteria

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: NR

COUNTRY/LOCATION: USA

SETTING: outpatients

TREATMENT BEFORE STUDY: diet and/or antidiabetic drugs

TITRATION PERIOD: individual. Until max dose or satisfactory glycaemic control

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): fasting and 2‐hour postprandial serum glucose levels, insulin secretion and dynamics and glucose disappearance rates

Study details

RUN‐IN PERIOD: 4 weeks

DURATION OF INTERVENTION: 6 months

DURATION OF FOLLOW‐UP: 6 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "Insulin secretion and dynamics and glucose disappearance rates (Kg) were studied before and at the end of the sixth month of therapy"

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Patients then entered the active drug titration phase and were assigned consecutive numbers which were matched with a corresponding list of computer generated random drug assignments."

Allocation concealment (selection bias)

Low risk

Quote: "Patients then entered the active drug titration phase and were assigned consecutive numbers which were matched with a corresponding list of computer generated random drug assignments."

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Open‐label design

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Not reported to which group the patients lost to follow‐up belonged

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from a pharmaceutical industry

Trials according to risk of bias

Unclear risk

Adequate sequence generation and allocation concealment, inadequate blinding
Foley 2009

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: gliclazide

Control: vildagliptin

Participants

INCLUSION CRITERIA:

  • T2DM

  • HbA1c 7.5% to 11% while receiving no pharmacologic treatment (patients who had taken no oral antidiabetic drug for at least 12 weeks prior to screening and no oral antidiabetic drug for > 3 consecutive months at any time in the past were considered to be representative of a drug naive population)

  • ≥ 18 years

  • with a BMI in the range of 22 to 45 kg/m2

  • FPG < 15 mmol/L

EXCLUSION CRITERIA:

  • pregnant or lactating

  • history of type 1 diabetes

  • pancreatic injury

  • secondary forms of diabetes

  • symptomatic autonomic neuropathy

  • acute infections

  • congestive heart failure NYHA class III or IV

  • electrocardiogram abnormalities

  • cirrhosis

  • chronic active hepatitis

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 151

COUNTRY/LOCATION: 16 countries (Europe, Latin America and South Africa)

SETTING: outpatients

TREATMENT BEFORE STUDY: treatment‐naive

TITRATION PERIOD: 12 weeks

GLYCAEMIC TARGET: FPG was < 7 mmol/L

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): change in HbA1c from baseline, body weight, FPG, fasting plasma lipids, fasting proinsulin, fasting insulin, fasting proinsulin/insulin ratio and homeostasis model assessment of insulin resistance (HOMA IR), adverse events both by regular physical examination and measurement of blood chemistry, haematology and urinalysis

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 104 weeks

DURATION OF FOLLOW‐UP: 104 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "...designed to compare the efficacy and safety of two years of monotherapy with vildagliptin 50 mg bid and gliclazide up to 320 mg/day in drug‐naïve patients with type 2 diabetes."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote:"..,multi‐center, double‐blind, randomized, active‐controlled study to compare…"

Allocation concealment (selection bias)

Unclear risk

Quote:"..,multi‐center, double‐blind, randomized, active‐controlled study to compare…"

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote:"..,multi‐center, double‐blind, randomized, active‐controlled study to compare…"

Method of blinding not described

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

See above

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Reason for loss to follow‐up described

Selective reporting (reporting bias)

Low risk

All outcomes from clinicaltrials.gov reported

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received grant from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Unclear sequence generation, allocation concealment and blinding
Forst 2003

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Comparator: insulin lispro

Participants

INCLUSION CRITERIA:

  • T2DM

  • 35 to 70 years

  • HbA1c < 1.7 fold normal‐upper limit

  • C‐peptide response ≥ 0.4 nmol/L after intravenous injection of 1.0 mg glucagon

EXCLUSION CRITERIA: insulin therapy

DIAGNOSTIC CRITERIA: WHO

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Comparator: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVE/LIPID‐LOWERING:

Sulphonylurea: NR

Comparator: NR

Interventions

NUMBER OF STUDY CENTRES: 19

COUNTRY/LOCATION: Sweden, Germany and Switzerland

SETTING: outpatients

TREATMENT BEFORE STUDY: drug naive or oral antidiabetic

TITRATION PERIOD: NR

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): postprandial blood glucose excursion, glycaemic control, biochemical variables, safety data

Study details

RUN‐IN PERIOD: 6 weeks

DURATION OF INTERVENTION: 24 weeks

DURATION OF FOLLOW‐UP: 24 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "In the present study the efficacy and safety of the preprandial injections of insulin lispro were compared with the oral administration of glibenclamide in patients with type 2 diabetes"

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Seventy‐five patients were randomized to…"

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

We assume not blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All completed the trial

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Forst 2005

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glimepiride

Comparator: pioglitazone

Participants

INCLUSION CRITERIA:

  • T2DM

  • 40 to 75 years of age

  • HbA1c between 6.6% and 9.9%

EXCLUSION CRITERIA:

  • type 1 diabetes

  • smoking

  • clinically significant cardiovascular, renal or hepatic disease

DIAGNOSTIC CRITERIA: ADA criteria

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: glimepiride

Comparator: pioglitazone

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: 26/41/13

Comparator: 25/52/18

Interventions

NUMBER OF STUDY CENTRES: 1, we assume

COUNTRY/LOCATION: Germany

SETTING: outpatients

TREATMENT BEFORE STUDY: not specified

TITRATION PERIOD: not described

GLYCAEMIC TARGET: morning blood glucose levels less than 6.7 mmol/L

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): heat‐stimulated microvascular blood flow, biochemical variables

Study details

RUN‐IN PERIOD: not described

DURATION OF INTERVENTION: 24 weeks

DURATION OF FOLLOW‐UP: 24 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING: no

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "The present study was performed to investigate the effect of improving glucose control and insulin sensitivity by activating PPAR‐γ with pioglitazone, in comparison with glimepiride treatment, on metabolic control, insulin resistance, and microvascular function in patients with type 2 diabetes."

Notes

It is not clearly described whether the trial is open‐label or not, but we assume it to be open‐label, because the addition of other antidiabetic drugs, if intervention failure differed between the 2 interventions

The number reported for patients with antihypertensive is the number of patients receiving angiotensin 2‐antagonist or ACE‐inhibitor. Number of lipid‐lowering is the number of patients on statins

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "After randomization, patients..."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Probably open‐label

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NR

Incomplete outcome data (attrition bias)
All outcomes

High risk

179 patients randomised, but only 173 reported. Unknown why the 6 patients did not complete the trial

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Unclear sequence generation, allocation concealment and blinding
Hanefeld 2011

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control 1: rosiglitazone 4 mg

Control 2: rosiglitazone 8 mg

Participants

INCLUSION CRITERIA:

  • T2DM with a C‐peptide level ≥ 0.8 ng/ml and a fasting plasma glucose ≥ 126 mg/dl (7.0 mmol/L) and ≤ 270 mg/dl (15.0 mmol/L) at 4 and 2 weeks before randomisation

  • men and women aged 40 to 80 years

EXCLUSION CRITERIA:

Patients who had diabetic complications requiring treatment, serious renal, hepatic or haematological impairment, women of childbearing potential and insulin use were excluded

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control 1: NR

Control 2: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control 1: NR

Control 2: NR

Interventions

NUMBER OF STUDY CENTRES: 71

COUNTRY/LOCATION: France, Germany, Italy, UK, Belgium, Sweden, Ireland and Netherlands

SETTING: outpatients

TREATMENT BEFORE STUDY: diet or oral therapy (withdrawn 6 months before randomisation)

TITRATION PERIOD: 12 weeks

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, FPG, fructosamine, C‐peptide, insulin, pro‐insulin, 32‐33 split pro‐insulin, urinary albumin, albumin excretion rate and serum lipids

Study details

RUN‐IN PERIOD: 4 to 6 weeks

DURATION OF INTERVENTION: 52 weeks

DURATION OF FOLLOW‐UP: 52 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: one of the publications is an article in a peer‐reviewed journal, the other is from the GlaxoSmithKline website

Stated aim of study

Quote: "Sulphonylureas (SU) act by increasing endogenous insulin secretion. Rosiglitazone (RSG) acts predominantly by increasing insulin sensitivity and this study was to determine if RSG was a viable alternative to glibenclamide in first‐line therapy in patients with type 2 diabetes."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "....patients who were randomised...."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "Rosiglitazone, glibenclamide and placebo capsules were matched for weight, shape and colour. A double‐dummy system allowed ‘‘titration’’ of rosiglitazone without a change of dose."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

We assume due to double‐blind design

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Loss to follow‐up sufficiently described

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Sponsored by pharmaceutical company

Trials according to risk of bias

Unclear risk

Unclear sequence generation, allocation concealment, adequate blinding
Harrower 1985

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: second‐generation sulphonylurea: glipizide, gliquidone, gliclazide and glibenclamide

Control: chlorpropamide

Participants

INCLUSION CRITERIA:

  • T2DM

  • failed to be controlled on diet

EXCLUSION CRITERIA: NR

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: NR

COUNTRY/LOCATION: Scotland

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: NR

GLYCAEMIC TARGET: NR, describe normal range from 5.6% to 8.7%

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): diabetic control, biochemical variables

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 12 months

DURATION OF FOLLOW‐UP: 12 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

NON‐COMMERCIAL FUNDING: not directly, but was sponsored by the medical unit of a general hospital in Scotland

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "Five currently available sulphonylureas were compared to see whether, in routine use for 1 year, they produced any major differences in diabetic control."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "The patients were randomly allocated to one of five concurrent treatment groups…"

Correspondence with author: the patients were randomly allocated using a card system with the drugs named on each card and placed randomly in a box

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

The outcome assessors were blinded. Information through correspondence

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss to follow‐up sufficiently described

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Low risk

No funding from pharmaceutical industry. Information through correspondence

Trials according to risk of bias

Unclear risk

Unclear sequence generation, allocation concealment and blinding
Hermann 1991

Methods

CROSS‐OVER RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: metformin

Participants

INCLUSION CRITERIA:

  • T2DM

  • younger than 70 years

  • normal serum creatinine and transaminase

  • modest control on current therapy of glibenclamide (FPG < 9 mmol/L and HbA1c < 11%)

EXCLUSION CRITERIA:

Persistent high blood glucose level on maximally tolerated dose of glibenclamide (FBG > 12 mmol/L) and/or intolerable adverse effects

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 2

COUNTRY/LOCATION: Sweden

SETTING: outpatients

TREATMENT BEFORE STUDY: diet and/or glibenclamide

TITRATION PERIOD: NR

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): glycaemic control, lipids, C‐peptide

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 6 months

DURATION OF FOLLOW‐UP: 6 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "The purpose of the present study was to compare long‐term metformin and glibenclamide treatment in their effects on glycaemic control, weight, lipids, lipoproteins and insulin secretion."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

The participants were randomised to the 2 interventions by help of a table of random numbers (correspondence with author)

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

We assume not blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

3 participants lost to follow‐up. Not clearly reported in which group they belonged

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Adequate sequence generation, unclear allocation concealment, inadequate blinding
Hermann 1991a

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: metformin

Participants

INCLUSION CRITERIA:

  • FBG ≥ 6.7 mmol/L on at least 2 occasions and/or abnormal glucose tolerance according to WHO

  • if FBG ≥ 6.7 mmol/L after 2 months of diet alone, patients were randomised

EXCLUSION CRITERIA:

  • ketonuria

  • pregnancy

  • impaired renal function (serum creatinine above normal)

  • impaired hepatic function (elevated liver enzymes and/or other liver function tests), i.e. liver disease of a certain severity

  • known alcoholism

  • significant cardiac insufficiency

  • severe hypertension

  • severe retinopathy

  • serious chronic disease (cancer etc.)

  • periodic intake of drugs influencing glucose tolerance. If the patient received chronic drug therapy it must be kept constant during the study

  • drugs that interact with sulphonylurea

DIAGNOSTIC CRITERIA: WHO

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

12% of all participants had coronary heart disease

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

40% of all participants received beta‐blockers

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 5

COUNTRY/LOCATION: Sweden

SETTING: outpatients

TREATMENT BEFORE STUDY: diet or oral antidiabetic agents (had to be withdrawn 2 to 3 weeks before study entry)

TITRATION PERIOD: 2 to 12 weeks

GLYCAEMIC TARGET: FBG < 6.7 mmol/L

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): efficacy and safety, responders, additive effect of sulphonylurea and metformin, lipids, insulin

Study details

RUN‐IN PERIOD: 8 weeks (6 weeks on diet followed by 2 weeks with placebo tablets)

DURATION OF INTERVENTION: 6 months + 2 to 12 weeks

DURATION OF FOLLOW‐UP: 6 months + 2 to 12 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "To assess and compare the therapeutic efficacy and safety of metformin (M) and sulfonylurea (glyburide, G), alone and in various combinations, in patients with non‐insulin‐dependent diabetes mellitus (NIDDM)."

Notes

The group of participants randomised to receive metformin and glibenclamide combination therapy from the start is not included in the meta‐analysis

After diet period the patients underwent a main randomisation, early randomisation or delayed randomisation according to the FBG

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: ".., patients were randomized (Fig. 1) according to computer‐generated lists…"

Allocation concealment (selection bias)

Low risk

Quote: ".., patients were randomized (Fig. 1) according to computer‐generated lists…"

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "To obtain truly double‐blind conditions, the study used a double dummy technique."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

We assume due to double‐blind design

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss to follow‐up sufficiently described

Selective reporting (reporting bias)

Low risk

All predefined primary and secondary outcomes are clearly described in trial protocol and assessed

Academic bias

High risk

Published Hermann 1991 previous to this trial

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Low risk

Adequate sequence generation, allocation concealment and blinding
Hoffmann 1990

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Comparator: acarbose

Participants

INCLUSION CRITERIA:

  • T2DM

  • 50 to 70 years

  • not satisfactorily regulated on diet

  • 2 fasting blood glucose values of at least 140 mg/100 ml

  • HbA1c at least 8.8%

EXCLUSION CRITERIA:

  • Broca index larger than 1.1

  • pharmacological diabetes therapy for the last 8 weeks

  • need for insulin therapy

  • pregnancy and lactation

  • decompensated heart insuffiencey

  • liver and kidney disease

  • malignant tumours

  • enteropathy

  • angiopathy

  • fever infection

  • laxative or obstipation medicaments

  • taking part in another randomised trial

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Comparator: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Comparator: NR

Interventions

NUMBER OF STUDY CENTRES: 5

COUNTRY/LOCATION: Germany

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: 4 weeks

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, fasting blood glucose, postprandial blood glucose, renal glucose excretion, subjective compatibility

Study details

RUN‐IN PERIOD: NR, probably none

DURATION OF INTERVENTION: 24 weeks

DURATION OF FOLLOW‐UP: 24 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: German

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING: NR

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "Comparison of acarbose and glibenclamide on efficacy and adverse effects in patients with type II diabetes" [from English abstract]

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Open, randomized study in over 24 weeks in five private practices." [from English abstract]

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label

Blinding of outcome assessment (detection bias)
All outcomes

High risk

We assume not blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Not clearly described

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Unclear risk

Funding not reported

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Hoffmann 1994

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind regarding acarbose/placebo and single‐blinded regarding glibenclamide

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control 1: placebo

Control 2: acarbose

Participants

INCLUSION CRITERIA:

  • T2DM pretreated with diet alone

  • HbA1c 7% to 9%

  • 35 to 70 years

  • duration of diabetes ≥ 3 months

  • stable body weight

  • BMI ≤ 35 kg/m2

EXCLUSION CRITERIA:

  • aspartate‐aminotransferase ≥ 50 U/L

  • alanine‐aminotransferase ≥ 50 U/L

  • creatinine ≥ 2 mg/dl

  • severe disturbances of the haematopoietic system

  • malignant tumours

  • enteropathies

  • febrile infections

  • pregnancy

  • excessive abuse of alcohol or nicotine

  • laxative and constipating drugs

  • lack of willingness to co‐operate

  • simultaneous intake of other test substances

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control 1: NR

Control 2: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control 1: NR

Control 2: NR

Interventions

NUMBER OF STUDY CENTRES: 4

COUNTRY/LOCATION: Germany

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: the drugs were titrated during the trial

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): postprandial insulin increase, HbA1c, blood glucose, insulin and urinary glucose

Study details

RUN‐IN PERIOD: none

DURATION OF INTERVENTION: 24 weeks

DURATION OF FOLLOW‐UP: 24 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "To compare the different therapeutic principles of a α‐glucosidase inhibitors and sulphonylureas as first line treatment in non‐insulin‐dependent diabetes mellitus (NIDDM) patients with primary dietary failure."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "The random list was generated by electronic data processing for 16 balanced blocks of six patients."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Quote: "…double‐blind with respect to acarbose/placebo treatment and single‐blind with respect to the glibenclamide treatment."

The glibenclamide intervention was made single‐blind so the investigators could adjust it to metabolic necessities and to avoid hypoglycaemia

Blinding of outcome assessment (detection bias)
All outcomes

High risk

NR

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All loss to follow‐up reported

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

High risk

Published similar trials previously (Hoffmann 1990)

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Adequate sequence generation, unclear allocation concealment, inadequate blinding
Hollander 1992

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: insulin

Participants

INCLUSION CRITERIA: not specified, but all had T2DM

EXCLUSION CRITERIA: NR

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Comparator: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Comparator: NR

Interventions

NUMBER OF STUDY CENTRES: NR

COUNTRY/LOCATION: NR

SETTING: NR

TREATMENT BEFORE STUDY: NR

TITRATION PERIOD: NR

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, FBG, stimulated C‐peptide

Study details

RUN‐IN PERIOD: 8 weeks

DURATION OF INTERVENTION: 44 weeks

DURATION OF FOLLOW‐UP: 44 weeks

STUDY TERMINATED BEFORE REGULAR END: NR

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING: NR

PUBLICATION STATUS: published as abstract from conference proceeding

Stated aim of study

Not clearly stated, but the title says, Quote: "A randomized clinical trial of glyburide versus insulin using staged diabetes management to achieve euglycemia in NIDDM"

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "A randomized clinical trial of..."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label

Blinding of outcome assessment (detection bias)
All outcomes

High risk

We assume not blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

NR

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Unclear risk

Funding not reported

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Jain 2006

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: pioglitazone

Participants

INCLUSION CRITERIA:

  • recently diagnosed with T2DM (< 2 years)

  • treatment‐naive men and non‐pregnant, non‐lactating women

  • 18 to 80 years of age

  • from USA or Puerto Rico

  • HbA1c between 7.5% and 11.5%

  • fasting C‐peptide level of 1.0 ng/ml or greater

  • fasting glucose level above 120 mg/dl

EXCLUSION CRITERIA:

  • previously treatment with rosiglitazone, pioglitazone or troglitazone within the last 3 months

  • previous alcohol or drug abuse

  • previous treatment with meglitinide analogue, alfa‐glucosidase inhibitor, metformin, insulin or sulphonylurea treatment for 3 months or more

  • use of hydrochlorothiazide greater than 25 mg/day, glucocorticoids, steroid joint injections, niacin greater then 250 mg/day or antidiabetic agents other than the study drugs during the trial

  • concurrent participation or enrolment in another investigational study

  • serum creatinine level above 1.5 mg/dl for men and above 1.4 mg/dl for women

  • greater than 1+ dipstick proteinuria or equivalent

  • anaemia

  • hypertension

  • BMI < 20 or > 45 kg/m2

  • elevated liver enzymes

  • elevated triglycerides

  • NYHA 3 to 4

  • chronic condition expected to require glucocorticoids use

  • acute cardiovascular event within 6 months before screening

  • acute or unstable chronic pulmonary disease or lesions at chest radiography

  • cancer not in remission for the last 5 years

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 65

COUNTRY/LOCATION: USA and Puerto Rico

SETTING: outpatients

TREATMENT BEFORE STUDY: diet and exercise. Other antidiabetics than the one mentioned in the exclusion criteria

TITRATION PERIOD: 16 weeks

GLYCAEMIC TARGET: FPG between 69 and 141 mg/dl

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, adverse events and biochemical variables

Study details

RUN‐IN PERIOD: none

DURATION OF INTERVENTION: 56 weeks

DURATION OF FOLLOW‐UP: 56 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "To evaluate the long‐term safety and efficacy of glyburide versus pioglitazone in patients with a recent diagnosis of type 2 diabetes mellitus."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "…, patients were enrolled and randomly assigned 1:1 by means of…"

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote: "....multicenter, double‐blind trial...."

Method of blinding not described

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NR

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All loss to follow‐up reported

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Unclear sequence generation, allocation concealment and blinding
Jibran 2006

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: blinding not described, but we assume open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: repaglinide

Participants

INCLUSION CRITERIA:

  • newly diagnosed T2DM who remained uncontrolled on diet and exercise

  • 30 to 70 years

EXCLUSION CRITERIA:

  • patients with type 1 diabetes

  • T2DM already taking maximum or near maximum doses of sulphonylurea and whose diabetes was still not controlled (patients with secondary failure)

  • T2DM already on insulin

  • patients taking diabetogenic drugs

  • significant gastrointestinal, cardiovascular or renal disease by history, physical examination or laboratory evidence or having concurrent medical illness

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: 0

Control: 0

Interventions

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: Pakistan

SETTING: outpatients

TREATMENT BEFORE STUDY: diet and exercise

TITRATION PERIOD: titrated during trial

GLYCAEMIC TARGET: FBG < 130 mg/dl and postprandial blood glucose < 175 mg/dl

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): fasting blood glucose , 2 hour postprandial glucose, HbA1c, weight, adverse events, biochemical variables

Study details

RUN‐IN PERIOD: none

DURATION OF INTERVENTION: 12 months

DURATION OF FOLLOW‐UP: 12 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING: NR

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "To evaluate the safety and efficacy (glycaemic control) provided by repaglinide compared with glibenclamide in newly diagnosed type 2 (non‐insulin dependant) diabetic patients."

Notes

Patients taking medication against cardiovascular disease are set to zero as none of the patients were taking long‐term medication

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Fifty patients were randomly selected for each group."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Blinding not described, but we assume open‐label

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Not described, but we assume not blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Loss to follow‐up not described

Selective reporting (reporting bias)

Unclear risk

No design article or study protocol available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Unclear risk

Funding not reported

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Johnston 1997

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control 1: placebo

Control 2: miglitol 25 mg

Control 3: miglitol 50 mg

Participants

INCLUSION CRITERIA:

  • T2DM

  • 60 years and above (at least 60% of the patients at each centre were required to be age 65 or older)

  • treated with diet alone for their diabetes for at least 12 weeks before randomisation

  • HbA1c from 6.5% to 10% inclusive

  • FPG greater than 140 mg/dl 2 weeks before randomisation

  • able to understand and comply with diet and glucose monitoring guidelines

EXCLUSION CRITERIA:

Serious illness that would prevent satisfactory completing of the study

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control 1: NR

Control 2: NR

Control 3: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea:

Control 1: NR

Control 2: NR

Control 3: NR

Interventions

NUMBER OF STUDY CENTRES: 30

COUNTRY/LOCATION: USA

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: titrated during trial until week 40

GLYCAEMIC TARGET: FPG < 140 mg/dl

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, plasma glucose, serum insulin, lipid levels, albumin and glucose excursions

Study details

RUN‐IN PERIOD: 6 weeks

DURATION OF INTERVENTION: 56 weeks

DURATION OF FOLLOW‐UP: 56 weeks

STUDY TERMINATED BEFORE REGULAR END: yes

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "The objective of this study was to determine the safety, efficacy, and tolerability of the a‐glucosidase inhibitor miglitol vs. the sulfonylurea glyburide in the treatment of elderly patients with type 2 diabetes mellitus, inadequately controlled by diet alone."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Four hundred eleven (411) diet‐treated patients age 60 yr or greater were randomized to receive…"

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "Glyburide dose titration was doubly blinded by encapsulation of active tablets or inactive excipients, and by an automated, interactive (between investigators and sponsor) dispensing system that permitted upwards and downwards dose titration without the glyburide dose appearing on tablets or packaging."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

We assume the outcomes assessors were blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Loss to follow‐up not adequately described

Selective reporting (reporting bias)

Unclear risk

Primary and secondary outcomes not stated in published protocol or design article

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical company

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, adequate blinding
Kaku 2011

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind in the first trial period (24 weeks), thereafter open‐label (28 weeks)

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: liraglutide

Participants

INCLUSION CRITERIA:

  • T2DM treated with diet therapy with or without oral antidiabetic monotherapy for no less than 8 weeks (oral antidiabetic drugs: biguanide, sulphonylurea, alpha‐glucosidase inhibitor, insulin secretagogue or insulin sensitiser within the dose range approved in Japan. The dose of sulphonylureas was set to within a half of the maximum approved dose. The dose of glibenclamide in patients previously treated with oral antidiabetic drugs was set at 2.5 mg or lower in order to exclude participants who could not be controlled with glibenclamide within the dose range fixed in this trial).

  • HbA1C ≥ 7.0% and < 10%

  • BMI < 35.0 kg/m2

  • age ≥ 20 years

EXCLUSION CRITERIA:

  • treated with insulin within 12 weeks of the start of the study

  • receiving or expecting to receive systemic corticosteroids

  • known hypoglycaemia unawareness or recurrent major hypoglycaemia

  • any serious medical condition

  • pregnant or breastfeeding

DIAGNOSTIC CRITERIA: the diagnosis of T2DM was done clinically by each investigator

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: 77

Control: 166

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: 5/47/36

Control: 13/101/94

Interventions

NUMBER OF STUDY CENTRES: 75

COUNTRY/LOCATION: Japan

SETTING: outpatients

TREATMENT BEFORE STUDY: diet with or without oral antidiabetic monotherapy

TITRATION PERIOD: 2 weeks

GLYCAEMIC TARGET: HbA1c < 6.9%

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, FPG, postprandial glucose, body weight, waist circumference, lipids, biochemical variables, hypoglycaemia, adverse events

Study details

RUN‐IN PERIOD: 4 to 6 weeks

DURATION OF INTERVENTION: 52 weeks

DURATION OF FOLLOW‐UP: 52 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "We compared the safety and efficacy of liraglutide vs glibenclamide in patients with poorly controlled (HbA1c, 7.4–10.4%) type 2 diabetes."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "…, the subjects were randomly assigned at a 1:2 ratio to receive 1‐year treatment with glibenclamide 1.25–2.5 mg/day or liraglutide given as follows…"

The patients were randomised according to a randomisation list. The list was generated by a person in Trans Cocmos, Inc (information through correspondence)

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

The trial consisted of 2 periods; a double‐blind period with adequate blinding of participants and investigators. Quote: "The trial utilised a double‐dummy method whereby placebo liraglutide injections and placebo glibenclamide tablets were administered alongside active therapy."

The second trial period was open‐label

Blinding of outcome assessment (detection bias)
All outcomes

High risk

The outcomes assessors were not blinded. However, the data review and decision on handling data were performed before the data from the liraglutide antibodies were available (information from correspondence)

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss to follow‐up sufficiently described

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes clearly defined in protocol published at www.clinicaltrials.gov, and they are all assessed

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical company

Trials according to risk of bias

Unclear risk

Adequate sequence generation, unclear allocation concealment and blinding
Kamel 1997

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: we assume double‐blind, as a placebo group is included

INTERVENTIONS USED IN TRIALS:

Sulphonylurea 1: gliclazide

Sulphonylurea 2: glibenclamide

Control 1: acarbose

Control 2: metformin

Control 3: placebo

Participants

INCLUSION CRITERIA:

  • T2DM

  • 35 to 65 years of age

  • BMI < 35 kg/m2

  • HbAlc 7% to 9%

  • duration of diabetes > 6 months

EXCLUSION CRITERIA: NR

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea 1: NR

Sulphonylurea 2: NR

Control 1: NR

Control 2: NR

Control 3: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea 1: NR

Sulphonylurea 2: NR

Control 1: NR

Control 2: NR

Control 3: NR

Interventions

NUMBER OF STUDY CENTRES: NR

COUNTRY/LOCATION: Turkey

SETTING: NR

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: NR

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): FPG, HbA1c, postprandial serum insulin level, fasting serum‐insulin levels and C‐peptide

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 24 weeks

DURATION OF FOLLOW‐UP: 24 weeks

STUDY TERMINATED BEFORE REGULAR END: NR

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING: NR

PUBLICATION STATUS: abstract in peer‐reviewed journal

Stated aim of study

Quote: "This study was planned to compare the different oral antidiabetic agents in NIDDM patients with dietary failure."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "43 NIDDM patients (35‐65 years of age, BMI< 35 kg/m2, HbA1c 7‐9%, duration of diabetes > 6 months) were randomized into five groups and treated for 24 weeks..."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

NR, but we assume double‐blinded because of placebo group

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NR

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

NR

Selective reporting (reporting bias)

Unclear risk

No design article or protocol available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Unclear risk

Funding not reported

Trials according to risk of bias

Unclear risk

Unclear sequence generation, allocation concealment and blinding
Kanda 1998

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: gliclazide

Control: acarbose

Participants

INCLUSION CRITERIA:

  • T2DM

  • not responding to strict diet and exercise treatment

  • fasting glucose level was higher than 150 mg/dl

  • BMI ≥ 24.5 kg/m2

  • Fasting plasma insulin levels ≥ 10µU/ml

EXCLUSION CRITERIA: NR

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: Japan

SETTING: NR

TREATMENT BEFORE STUDY: NR

TITRATION PERIOD: NR

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): waist size, visceral and subcutaneous fat

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 12 months

DURATION OF FOLLOW‐UP: 12 months

STUDY TERMINATED BEFORE REGULAR END: NR

Publication details

LANGUAGE OF PUBLICATION: Japanese

COMMERCIAL FUNDING: no

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "To compare effects of sulphonylurea and alpha‐glucosidase inhibitor (acarbose) on glucose and lipid metabolism in DM patients."

Notes

Evaluated by Japanese extractor

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"...randomised.."

Method not described

Allocation concealment (selection bias)

Low risk

Envelope used

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Assume not blinded

Incomplete outcome data (attrition bias)
All outcomes

High risk

Loss to follow‐up not addressed

Selective reporting (reporting bias)

Unclear risk

No design article or protocol available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Low risk

No funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Unclear sequence generation, adequate allocation concealment and inadequate blinding
Kovacevic 1997

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: single‐blind regarding acarbose versus glibenclamide, double‐blind regarding acarbose versus placebo

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control 1: acarbose

Control 2: placebo

Participants

INCLUSION CRITERIA:

  • T2DM for more than 3 months

  • HbA1c between 7% to 11%

  • age 35 to 70 years

  • stable body weight

  • BMI ≤ 35 kg/m2

EXCLUSION CRITERIA:

  • severe liver disease

  • severe kidney disease:

  • other severe disease

  • pregnancy

  • on concurrent laxative or obstipating medications

  • non‐compliance

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control 1: NR

Control 2: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control 1: NR

Control 2: NR

Interventions

NUMBER OF STUDY CENTRES: NR

COUNTRY/LOCATION: Croatia

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: titrated during trial

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, relative postprandial serum insulin increase, blood glucose (fasting, 1‐hour postprandial), fasting serum insulin, 1‐hour postprandial serum insulin, urine glucose, biochemical parameters

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 24 weeks

DURATION OF FOLLOW‐UP: 24 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING: NR

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "The study was designed as a multicentric, randomized group comparison between acarbose and placebo as a double‐blind, and between acarbose and glibenclamide as single‐blind trial."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "On entering the study, the patients were consecutively allocated a number and divided into groups."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Quote: "…between acarbose and placebo as a double‐blind, and between acarbose and glibenclamide as single‐blind trial."

However, the prescription of tablets are different in the acarbose group (tablets given 3 times a day) compared to the placebo group (tablets given 2 times a day)

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NR

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Loss to follow‐up adequately described

Selective reporting (reporting bias)

Unclear risk

No design article or study protocol available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Unclear risk

Funding not reported

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding of participants and investigators, unclear blinding of outcome assessors

Lawrence 2004

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: gliclazide

Control 1: metformin

Control 2: pioglitazone

Participants

INCLUSION CRITERIA:

  • 45 to 80 years

  • diet treated diabetes with an HbA1c > 7% or those on low‐dose oral hypoglycaemic therapy (gliclazide up to 80 mg/day or equivalent or metformin 500 mg 3 times a day) with an HbA1c < 7.5 %

  • BMI > 27 kg/m2

  • women of childbearing age had to be sterilised or using reliable contraceptive

EXCLUSION CRITERIA:

  • diet‐treated with an HbA1c > 10%

  • currently taking lipid‐lowering therapy

  • previous intolerant of any study medication

  • study medication would be contraindicated (alanine transaminase more than 3 times the upper limit of normal, a serum creatinine > 150 µmol/L or a history of heart failure)

  • resent acute myocardial infarction (< 3 months)

  • uncontrolled angina or uncontrolled hypertension

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control 1: NR

Control 2: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control 1: NR

Control 2: NR

Interventions

NUMBER OF STUDY CENTRES: NR

COUNTRY/LOCATION: United Kingdom

SETTING: outpatients

TREATMENT BEFORE STUDY: diet or low‐dose oral hypoglycaemic drugs

TITRATION PERIOD: 3 months

GLYCAEMIC TARGET: FBG < 7 mmol/L

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): lipids and biochemical variables

Study details

RUN‐IN PERIOD: 3 months

DURATION OF INTERVENTION: 24 weeks

DURATION OF FOLLOW‐UP: 24 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "To compare effects of different oral hypoglycemic drugs as first‐line therapy on lipoprotein subfractions in type 2 diabetes."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "...patients were randomly assigned.."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "Individual three‐digit patient identification numbers ensured that the laboratory staff was blinded to treatment allocation."

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All drop‐outs sufficiently described

Selective reporting (reporting bias)

Unclear risk

No study protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical company

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding of participants and investigators, adequate blinding of outcome assessors

LEAD‐3 2006

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind in the first year, thereafter open‐label extension

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glimepiride

Control 1: liraglutide 1.2 mg

Control 2: liraglutide 1.8 mg

Participants

INCLUSION CRITERIA:

  • T2DM

  • aged 18 to 80 years

  • BMI of 45 kg/m2 or less

  • eligible patients had been treated with diet and exercise or up to half the highest dose of oral antidiabetic drug monotherapy including sulphonylureas, meglitinide, aminoacid derivatives, biguanides, alpha‐glucosidase inhibitors and thiazolidinediones (1500 mg metformin or 30 mg pioglitazone were allowed) for at least 2 months

  • screening HbA1c value of 7% to 11% if treated with diet and exercise or 7% to 10% with oral antidiabetic monotherapy

EXCLUSION CRITERIA:

  • insulin treatment during the previous 3 months (except short‐term treatment for intercurrent illness)

  • treatment with systemic corticosteroids

  • hypoglycaemia unawareness or recurrent severe hypoglycaemia

  • impaired liver function (aspartate aminotransferase or alanine aminotransferase concentrations ≥ 2.5 times upper normal range)

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control 1: NR

Control 2: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control 1: NR

Control 2: NR

Interventions

NUMBER OF STUDY CENTRES: 138

COUNTRY/LOCATION: USA and Mexico

SETTING: outpatients

TREATMENT BEFORE STUDY: diet or half the highest dose of oral monotherapy for at least 2 months

TITRATION PERIOD: 2 to 3 weeks

GLYCAEMIC TARGET: HbA1c < 7%

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, body weight, FPG, self measured 8‐point plasma‐glucose profiles (measured before each meal, 90 min after the start of each meal, at bedtime and at 0300 h), blood pressure, ß‐cell function (proinsulin to insulin ratio and 2 models of B‐cell function: homoeostasis model assessment ‐B and homoeostasis model assessment‐insulin resistance), fasting glucagon and patients’ reported assessment of quality of life

Study details

RUN‐IN PERIOD: none

DURATION OF INTERVENTION: 195 weeks

DURATION OF FOLLOW‐UP: 195 weeks

STUDY TERMINATED BEFORE REGULAR END: yes. The duration of the treatment period was planned to be 260 weeks (5 years).

Quote: "The trial was terminated at week 195 due to an insufficient number of subjects remaining to obtain reasonable statistical power.”

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "We aimed to investigate the safety and efficacy of liraglutide as monotherapy for this disorder."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Randomisation was done with telephone‐based or web‐based systems. Participants were randomly assigned to the lowest available number."

Allocation concealment (selection bias)

Low risk

Quote: "Randomisation was done with telephone‐based or web‐based systems. Participants were randomly assigned to the lowest available number."

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

The first year of the trial had adequate blinding of participants and personnel. Blinding of participants and personnel was not possible in the open‐label extension

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Outcomes are assessed in the open‐label extension period and we therefore assume that the outcome assessors were not blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Some patients were lost to follow‐up, when the trial went from double‐blind to open‐label extension and between the open‐label extensions without being clearly described. All loss to follow‐up adequately described during the intervention periods

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes predefined in the study protocol are assessed

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Adequate sequence generation and allocation concealment, unclear blinding of participants and investigators, inadequate blinding of outcome assessors

Madsbad 2001

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glipizide

Control: repaglinide

Participants

INCLUSION CRITERIA:

  • diet or oral hypoglycaemic agents treated patients with T2DM

  • aged 40 to 75 years

  • BMI > 21 and < 35 kg/m2

  • HbA1c > 6.5 (diet‐treated) and < 10% (for patients previously on oral antidiabetic drugs)

EXCLUSION CRITERIA:

  • serum‐creatinine levels > 140 µmol/L

  • signs of liver disease

  • proliferative retinopathy

  • severe uncontrolled hypertension (defined as systolic blood pressure > 200 mmHg or diastolic blood pressure > 110 mmHg)

  • pregnancy

  • use of corticosteroids

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 23

COUNTRY/LOCATION: Denmark, Sweden, Norway and Finland

SETTING: outpatients

TREATMENT BEFORE STUDY: diet or oral antidiabetic drugs

TITRATION PERIOD: 6 weeks
GLYCAEMIC TARGET: FPG between 4.4 and 7.8 mmol/L

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, FBG, fasting C‐peptide, insulin, triglycerides, total cholesterol, HDL‐cholesterol, safety endpoints

Study details

RUN‐IN PERIOD: 1 week

DURATION OF INTERVENTION: 12 months + 6 to 8 weeks

DURATION OF FOLLOW‐UP: 12 months + 6 to 8 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "To evaluate the long‐term effectiveness and safety of repaglinide, a novel prandial glucose regulator, in comparison with glipizide in the treatment of patients with Type 2 diabetes."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Patients were randomized to treatment with repaglinide or glipizide at a 2:1 ratio (in order to test rigorously the safety of the relatively new agent repaglinide)” OR "One week later the patients were randomized to either repaglinide or glipizide following cessation of any previous antidiabetic medication."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "Placebo tablets were used in the glipizide group for lunch and dinner."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

We assume the outcome assessors were blinded due to a double‐blind design

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Adequate description of patients lost to follow‐up

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes assessed as predefined

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, adequate blinding
Marbury 1999

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: repaglinide

Participants

INCLUSION CRITERIA:

  • age 37 to 75 years

  • BMI of 20 to 40 kg/m2

  • T2DM according to WHO criteria of at least 6 months’ duration

  • diet/exercise or another oral antidiabetic agent

  • HbA1c 6.5% to 14.6% (diet‐treated with HbA1c > 6.5%, oral hypoglycaemic treated with HbA1c < 12%)

EXCLUSION CRITERIA:

  • chronic insulin use

  • severe, uncontrolled hypertension

  • cardiac disorders

  • proliferative retinopathy

  • elevated serum creatinine (> 1.6 mg/dl), aspartate aminotransferase (> 120 U/L) or alanine aminotransferase (> 195 U/L) levels.

  • contraindications to glyburide

  • previously receiving repaglinide or systemic corticosteroids

DIAGNOSTIC CRITERIA: WHO criteria

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: 2

Control: 11

Interventions

NUMBER OF STUDY CENTRES: 21

COUNTRY/LOCATION: USA and Canada

SETTING: outpatients

TREATMENT BEFORE STUDY: diet or oral antidiabetic (other than repaglinide)

TITRATION PERIOD: 8 weeks

GLYCAEMIC TARGET: FPG 80 to 140 mg/dl, HbA1c ≤ 7.5%

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, FPG, lipid metabolism, changes in body weight and safety profiles, including hypoglycaemic events

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 12 months

DURATION OF FOLLOW‐UP: 12 + 3 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "This prospective, 1‐year, multicenter, double‐blind, randomized, parallel‐group study was designed to show that repaglinide was at least equivalent to glyburide in patients with type 2 diabetes."

Notes

Number with previously cardiovascular disease is the number of participants with previously serious cardiac events

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Patients were randomized within each study center in a 2:1 ratio of repaglinide and glyburide and discontinued OHAs on the morning of the first post randomization visit."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "Glyburide patients received a starting dose of 2.5 mg before breakfast and placebo before
lunch and dinner"

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

We assume the outcome assessors were blinded due to a double‐blind design

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss to follow‐up sufficiently described

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes assessed as predefined

Academic bias

High risk

First author has published similar trials (Damsbo 1999)

Sponsor bias

High risk

Received funding from pharmaceutical industry

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, adequate blinding
Memisogullari 2009

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: gliclazide

Control: nothing

Participants

INCLUSION CRITERIA:

  • T2DM

  • recently diagnosed

EXCLUSION CRITERIA:

  • active inflammatory and infectious diseases

  • anti‐inflammatory, antihyperlipidaemic or antihypertensive drugs

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR/0/0

Control: NR/0/0

Interventions

NUMBER OF STUDY CENTRES: NR

COUNTRY/LOCATION: Turkey

SETTING: outpatients

TREATMENT BEFORE STUDY: NR

TITRATION PERIOD: NR

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): glycaemic control, markers of inflammation

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 6 months

DURATION OF FOLLOW‐UP: 6 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING: NR

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "In this study, we aimed to investigate whether gliclazide or diet treatment has an effect on serum levels of acute phase reactants, markers of inflammation."

Notes

The group of healthy controls is not included in the analyses

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Twenty‐six patients were prospectively randomized to take gliclazide…"

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

We assume not blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Number lost to follow‐up not reported

Selective reporting (reporting bias)

Unclear risk

No design article or study protocol

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Unclear risk

NR

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Nakamura 2004

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: NR, we assume open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Comparator 1: pioglitazone

Comparator 2: voglibose

Participants

INCLUSION CRITERIA:

  • no history of ketoacidosis

  • treatment by diet alone

  • fasting C‐peptide level more than 0.33 mmol/L

  • HbA1c level more than 6.5%

EXCLUSION CRITERIA:

  • serum creatinine in excess of 1.5 mg/dl

  • none of the patients had been given antihypertensive drugs, including angiotensin‐converting enzyme inhibitors

  • no malignancy, heart disease, cerebrovascular disease, liver disease or collagen disease based on physical examinations, urine and blood examination, and radiography, electrocardiography, ultrasound cardiography, x‐ray or computed tomography scan data

  • haematuria or casturia

  • history of nondiabetic renal disease

DIAGNOSTIC CRITERIA: WHO

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Comparator: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR/0/NR

Comparator: NR/0/NR

Interventions

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: Japan

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: NR

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): urinary albumin excretion, intima‐media thickness, pulse wave velocity, HbA1c

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 12 months

DURATION OF FOLLOW‐UP: 12 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING: NR

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "The aim of the present study was to compare the effects of pioglitazone (amelioration of insulin resistance), sulfonylurea (augmentation of insulin supply), and voglibose (limitation of postprandial hyperglycemia) on UAE, IMT, and PWV in normotensive diabetes patients with microalbuminuria."

Notes

Group of healthy controls are not included in the analyses

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "The patients were randomly assigned to 1 of 3 treatment groups by sealed envelop method: treatment with pioglitazone 30 mg/d (n = 15), treatment with glibenclamide 5 mg/d (n = 15), or treatment with voglibose 0.6 mg/d (n = 15)"

Allocation concealment (selection bias)

Low risk

Quote: "The patients were randomly assigned to 1 of 3 treatment groups by sealed envelop method: treatment with pioglitazone 30 mg/d (n = 15), treatment with glibenclamide 5 mg/d (n = 15), or treatment with voglibose 0.6 mg/d (n = 15)"

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Blinding not reported, we assume open‐label

Blinding of outcome assessment (detection bias)
All outcomes

High risk

NR, we assume not blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote: "There were no dropouts throughout the study period"

Selective reporting (reporting bias)

Low risk

All outcomes reported

Academic bias

High risk

Nakamura 2000

Sponsor bias

Unclear risk

NR

Trials according to risk of bias

Unclear risk

Unclear sequence generation, adequate allocation concealment, unclear blinding
Nakamura 2006

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Comparator 1: pioglitazone

Comparator 2: voglibose

Comparator 3: nateglinide

Participants

INCLUSION CRITERIA:

  • no history of ketoacidosis

  • treatment by diet alone

  • fasting C‐peptide level of more than 0.33 mmol/L

  • HbA1c more than 6.5%

  • microalbuminuria

EXCLUSION CRITERIA:

  • serum creatinine in excess of 1.5 mg/dL

  • none of the patients had been given antihypertensive drugs, including angiotensin‐converting enzyme inhibitors, angiotensin receptor blocker or anti‐platelet drugs

  • no malignancy, heart disease, cerebrovascular disease, liver disease or collagen disease based on physical examinations, urine and blood examination, and radiography, electrocardiography, ultrasound cardiography, x‐ray or computed tomography scan data

  • haematuria or casturia

  • known history of nondiabetic renal disease

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Comparator: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: 0/0/0

Comparator: 0/0/0

Interventions

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: Japan

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: 3 months

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): glucose, HbA1c, creatinine, urea nitrogen, total cholesterol, high density lipoprotein cholesterol, triglyceride and urinary albumin excretion

Study details

RUN‐IN PERIOD: 3 months

DURATION OF INTERVENTION: 12 months

DURATION OF FOLLOW‐UP: 12 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING: no

NON‐COMMERCIAL FUNDING: Shinmatsudo Central General Hospital and Koto Hospital

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "The aim of the present study was to determine whether pioglitazone affects urinary L‐FABP levels in diabetic nephropathy patients with microalbuminuria."

Notes

Group of healthy controls are not included in the analyses

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "The diabetes patients with microalbuminuria were randomly assigned to one of four treatment groups by the sealed envelope method: treatment with pioglitazone 30 mg/d (n = 17), with glibenclamide 5 mg/d (n = 18), with voglibose 0.6 mg/d (n = 17), or with nateglinide 270 mg/d (n = 16)."

The randomisation sequence was made by computer

Allocation concealment (selection bias)

Low risk

See above

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Participants and investigators were blinded. Information through correspondence

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Outcomes assessors were blinded. Information through correspondence

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote: "..., and there were no dropouts."

Selective reporting (reporting bias)

High risk

Primary and secondary outcomes reported by author, but not described in publication

Academic bias

High risk

Nakamura 2000; Nakamura 2004

Sponsor bias

Low risk

No commercial funding

Trials according to risk of bias

Low risk

Adequate sequence generation, allocation concealment and blinding
Nathan 1988

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: insulin

Participants

INCLUSION CRITERIA:

  • T2DM

  • 30 to 70 years

  • weight greater than 90% of ideal weight

  • willingness and ability to do self blood glucose monitoring

  • patients not achieving FBG less than 7.8 mmol/L and HbA1c less than 6.5% after 1 month of diet were randomised

EXCLUSION CRITERIA:

  • treated with insulin or oral agents within the last 6 months or have ever been primary or secondary oral agents failures

  • women planning pregnancy

  • history of renal failure

  • active liver disease

  • allergy to insulin, sulphonylurea or other sulphonamide drugs

DIAGNOSTIC CRITERIA: National Diabetes Data Group

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: USA

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: titrated during trial

GLYCAEMIC TARGET: FBG < 6.4 mmol/L without hypoglycaemia

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): efficacy and complications, lipid status and weight

Study details

RUN‐IN PERIOD: 1 month

DURATION OF INTERVENTION: 9 months

DURATION OF FOLLOW‐UP: 9 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "To compare the relatively efficacy, risks, and benefits of insulin with glyburide in achieving normoglycaemia in non‐insulin‐dependent diabetes mellitus."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "……were randomly assigned to either glyburide or NPH insulin therapy using a computer‐generated list."

Allocation concealment (selection bias)

Low risk

Quote: "……were randomly assigned to either glyburide or NPH insulin therapy using a computer‐generated list."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "Glyburide (5‐mg tablets) and identical placebo tablets were supplied by the manufacturer..."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "The success of the double‐blind treatment strategy was tested by asking the research nurse and patient to guess.."

We assume that the nurses were the outcome assessors

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No participants were lost to follow‐up

Selective reporting (reporting bias)

Unclear risk

No design article or study protocol available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical company

Trials according to risk of bias

Low risk

Adequate sequence generation, allocation concealment and blinding
Pagano 1995

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: miglitol

Participants

INCLUSION CRITERIA:

  • T2DM

  • treated with diet and/or biguanide (biguanide discontinued at least 2 months before inclusion)

EXCLUSION CRITERIA:

  • age < 40 years or > 70 years

  • BMI > 30 kg/m2

  • HbA1c < 7% or > 11%

  • previous antidiabetic treatment (except biguanides)

  • serum creatinine > 176.8 mmol/L

  • haemoglobin > 11 g/dl

DIAGNOSTIC CRITERIA: National Diabetes Group Criteria

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 4

COUNTRY/LOCATION: Italy

SETTING: outpatients

TREATMENT BEFORE STUDY: diet or biguanides (discontinued at least 2 months before inclusion in trial)

TITRATION PERIOD: 6 weeks

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, meal‐stimulated serum insulin and C‐peptide, FBG, postprandial glucose, total and HDL cholesterol, triglycerides, side effects and compliance

Study details

RUN‐IN PERIOD: 7 weeks

DURATION OF INTERVENTION: 6 months

DURATION OF FOLLOW‐UP: 6 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English and Italian

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "The purpose of the present study was to compare the effectiveness of miglitol and glibenclamide in reducing HbA1c during long‐term (24 week) administration in Type 2 diabetic patients (5‐7) as well as meal‐stimulated serum insulin and C‐peptide levels (8, 9)."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "…, patients were randomly assigned to miglitol…."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "The glibenclamide group received a breakfast placebo throughout the study."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

We assume they were blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Not described to which group patients lost to follow‐up belonged

Selective reporting (reporting bias)

Unclear risk

No design article or protocol available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical company

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, adequate blinding
Perriello 2007

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: gliclazide

Control: pioglitazone

Participants

INCLUSION CRITERIA:

  • T2DM managed by diet alone or with a maximum of one glucose‐lowering agent

  • aged 35 to 70 years

  • HbA1C > 7.5%

  • no history of major cardiovascular events (myocardial infarction or stroke) within the 12 months before enrolment

EXCLUSION CRITERIA: described in inclusion criteria

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: 0

Control: 0

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 33

COUNTRY/LOCATION: Italy

SETTING: outpatients

TREATMENT BEFORE STUDY: diet or maximum of 1 oral hypoglycaemic agent

TITRATION PERIOD: drugs were titrated every month to achieve glycaemic target

GLYCAEMIC TARGET: the dose of drugs was increased if FBG was > 7.5 mmol/L or HbA1c > 7.5%

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, FBG, insulin and homeostasis model assessment of insulin resistance, self monitoring blood glucose, changes in plasminogen activator‐1, antithrombin‐III, von Willebrand factor and platelets

Study details

RUN‐IN PERIOD: 2 weeks

DURATION OF INTERVENTION: 1 year

DURATION OF FOLLOW‐UP: 1 year

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "To compare long‐term (1 year) efficacy and safety of pioglitazone and gliclazide in patients with Type 2 diabetes."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Patients were randomised to receive either pioglitazone 30–45 mg/day or gliclazide 80–320 mg/day for up to one year."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "In order to assure the double‐blindness, drugs or placebo were identical in weight, taste, colour and shape and kept in coloured bottles with increasing doses of drugs. The lower doses of pioglitazone (30 mg) or gliclazide (80 mg) were stored in red bottles along with the placebo; 45 mg of pioglitazone and placebo or 80 and 160 mg of gliclazide were kept in blue and yellow bottles."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Double‐blind design. We assume the outcomes assessors were blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Drop‐outs sufficiently described

Selective reporting (reporting bias)

Unclear risk

Primary and secondary outcomes clearly defined and assessed in publication, but no design article or study protocol available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received support from a pharmaceutical company

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, adequate blinding
Rosenthal 2002

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: blinding not described, but we assume open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: acarbose

Participants

INCLUSION CRITERIA:

  • T2DM

  • men: age 40 to 75

  • female: age < 75 (postmenopausal)

  • overweight

  • mild hypertension

EXCLUSION CRITERIA:

  • myocardial infarction within the last 3 months

  • type 1 diabetes

  • alcohol or drug abuse

  • severe liver disease

  • serum creatinine > 1.3 mg/dl

  • hypo/or hyperthyroidism

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: USA

SETTING: outpatients

TREATMENT BEFORE STUDY: oral antidiabetic intervention or diet

TITRATION PERIOD: titrated during trial

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): blood pressure, serum insulin and biochemical variables

Study details

RUN‐IN PERIOD: 4 weeks

DURATION OF INTERVENTION: 6 months

DURATION OF FOLLOW‐UP: 6 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "To investigate the relationship between hypertension and hyperinsulinaemia, the effects on blood pressure and insulin levels of two oral antidiabetic agents with different mechanisms of action, acarbose (an α‐glucosidase inhibitor) and glibenclamide (an insulin promoter), were compared in patients with hypertension and type 2 diabetes mellitus."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "This study had a randomised, controlled, parallel‐group design"

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

We assume open‐label

Blinding of outcome assessment (detection bias)
All outcomes

High risk

NR, we assume not blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

13 patients excluded due to protocol deviations

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

First article

Sponsor bias

High risk

Received funding from pharmaceutical company

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Salman 2001

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: gliclazide

Control: acarbose

Participants

INCLUSION CRITERIA:

  • T2DM ≥ 3 months

  • age 35 to 70 years

  • previously treated by diet alone

  • BMI ≤ 35 kg/m2

  • stable body weight

  • HbA1c 8% to 10%

  • C‐peptide > 0.2 nmol/L

  • capable and willing to give informed consent

EXCLUSION CRITERIA:

  • hypersensitivity to acarbose or gliclazide

  • inability to complete the study because of any significant disease or condition

  • having severe and poorly controlled diabetes manifested by ketonuria or severe hyperglycaemia and progressive weight loss, or documented gastrointestinal disease which was likely to be associated with abnormal gut motility or altered absorption of nutrients

  • receiving any investigational drug or participating in any other clinical trial within the last 30 days

  • receiving medication that significantly alters gastrointestinal motility and/or absorption

  • under therapy with any medication known to affect glucose homeostasis

  • had impaired liver functions defined as alanine‐aminotransferase or aspartate transaminase of more than twice the upper limits of normal

  • impaired kidney function (serum creatinine > 220 µmol/L)

  • woman of childbearing age not using contraception or who was either pregnant or nursing

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: Turkey

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: 4 weeks

GLYCAEMIC TARGET: not directly described, but they use HbA1c levels < 8% as a success criteria in the results section

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): fasting and postprandial plasma insulin, C‐peptide, glucose levels, HbA1C, lipid profiles, biochemical tests for evaluation of drug safety

Study details

RUN‐IN PERIOD: 4 weeks

DURATION OF INTERVENTION: 24 weeks

DURATION OF FOLLOW‐UP: 24 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "To compare the effect of acarbose and gliclazide on clinical findings, biochemical parameters and safety in type 2 diabetic patients insufficiently controlled with medical nutrition therapy (MNT)."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Seventy‐two patients (age 35–70 years, BMI ≤ 35 kg/m2), who had not taken any oral antidiabetic drug previously, were randomised into two groups after a four‐week placebo period, and treated for 24 weeks with acarbose (100 mg two to three times daily) and gliclazide (40–80 mg twice daily)."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

We assume not blinded due to open‐label design

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Loss to follow‐up not adequately described

Selective reporting (reporting bias)

Unclear risk

Outcomes clearly defined in trial publication, but not in a published protocol or design article

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical company

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Segal 1997

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control 1: miglitol

Control 2: placebo

Participants

INCLUSION CRITERIA:

  • 30 to 70 years of age

  • T2DM of at least 3 months' duration

  • stable body weight on diet alone

  • no other diabetes medication in the 3 months before randomisation

  • HbA1c between 7.5% and 9.5%

  • absence of other major illness

EXCLUSION CRITERIA: NR

DIAGNOSTIC CRITERIA: WHO

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control 1: NR

Control 2: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control 1: NR

Control 2: NR

Interventions

NUMBER OF STUDY CENTRES: 18

COUNTRY/LOCATION: Austria, Germany, Israel and Czech Republic

SETTING: outpatients

TREATMENT BEFORE STUDY: treatment‐naive

TITRATION PERIOD: 4 weeks

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, biochemical variables

Study details

RUN‐IN PERIOD: 4 weeks

DURATION OF INTERVENTION: 24 weeks

DURATION OF FOLLOW‐UP: 24 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "To compare the therapeutic effects of the alpha‐glucosidase inhibitor miglitol (BAY m 1099), the sulfonylurea glibenclamide, and placebo on parameters of metabolic control and safety in patients with NIDDM that is inadequately controlled by diet alone."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Randomization of eligible patients into a miglitol, glibenclamide (Euglucon, Boehringer Mannheim), and placebo treatment groups took place after a 4‐week single‐blind double‐placebo run‐in period, if the patient was at least 80% compliant."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote: "Patients randomized to the three treatment groups received double‐blind, double‐dummy treatment."

However, the titration regimen and the opportunity to increase the dose differed for the investigator, depending on the randomised intervention

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

See above

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

There were many drop‐outs and a very sparse description of the reasons

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes are reported

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Several authors work in the pharmaceutical industry

Trials according to risk of bias

Unclear risk

Unclear sequence generation, allocation concealment and blinding
Shihara 2011

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glimepiride

Control: pioglitazone

Participants

INCLUSION CRITERIA:

  • T2DM

  • 30 to 75 years

  • stable dietary and exercise regime at least 1 month before randomisation

  • HbA1c between 6.9% to 10.4% at randomisation and 1 month before randomisation with absolute difference < 1% between these measurements

EXCLUSION CRITERIA:

  • type 1 diabetes

  • use of insulin or any oral antidiabetic intervention in the month before randomisation

  • heart failure

  • any serious intercurrent complication involving heart, kidney, liver, pancreas or other organs or haematological condition

  • women who are pregnant, wishing to become pregnant or lactating

  • excessive alcohol drinking

  • past history of drug allergies

  • participating in other clinical studies (excluding epidemiological studies)

  • determined inappropriate for the study by the investigator

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 33

COUNTRY/LOCATION: Japan

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: titrated during trial

GLYCAEMIC TARGET: FBG < 120 mg/dL, but > 80 mg/dl

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): percentage of patients with HbA1c < 6.9 at the end of study, change in HbA1c at 6 months compared with baseline, fasting plasma glucose, insulin, lipids and plasma natriuretic peptide levels, body weight, BMI, safety of study medication, compliance

Study details

RUN‐IN PERIOD: 1 month

DURATION OF INTERVENTION: 6 months

DURATION OF FOLLOW‐UP: 6 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "To compare first‐line agent glimepiride and pioglitazone in Japanese patients with type 2 diabetes uncontrolled by diet and exercise with respect to glycaemic control, safety and metabolic changes."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Randomization was carried out by a central registration method."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

In protocol described that no one was blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All loss to follow‐up explained

Selective reporting (reporting bias)

High risk

Assessed primary and secondary outcomes, but had in protocol predefined per cent of patients achieving HbA1c < 6.5%, however only reports the per cent of patients achieving HbA1c < 6.9%

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Pharmaceutical funding

Trials according to risk of bias

Unclear risk

Inadequate sequence generation, unclear allocation concealment, inadequate blinding
Spengler 1992

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: acarbose

Participants

INCLUSION CRITERIA:

  • T2DM insufficiently treated with diet

  • FBG ≥ 7.8 mmol/L, 1 hour postprandial glucose ≥ 10 mmol/L

  • diabetes duration ≥ 2 months

  • age 40 to 70 years

  • Broca‐index ≤ 1.3

EXCLUSION CRITERIA:

  • patients who could not co‐operate

  • patients who were unlikely to complete the trial

  • previously treated with peroral antidiabetics or insulin

  • myocardial infarction within the last 6 months

  • severe liver or kidney disease (creatinine > 2 mg/dl)

  • disease in the haemopoietic system

  • malignant tumours

  • enteropathy

  • infections with fever

  • pregnancy

  • alcohol or nicotine abuse

  • taking part in another clinical trial

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 7

COUNTRY/LOCATION: Germany

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: glibenclamide titrated during the trial, the dose of acarbose was doubled after 2 weeks.

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): FBG and 1 hour after breakfast, HbA1c, triglycerides, cholesterol, body weight, blood pressure, subjective symptoms, biochemical variables

Study details

RUN‐IN PERIOD: none

DURATION OF INTERVENTION: 24 weeks

DURATION OF FOLLOW‐UP: 24 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English and German

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "This was the rationale to investigate the efficacy of acarbose vs. glibenclamide in a 6 months group comparison."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "The patients were in each centre consecutively assigned to one of two treatment groups according to a list of random numbers (after principle of randomness)."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

We assume not blinded due to open‐label design

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Reasons for drop‐outs clearly described, but it is not possible to estimate to which intervention they were originally randomised. The participants lost to follow‐up are not included in the analysis

Selective reporting (reporting bias)

Unclear risk

Primary and secondary outcomes not clearly described. No design article or protocol available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical company

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Sung 1999

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: not described, we assume open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: troglitazone

Participants

INCLUSION CRITERIA:

T2DM with fasting glucose ≥ to 7.8 mmol/L and < 16.7 mmol/L on > 2 separate occasions

EXCLUSION CRITERIA:

  • smokers

  • hypertension

  • known cardiovascular disease

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: NR

COUNTRY/LOCATION: USA

SETTING: outpatients

TREATMENT BEFORE STUDY: NR

TITRATION PERIOD: NR

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): haemodynamic mechanism of blood pressure lowering glucose, insulin, C‐peptide and HbA1c. Resting and stress blood pressure, stroke volume and cardiac output

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 6 months

DURATION OF FOLLOW‐UP: 6 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "The present study examined the hemodynamic mechanisms of blood pressure (BP) lowering by troglitazone in patients with type 2 diabetes mellitus (DM) at rest and during a mental arithmetic test (MAT)."

Notes

"This study was performed as a 2‐part protocol. The first part was to compare BP response to a mental arithmetic test (MAT) in persons with and without DM. Twenty‐two DM patients and 12 age‐ and gender‐matched controls participated in this protocol. The second part was designed to compare metabolic and hemodynamic effects of troglitazone and glyburide in subjects with DM. The same 22 DM patients were randomized to either the troglitazone or glyburide group and treated for 6 months"

The healthy controls are not included

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "The DM group was then randomized to receive…"

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Unlikely, not mentioned

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Unlikely

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

No drop‐outs accounted for. Due to the size of the study it is very likely that there were no drop‐outs

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Low risk

No funding from the pharmaceutical industry

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Sutton 2002

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Comparator: rosiglitazone

Participants

INCLUSION CRITERIA:

  • T2DM with endogenous insulin production (fasting C‐peptide ≥ 0.8 ng/ml)

  • 40 to 80 years

  • women had to be postmenopausal, surgically sterile or currently using hormonal contraceptives or intrauterine devices

  • FPG ≥ 140 mg/dl but ≤ 300 mg/dl after the run‐in period

EXCLUSION CRITERIA:

  • renal disease (serum creatinine level > 18 mg/dl)

  • hepatic disease

  • previous treatment of myocardial infarction

  • NYHA class III/IV, coronary insuffiencey, congestive heart failure

  • previous or existing treatment with angiotensin‐converting enzyme inhibitors, angiotensin II receptor antagonists, β‐blockers or calcium‐channel blockers

  • echocardiographic evidence of marked left ventricular hypertrophy at baseline

  • uncontrolled blood pressure (> 160/> 100)

  • FPG not within 140 and 300 mg/dl after 2 weeks of placebo treatment were excluded

DIAGNOSTIC CRITERIA: National Diabetes Data Group definition, with fasting C‐peptide concentration ≥ 0.8 ng/ml

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Comparator: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Comparator: NR

Interventions

NUMBER OF STUDY CENTRES: 19

COUNTRY/LOCATION: USA

SETTING: outpatients

TREATMENT BEFORE STUDY: varied from diet, single oral antidiabetic drug or combination therapy

TITRATION PERIOD: 8 weeks

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): change from baseline in Left Ventricular Mass Index at weeks 28 and 52, change from baseline in left ventricular end‐diastolic volume, ejection fraction, blood pressure, heart rate, arterial pressure, pulse, glycaemic control, serum lipids at weeks 28 and 52, urinary albumin excretion

Study details

RUN‐IN PERIOD: 4 weeks

DURATION OF INTERVENTION: 52 weeks

DURATION OF FOLLOW‐UP: 52 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "This open‐label, active‐controlled study investigated the cardiac safety and antihyperglycemic effect of rosiglitazone (RSG) in patients with type 2 diabetes."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Eligible patients were randomly assigned…"

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

We assume not blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Discrepancy in number lost to follow‐up in publication

Selective reporting (reporting bias)

Unclear risk

No design article or protocol

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received commercial funding

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Tan 2004

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glimepiride

Comparator: pioglitazone

Participants

INCLUSION CRITERIA:

  • HbA1c > 7.5% to ≤ 11% in patients who were not receiving oral antidiabetic drugs, and > 7.5% to ≤ 9.5% in patients who were receiving oral antidiabetic drugs monotherapy

  • adequate trial of dietary and lifestyle interventions before enrolment, as determined by the investigator

EXCLUSION CRITERIA:

  • treatment with a thiazolidinedione or insulin within the previous 3 months

  • current prescription for a maximum dose of an oral antidiabetic drugs or for combination

  • oral antidiabetic drugs therapy

  • treatment with systemic glucocorticoids (excluding topical and inhaled preparations) within the previous 30 days

  • cardiac disease with substantial limitation of functional capacity (NYHA Class III or IV)

  • serum triglycerides > 400 mg/dl (> 4.5 mmol/L)

  • serum creatinine > 2.0 mg/dl (> 177 µmol/L)

  • renal transplantation or current renal dialysis

  • alanine aminotransferase or aspartate aminotransferase levels > 2.5 times the upper limit of normal of the central laboratory

  • clinical signs or symptoms of liver disease

  • haemoglobin < 10.5 g/dl for women and 11.5 g/dl for men

  • previous human immunodeficiency virus infection

  • BMI < 25 kg/m2 or > 35 kg/m2

  • signs or symptoms of substance abuse

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Comparator: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR/NR/14

Comparator: NR/NR/15

Interventions

NUMBER OF STUDY CENTRES: 19

COUNTRY/LOCATION: Mexico

SETTING: outpatients

TREATMENT BEFORE STUDY: diet or monotherapy oral (not maximum dose)

TITRATION PERIOD: 12 weeks

GLYCAEMIC TARGET:

FBG ≤ 7 mmol/L and a 1‐hour postprandial blood glucose concentration ≤ 10 mmol/L

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): glycaemic control, insulin sensitivity and safety assessment

Study details

RUN‐IN PERIOD: 1 to 3 weeks

DURATION OF INTERVENTION: 52 weeks

DURATION OF FOLLOW‐UP: 52 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "The goals of this study were to compare changes in measures of glycemic control and insulin sensitivity in Mexican patients with type 2 diabetes who received pioglitazone or glimepiride for 1 year."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Patients who met the inclusion criteria were randomized in equal proportions to receive pioglitazone or glimepiride during the titration period according to a central randomization table generated by the sponsor and administered by an automated interactive voice‐response system."

Allocation concealment (selection bias)

Low risk

See above

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Quote: "All doses of both drugs were administered as a single capsule to ensure blinding."

However, according to the titration regimen pioglitazone could be prescribed in 3 tablets and glimepiride in 4 tablets. They have not reported use of placebo

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Description of all patients lost to follow‐up

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes reported

Academic bias

High risk

First author has published similar trials (Tan 2004a)

Sponsor bias

High risk

Received commercial funding

Trials according to risk of bias

Unclear risk

Adequate sequence generation and allocation concealment, unclear blinding
Tan 2004a

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Comparator: pioglitazone

Participants

INCLUSION CRITERIA:

  • oral antidiabetic drug‐naive or were currently receiving monotherapy for the treatment of their diabetes

  • HbA1c > 7.5% and < 11% for patients who were not receiving oral antidiabetic drugs, or > 7.5% and < 9.5% for patients receiving oral antidiabetic drug monotherapy

  • fasting serum C‐peptide of 0.333 pmol/L (1.0 ng/ml)

  • received an adequate trial of dietary/lifestyle intervention

EXCLUSION CRITERIA:

  • insulin treatment within 30 days

  • glucocorticoid therapy (excluding topical and inhaled preparations) within 4 weeks; current treatment with nicotinic acid

  • currently on a maximum dose of 1 oral antidiabetic drug or on combination oral antidiabetic drug therapy

  • cardiac disease with substantial limitation of functional capacity (NYHA Class III or IV cardiac status)

  • serum creatinine > 177 µmol/L (2.0 mg/dl)

  • renal transplant or current renal dialysis

  • clinical signs or symptoms of liver disease

  • alanine aminotransferase or aspartate aminotransferase > 2.5 times the upper limit of normal for the central laboratory

  • haemoglobin or hematocrit below the lower limit of normal for the central laboratory

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Comparator: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR/47/28

Comparator: NR/45/29

Interventions

NUMBER OF STUDY CENTRES: 22

COUNTRY/LOCATION: Denmark, Norway, Sweden and Finland

SETTING: outpatients

TREATMENT BEFORE STUDY: oral monotherapy (not maximum dose) or diet

TITRATION PERIOD: 12 weeks

GLYCAEMIC TARGET:

FBG of < 7 mmol/L (126 mg/dl) and 1‐h PBG of < 10 mmol/L (180 mg/dl)

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): efficacy and safety

Study details

RUN‐IN PERIOD: 1 to 3 weeks

DURATION OF INTERVENTION: 52 weeks

DURATION OF FOLLOW‐UP: 52 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "This study compared the effects of 52 weeks' treatment with pioglitazone, a thiazolidinedione that reduces insulin resistance, and glibenclamide, on insulin sensitivity, glycaemic control, and lipids in patients with Type 2 diabetes."

Notes

Not clearly reported in publication whether the trial is double‐blind or open‐label, but we assume open‐label, based on the different doses in the titration period

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Patients were randomized to receive pioglitazone or micronized glibenclamide."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinding not reported in the publication. Sponsor described the blinding; glibenclamide and pioglitazone tablets were put inside a capsule to ensure blinding. Dummy titration visit was made for pioglitazone to ensure blinding

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NR

Incomplete outcome data (attrition bias)
All outcomes

Low risk

There was a very high number of patients lost to follow‐up. The reasons for all of them were not clear in the publication, but additional information from the sponsors provided us with sufficient information

Selective reporting (reporting bias)

Low risk

All outcomes predefined in study protocol and reported

Academic bias

High risk

First author has published similar trials (Tan 2004)

Sponsor bias

High risk

Received commercial funding

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, adequate blinding of participants and investigators, unclear blinding of outcome assessors

Tan 2005

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind (extension of Charbonnel 2005)

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: gliclazide

Control: pioglitazone

Participants

INCLUSION CRITERIA: extension of Charbonnel 2005

EXCLUSION CRITERIA: extension of Charbonnel 2005

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 98 centres (selected on basis on the number of patients selected for the parent study)

COUNTRY/LOCATION: Australia, Canada, Finland, Poland, the Slovak Republic, United Kingdom and South Africa

SETTING: outpatients

TREATMENT BEFORE STUDY: before randomisation to initial double‐blind treatment phase, the patients were drug‐naive (Charbonnel 2005). The patients were receiving either gliclazide or pioglitazone before the extension trial

TITRATION PERIOD: none for the extension period

GLYCAEMIC TARGET: HbA1c < 8%

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): time to intervention failure, HbA1c, FPG, fasting serum insulin, homeostasis model assessment for insulin sensitivity and for cell activity

Study details

RUN‐IN PERIOD: none

DURATION OF INTERVENTION: 52 weeks

DURATION OF FOLLOW‐UP: 52 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "The hypothesis that pioglitazone treatment is superior to gliclazide treatment in sustaining glycemic control for up to 2 years in patients with type 2 diabetes was tested."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "This was a randomized, multicenter..."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "...randomized, multicenter, double‐blind, double‐dummy, parallel‐group,..."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

We assume the outcome assessors were blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Adequate description of patients lost to follow‐up

Selective reporting (reporting bias)

Unclear risk

No published protocol or design article available

Academic bias

High risk

Published similar trial previously (Tan 2004; Tan 2004a)

Sponsor bias

High risk

Received funding from pharmaceutical company

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, adequate blinding
Tang 2004

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: glimepiride

Comparator: metformin

Participants

INCLUSION CRITERIA:

  • T2DM

  • age 35 to 70 years

  • course of disease < 5 years, without ketosis in 6 months

  • BMI 22 to 29 kg/m2

  • been treated with fixed dose glimepiride and/or metformin for more than 4 weeks in order to elution the influence of other hypoglycaemic drugs

  • newly diagnosed patients with not ideal blood glucose control after diet and/or exercise therapy for 4 weeks (FBG ≥ 7.0 mmol/L and/or postprandial blood glucose ≥ 11.1 mmol/L)

  • not been treated with insulin

  • not been treated with lipid‐lowering drugs, thiazide diuretics, sex hormones, thyroxine, β‐blockers, etc. for at least 2 months

  • without complications of diabetes

  • without gastrointestinal, heart, liver or kidney diseases

EXCLUSION CRITERIA: described in the inclusion criteria

DIAGNOSTIC CRITERIA: WHO 1999

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: 13

Comparator: 13

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: 0/NR/0

Comparator: 0/NR/0

Interventions

NUMBER OF STUDY CENTRES: NR, probably 1

COUNTRY/LOCATION: China

SETTING: NR

TREATMENT BEFORE STUDY: NR

TITRATION PERIOD: NR

GLYCAEMIC TARGET:
Both groups: FBG ≤ 7.1mmol/L, postprandial blood glucose ≤ 11.1mmol/L, HbA1c ≤ 7.0%

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): biochemical variables

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 6 months

DURATION OF FOLLOW‐UP: 6 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: Chinese

NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote "To investigate the effect of glimepiride and metformin on free fatty acid in patients with Type 2 diabetes mellitus and to further study the relationship between free fatty acid and insulin resistance in patients with Type 2 diabetes mellitus." [From English abstract].

Notes

The abstract described the trial as a prospective case‐control study, where patients were divided into 3 groups. In the main text the author state that the patients were randomised.

Intervention group in trial, not included in the review: glimepiride plus metformin

The number of patients with previous cardiovascular disease is the number of patients with hypertension

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"....randomised..." [translated from Chinese]

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

We assume not blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

No loss to follow‐up reported

Selective reporting (reporting bias)

Unclear risk

No related information provided

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Low risk

"Sponsored by 15th National Research Project (2001BAA702B04); Science and Technology research Project of Hunan Province (03ssy3069)." [Translated from Chinese]

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Teramoto 2007

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Comparator: pioglitazone

Participants

INCLUSION CRITERIA:

  • Japanese

  • T2DM

  • 20 to 79 years old

  • received dietary and exercise instructions, without antidiabetic and hypolipidaemic agents

  • they had ≥ 140 mg/dl of FPG levels, ≤180 mg/dl of high‐density lipoprotein cholesterol levels and triglycerides levels between 150 mg/dl and 500 mg/dl

EXCLUSION CRITERIA:

  • taking medications known to influence glucose metabolism

  • history of ketoacidosis or with an unstable progressive diabetic coma or pre‐coma condition

  • impaired liver function, kidney function, abnormal lipid metabolism

  • allergy to thiazolidinediones and/or sulphonylurea

  • tumour therapy

  • alcohol abuse

  • myocardial infarction

  • cerebrovascular dysfunction

  • receiving insulin due to severe infection

DIAGNOSTIC CRITERIA:

NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Comparator: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR/NR/0

Comparator: NR/NR/0

Interventions

NUMBER OF STUDY CENTRES: 18

COUNTRY/LOCATION: Japan

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: 8 weeks

GLYCAEMIC TARGET: FPG < 126 mg/dl

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): biochemical variables

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 24 weeks

DURATION OF FOLLOW‐UP: 24 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING: NR

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "The effects of pioglitazone hydrochloride monotherapy on abnormal lipid control were evaluated in Japanese patients with type 2 diabetes mellitus, comparing with glibenclamide monotherapy."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "This study was a randomized..."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label

Blinding of outcome assessment (detection bias)
All outcomes

High risk

We assume not blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Not extensively described

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Unclear risk

NR

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Tessier 1999

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: gliclazide

Comparator: metformin

Participants

INCLUSION CRITERIA:

  • ambulatory patients

  • no acute cardiological or neurological events in the prior 6 months

  • no previous treatment with gliclazide, metformin, thiazide, beta‐blockers, steroids or insulin

EXCLUSION CRITERIA: described within the inclusion criteria

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: gliclazide

Control: metformin

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: Canada

SETTING: outpatients

TREATMENT BEFORE STUDY: not gliclazide, metformin or insulin; other oral were withdrawn 30 days prior to randomisation

TITRATION PERIOD: not reported, but the dose was gradually increased

GLYCAEMIC TARGET: self monitoring less than 8.0 mmol/L fasting in the morning, less than 10 mmol/L after meals

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): efficacy, lipid peroxidation and side effects

Study details

RUN‐IN PERIOD: 30 days

DURATION OF INTERVENTION: 24 weeks

DURATION OF FOLLOW‐UP: 24 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "Consequently, the goal of this study is to compare gliclazide and metformin in patients with type 2 diabetes mellitus with regard to efficacy, side effects profile, and lipid peroxidation."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Each subject were then randomized to…"

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Open‐label design

Incomplete outcome data (attrition bias)
All outcomes

Low risk

3 drop‐outs, reasons explained

Selective reporting (reporting bias)

Unclear risk

No design article or protocol available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical company

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Tosi 2003

Methods

CROSS‐OVER RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: metformin

Participants

INCLUSION CRITERIA:

  • T2DM

  • FPG greater than 140 mg/dl

  • HbA1c ≥ 6.3%

EXCLUSION CRITERIA:

  • insulin‐treated patients

  • ketonuria

  • concurrent medical illness

  • severe diabetic complications

  • severe cardiovascular, hepatic, renal, respiratory or pancreatic diseases

DIAGNOSTIC CRITERIA: ADA criteria

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: 0

Control: 0

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: 1/8/1

Control: 0/8/3

Interventions

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: Italy

SETTING: outpatients

TREATMENT BEFORE STUDY: diet and/or oral antidiabetic intervention

TITRATION PERIOD: 4 weeks

GLYCAEMIC TARGET: during both phases of the study, doses were titrated in 4 steps (at intervals of minimum 20 days) to achieve HbA1c ≤ 6.0% and fasting plasma glucose less than 140 mg/dL, in the absence of hypoglycaemic episodes

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, FBG, insulin resistance, BMI, lipids and side effects

Study details

RUN‐IN PERIOD: 4 weeks

DURATION OF INTERVENTION: 6 months, thereafter switch to combination therapy

DURATION OF FOLLOW‐UP: 6 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "In the present randomized, double‐blind trial, efficacy and tolerability of metformin and glibenclamide given alone or in combination were compared in 88 type 2 diabetic patients,using a cross‐over design."

Notes

The combination group of glibenclamide plus metformin is not included in the meta‐analysis

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "After a 4‐week run‐in period (T 0), eligible patients were randomized to 3 treatment groups…"

The random allocation schedule was generated by the pharmaceutical technique department (from correspondence)

Allocation concealment (selection bias)

Low risk

Quote: "All tablets were supplied by Guidotti Laboratories, Pisa, Italy, which generated the allocation schedule and provided the blinding procedure."

Each drug was prepared and labelled by sequential number according to the allocation schedule. Participants were assigned in numbers in a consecutive order by a physician, who was blinded to treatments (from correspondence)

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "All tablets were supplied by Guidotti Laboratories, Pisa, Italy, which generated the allocation schedule and provided the blinding procedure."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

We assume outcome assessors were adequately blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Difficult to assess drop‐outs and their reasons after the first intervention period

Selective reporting (reporting bias)

Low risk

Primary outcome very vaguely defined in publication, but clarified through communication with corresponding author

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical company

Trials according to risk of bias

Low risk

Adequate sequence generation, allocation concealment and blinding
UGDP 1970

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind evaluation of oral intervention, open‐label for insulin

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: tolbutamide

Control 1: placebo

Control 2: insulin

Participants

INCLUSION CRITERIA:

  • maturity onset diabetes diagnosed within 12 months prior to enrolment in the study (the time of diagnosis was determined by the date of the first glucose tolerance test or by the time which hypoglycaemic treatment had been first initiated)

  • free of life‐endangering diseases and a minimal life expectancy of 5 years at entry into the study in the clinicians' judgement

  • a diagnostic glucose tolerance test in which the sum of the 4 individual blood glucose values was ≥ 500 mg per 100 ml

  • free of ketoacidosis and other major diabetic symptoms on diet alone during a 4‐week observation period immediately preceding entry into the study

  • patient willing and able to participate in the study

EXCLUSION CRITERIA: prior history of ketoacidosis

DIAGNOSTIC CRITERIA: patients fulfilling the requirements got a diagnostic test. Diagnostic test: the sum of 4 glucose values from glucose tolerance test had to be equal or greater than 500 mg/100 ml in order to be eligible for the study)

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: 14

Control 1: 10

Control 2: 16

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: 4/55/NR

Control 1: 7/48/NR

Control 2: 7/62/NR

Interventions

NUMBER OF STUDY CENTRES: 12

COUNTRY/LOCATION: USA

SETTING: outpatients

TREATMENT BEFORE STUDY: hypoglycaemic therapy, not further specified

TITRATION PERIOD: NR

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): vascular complications, natural history of diabetes

Study details

RUN‐IN PERIOD: 4 weeks

DURATION OF INTERVENTION: 4.75 years

DURATION OF FOLLOW‐UP: 4.75 years

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "The University Group Diabetes Program had three major objectives: (1) Evaluation of the efficacy of various hypoglycaemic treatments in the prevention of vascular complications in patients with mild diabetes. (2) Study of the natural history of a group of patients with maturity onset, noninsulin dependent diabetes. (3) Development of methods applicable to cooperative clinical trials."

Notes

The phenformin group is not included in the analysis as it was included in the trial 18 months after the other interventions groups. The insulin variable (IVAR) intervention group had a more strict glycaemic target and is therefore not included in the analysis.

The insulin data is from the insulin standard intervention group in trial. Data from this intervention group are reported after a duration of intervention of 5.75 years to make the data comparable with tolbutamide.

The number reported with previously cardiovascular disease is the number of participants with angina

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Patients enrolled in the UGDP were randomly assigned to one of the five treatment groups. All assignments were made by the UGDP coordinating center."

Allocation concealment (selection bias)

Low risk

Quote: "Separate allocation schedules were used for each of the participating Clinical Centers. These schedules were prepared using a table of random numbers and were designed to insure a specified number of patients in each of the treatment groups in a given clinic at periodic intervals throughout the course of the recruitment. The allocation procedure used in each of these clinics was designed to provide the same number of patients in each of these four treatments groups after every sixteenth allocation. (Another assignment ratio when phenformin was added)."

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

The tolbutamide and placebo group is adequately blinded. Quote: "Lactose placebo was given in tablet form which was indistinguishable by inspection from tolbutamide. The dosage schedule chosen was the same as for tolbutamide."

The insulin group was open‐label

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "…blind evaluation long‐term observation of patients, and central collection, editing, and monitoring of the observed data."

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Not specifically described for each intervention group

Quote: "A total of 654 out of 823 patients had 5 complete years of follow‐up…"

Selective reporting (reporting bias)

Low risk

Outcomes predefined in design article and assessed

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Low risk

No pharmaceutical funding

Trials according to risk of bias

Unclear risk

Adequate sequence generation, allocation concealment and blinding of outcome assessors. Unclear blinding of participants and investigators

UKPDS 1998

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea 1: chlorpropamide

Sulphonylurea 2: glibenclamide

Sulphonylurea 3: glipizide

Control: insulin

Participants

INCLUSION CRITERIA:

  • newly diagnosed T2DM patients

  • aged 25 to 65 years inclusive

  • FPG greater than 6 mmol/L on 2 mornings, 1 to 3 weeks apart

EXCLUSION CRITERIA:

  • ketonuria > 3 mmol/L

  • history of myocardial infarction in the previous year

  • current angina or heart failure

  • more than 1 major vascular episode

  • serum creatinine > 175 µmol/L

  • severe retinopathy requiring photocoagulation

  • malignant hypertension

  • an uncorrected endocrine abnormality

  • an occupation which would not allow randomisation to insulin therapy (e.g. heavy goods vehicle driver)

  • severe concurrent illness likely to limit life (e.g. cancer) or requiring extensive systemic treatment (e.g. ulcerative colitis)

  • inadequate comprehension to allow co‐operation

DIAGNOSTIC CRITERIA: FPG > 6 mmol/L on 2 occasions

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea 1: 9/69/2

Sulphonylurea 2: 7/69/0

Sulphonylurea: NR/NR/NR

Control: insulin: 16/97/2

Interventions

NUMBER OF STUDY CENTRES: 23

COUNTRY/LOCATION: United Kingdom

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: the antidiabetic interventions were up titrated during the intervention period to achieve/maintain glycaemic target

GLYCAEMIC TARGET: the aim of intensive treatment was FPG less than 6 mmol/L and, in insulin‐treated patients, pre‐meal glucose concentrations of 4 to 7 mmol/L

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): any diabetes‐related outcome, diabetes‐related death, all‐cause mortality, single components of macrovascular and microvascular outcomes, surrogate clinical outcomes, hyperglycaemic, quality of life

Study details

RUN‐IN PERIOD: 3 months

DURATION OF INTERVENTION: 10.0 years

DURATION OF FOLLOW‐UP: 10.0 years

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "We compared the effects of intensive blood‐glucose control with either sulphonylurea or insulin and conventional treatment on the risk of microvascular and macrovascular complications in patients with type 2 diabetes in a randomised controlled trial."

Notes

The number of patients treated with aspirin/antihypertensives/lipid‐lowering are only for the participants in glucose study 1. The number for aspirin is the number taking more than one a day, the number for antihypertensives are other than diuretics.

We have not included data from the conventional intervention group in the UKPDS, as it had another glycaemic target.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Randomisation was by means of centrally produced, computer‐generated therapy allocations in sealed, opaque envelopes which were opened in sequence."

Allocation concealment (selection bias)

Low risk

Quote: "Randomisation was by means of centrally produced, computer‐generated therapy allocations in sealed, opaque envelopes which were opened in sequence."

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design: "The trial was open once patients were randomised"

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "Members of the UKPDS end‐point committee, who were unaware of assignments to study groups, adjudicated outcomes.."

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Loss to follow‐up for each of the antidiabetic drug groups is not clearly described

Selective reporting (reporting bias)

High risk

Quote: "A subsidiary comparison is between those allocated to insulin and those allocated to sulphonylurea in all the randomisation groups to assess whether either has a specific risk or advantage."

Not all the participants randomised in the sulphonylurea group are reported in the major comparison, as the primary and secondary outcomes for the participants randomised to glipizide and chlorpropamide in the Glucose II trial are not reported

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical company

Trials according to risk of bias

Unclear risk

Adequate sequence generation and allocation concealment, inadequate blinding of participants and investigators

UKPDS 34 1998

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea 1: chlorpropamide

Sulphonylurea 2: glibenclamide

Control 1: metformin

Control 2: insulin

Participants

INCLUSION CRITERIA:

  • newly diagnosed T2DM patients

  • aged 25 to 65 years inclusive

  • FPG greater than 6 mmol/L on 2 mornings, 1 to 3 weeks apart

  • > 120% of ideal bodyweight

EXCLUSION CRITERIA:

  • ketonuria > 3 mmol/L

  • history of myocardial infarction in the previous year

  • current angina or heart failure

  • more than 1 major vascular episode

  • serum creatinine > 175 µmol/L

  • severe retinopathy requiring photocoagulation

  • malignant hypertension

  • an uncorrected endocrine abnormality

  • an occupation which would not allow randomisation to insulin therapy (e.g. heavy goods vehicle driver)

  • severe concurrent illness likely to limit life (e.g. cancer) or requiring extensive systemic treatment (e.g. ulcerative colitis)

  • inadequate comprehension to allow co‐operation

DIAGNOSTIC CRITERIA: fasting plasma glucose > 6 mmol/L on 2 occasions

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea 1: NR

Sulphonylurea 2: NR

Control 1: NR

Control 2: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea 1: 5/40/2

Sulphonylurea 2: 3/44/2

Control 1: 5/51/1

Control 2: 12/49/1

Interventions

NUMBER OF STUDY CENTRES: 15

COUNTRY/LOCATION: United Kingdom

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: the antidiabetic interventions were up titrated during the intervention period to achieve/maintain glycaemic target

GLYCAEMIC TARGET: the aim of intensive treatment was FPG less than 6 mmol/L and, in insulin‐treated patients, pre‐meal glucose concentrations of 4 to 7 mmol/L

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): any diabetes‐related outcome, diabetes‐related death, all‐cause mortality, single components of macrovascular and microvascular outcomes, surrogate clinical outcomes, hyperglycaemic, quality of life

Study details

RUN‐IN PERIOD: 3 months

DURATION OF INTERVENTION: 10.7 years

DURATION OF FOLLOW‐UP: 10.7 years

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "This study investigated whether intensive glucose control with metformin has any specific advantage or disadvantage."

Notes

The number for aspirin is the number taken more than one a day, the number for antihypertensives are other than diuretics.

We have not included data from the conventional intervention group in the UKPDS, as it had another glycaemic target

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

We assume the same method was applied as in UKPDS 1998

Allocation concealment (selection bias)

Low risk

Quote: "....allocations in sealed, opaque envelopes which were opened in sequence."

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

We assume the same method was applied as in UKPDS 1998

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Loss to follow‐up for each of the antidiabetic drug groups is not clearly described

Selective reporting (reporting bias)

High risk

Quote: "The response to metformin therapy in the obese subjects is assessed by comparison with those allocated to diet policy and to sulphonylurea therapy." However, this comparison has never been reported.

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received funding from pharmaceutical company

Trials according to risk of bias

Unclear risk

Adequate sequence generation, allocation concealment and blinding of outcome assessors, inadequate blinding of participants and investigators

van de Laar 2004

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: tolbutamide

Control: acarbose

Participants

INCLUSION CRITERIA:

  • participants either with symptoms suggestive of diabetes mellitus and a capillary FBG ≥ 6.7 mmol/L or patients in whom a raised blood glucose level was found coincidentally

  • for patients without symptoms more than 1 abnormal fasting blood glucose was needed

  • patients were eligible for the trial if their FBG levels were between 6.7 and 20.0 mmol/L after an 8‐week dietary treatment period (see below), and they met the following criteria: age between 40 and 70 years

  • sufficient understanding of spoken Dutch to follow instructions

EXCLUSION CRITERIA:

  • any significant disease or condition likely to prevent patients from completing the study

  • uncorrected endocrine disturbances

  • pregnancy or breast‐feeding

  • women of childbearing age not using contraceptives

  • diseases with abnormal gut motility or altered absorption of nutrients or use of medications for such conditions

  • use of systemic glucocorticoids

  • hypersensitivity or other contraindications to acarbose or tolbutamide

  • habitual use of drugs or an alcohol intake > 10 units daily

  • lactose intolerance

  • participation in another experimental study

  • serum cholesterol > 10 mmol/L or a serum triglyceride > 4 mmol/L

  • use of lipid‐lowering agents containing ionic‐substitution resins (e.g. colestipol)

  • aspartate aminotransferase > 50 U/L, alanine aminotransferase > 50 U/L, gamma glutamyltransferase > 150 U/L

  • creatinine > 150 µmol/L

  • myocardial infarction within the last 6 months

DIAGNOSTIC CRITERIA:

Symptoms suggestive of diabetes mellitus and a capillary FBG ≥ 6.7 mmol/L or patients in whom a raised blood glucose level was found coincidentally

For patients without symptoms more than 1 abnormal fasting blood glucose was needed

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR/11/3

Control: NR/3/4

Interventions

NUMBER OF STUDY CENTRES: 46

COUNTRY/LOCATION: The Netherlands

SETTING: outpatients, general practice

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: 6 weeks

GLYCAEMIC TARGET: FBG less than 6.7 mmol/L

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, fasting and post‐load blood glucose and insulin levels, lipids and adverse events

Study details

RUN‐IN PERIOD: 8 weeks

DURATION OF INTERVENTION: 30 weeks

DURATION OF FOLLOW‐UP: 30 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "We performed a double blind randomised controlled trial in general practice to assess equivalence between tolbutamide and acarbose with respect to the effect on mean HbA1c in newly diagnosed patients with type 2 diabetes."

Notes

Number of patients on antihypertensive is the number receiving agent acting on the renin‐angiotensin system

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "We performed a double blind randomised controlled trial in general practice to assess equivalence between tolbutamide and acarbose with respect to the effect on mean HbA1c in newly diagnosed patients with type 2 diabetes."

Allocation concealment (selection bias)

Low risk

Quote: "The clinical quality assurance manager kept the allocation schedule in a central study file not accessible to the participating general practitioners. The code was sent to the general practitioner in a sealed radio‐opaque envelope that was only to be broken in case of a medical emergency. At the end of the study the envelope had to be returned unopened."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "Because of the different sizes of the actual tablets it was necessary to use the so‐called ‘double dummy’ technique to ensure blinding. All patients received two sets of pills, apparently acarbose and tolbutamide, but only one set contained an active substance."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

We assume the outcome assessors were blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All loss to follow‐up described

Selective reporting (reporting bias)

Low risk

All primary and secondary outcomes reported

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Sponsored by pharmaceutical company

Trials according to risk of bias

Low risk

Adequate sequence generation, allocation concealment and blinding
Watanabe 2005

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: not described, we assume open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: pioglitazone

Participants

INCLUSION CRITERIA:

  • T2DM

  • HbA1c between 6.5% and 8.0%

  • naive to antidiabetic drugs

EXCLUSION CRITERIA:

  • kidney disease

DIAGNOSTIC CRITERIA: FPG > 126 mg/dL

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR/11/13

Control: NR/8/14

Interventions

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: Japan

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: NR

GLYCAEMIC TARGET: decrease of plasma glucose level equivalent to a decline of 0.6% in terms of HbA1c in 6 months

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): change in pulse‐wave velocity, BMI, blood pressure, brachial‐ankle pulse‐wave velocity, FPG, HbA1c, fasting immunoreactive insulin, homeostasis model insulin resistance index, total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol and triglyceride

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 6 months

DURATION OF FOLLOW‐UP: 6 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING: NR

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "To investigate the anti‐arteriosclerotic effects of pioglitazone in patients with diabetes mellitus using pulse wave velocity (PWV) as an index of efficacy"

Notes

Number of patients with antihypertensives reported are only ACE‐inhibitors

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "They were randomly divided into two groups..."

Allocation concealment (selection bias)

Low risk

Quote: "They were randomly divided into two groups by the envelope method (when the patient was registered, we opened the envelope in which contained either a card printed for pioglitazone (PIO) or for glibenclamide (GC) and followed the instructions), and assigned to receive either PIO or GC."

Blinding of participants and personnel (performance bias)
All outcomes

High risk

We assume open‐label, no blinding described

Blinding of outcome assessment (detection bias)
All outcomes

High risk

We assume open‐label, no blinding described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Quote: "In the PIO group, drug administration was discontinued in two patients because of the development of edema. In the GC group, drug administration was discontinued in one patient because of signs of hypoglycemia. Therefore, a total of three patients were excluded from the present study."

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Unclear risk

Funding not reported

Trials according to risk of bias

Unclear risk

Unclear sequence generation, adequate allocation concealment, inadequate blinding
Wolffenbuttel 1989

Methods

CROSS‐OVER RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: tolbutamide

Control: insulin

Participants

INCLUSION CRITERIA:

  • T2DM

  • non‐obese

  • islet‐cell negative antibodies

  • no ketonuria

  • no family history of type 1 diabetes

  • FBG > 8 mmol/L

  • stable body weight and blood glucose control after run‐in period

EXCLUSION CRITERIA:

  • impaired kidney function

  • severe hypertension

  • elevated liver enzymes

  • intervention with corticosteroids

DIAGNOSTIC CRITERIA: WHO

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Control: NR

Interventions

NUMBER OF STUDY CENTRES: 1

COUNTRY/LOCATION: The Netherlands

SETTING: outpatients

TREATMENT BEFORE STUDY: diet or exercise

TITRATION PERIOD: NR

GLYCAEMIC TARGET: FBG < 8.0 mmol/L, HbA1c < 9%

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): glycaemic control, beta‐cell function and lipids

Study details

RUN‐IN PERIOD: 3 months

DURATION OF INTERVENTION: 6 months

DURATION OF FOLLOW‐UP: 6 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "In 13 non‐obese patients with Type 2 diabetes mellitus who failed to achieve adequate blood glucose control on dietary treatment (fasting blood glucose 13.4 +/‐ 2.7 (+/‐ SD) mmol l‐1, glycosylated haemoglobin 13.0 +/‐ 1.7%), the effects of 6 months insulin or sulphonylurea therapy on blood glucose control and lipid metabolism were compared in a randomized crossover study."

Notes

Group of healthy controls not included in the analyses

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Patients were randomly assigned to start either therapy."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

We assume not blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Loss to follow‐up not adequately described

Selective reporting (reporting bias)

Unclear risk

No protocol or design article

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Received grant from industry

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding
Wolffenbuttel 1999

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: double‐blind

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glibenclamide

Control: repaglinide

Participants

INCLUSION CRITERIA:

  • T2DM

  • oral blood glucose–lowering agents and/or diet

  • age 40 to 75 years

  • BMI of 21.0 to 35.0 kg/m2

  • HbA1c > 6.5% when treated with diet only and < 12% when treated with diet plus oral blood glucose–lowering agents

EXCLUSION CRITERIA:

  • abnormal kidney or liver function (elevated serum creatinine > 140 µmol/L, elevated

  • transaminases more than 2 times the upper limit of normal)

  • a medical history of chronic insulin treatment

  • active cardiac problems (i.e. congestive heart failure)

  • unstable angina pectoris

  • recent myocardial infarction

  • severe uncontrolled hypertension (systolic blood pressure > 200 mmHg and/or diastolic blood pressure > 110 mmHg) either untreated or while on antihypertensive treatment; any other disease that could interfere with study participation or outcome were excluded from the study

  • contraindications to sulphonylureas

  • pregnant

  • breast‐feeding

  • intended to become pregnant

  • systemic treatment with corticosteroids

DIAGNOSTIC CRITERIA: WHO

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Comparator: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR

Comparator: NR

Interventions

NUMBER OF STUDY CENTRES: 42

COUNTRY/LOCATION: The Netherlands, Germany and Austria

SETTING: outpatients

TREATMENT BEFORE STUDY: diet and/or oral antidiabetic drugs

TITRATION PERIOD: 6 to 8 weeks

GLYCAEMIC TARGET:

Targets for treatment were fasting blood glucose of 4.4 to 6.1 mmol/L and postprandial levels of 4.4 to 8.0 mmol/L and HbA1c < 6.5%

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): glycaemic values, insulin, lipids, hypoglycaemia and adverse events

Study details

RUN‐IN PERIOD: 1 week

DURATION OF INTERVENTION: 12 months + 6 to 8 weeks

DURATION OF FOLLOW‐UP: 12 months + 6 to 8 weeks

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "This multicenter study was designed to compare the efficacy and safety of this drug with glyburide in a 1‐year randomized double‐blind study of outpatients with type 2 diabetes."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "The patients visited the outpatient clinic 1 week later and were asymmetrically randomized into blocks of six patients per treatment group in a 2:1 ratio of repaglinide to glyburide."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "To maintain the thrice‐daily dosing regimen, the glyburide group received placebo tablets at meals where no glyburide was taken."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

As the trial is double‐blinded and we assume the doctor assessed the outcome, we judged blinding as outcome assessors as low risk of bias

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss to follow‐up not adequately described

Selective reporting (reporting bias)

Low risk

Primary and secondary outcomes assessed as predefined

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

High risk

Sponsored by pharmaceutical company

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, adequate blinding
Yamanouchi 2005

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: NR, we assume open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glimepiride

Control 1: pioglitazone

Control 2: metformin

Participants

INCLUSION CRITERIA:

  • T2DM

  • never used antidiabetic drugs

  • HbA1c ≥ 7.0% and FPG ≥ 7.78 mmol/L at the end of the 1‐month observation period

EXCLUSION CRITERIA:

  • unstable or rapidly progressive diabetic retinopathy, nephropathy or neuropathy

  • liver dysfunction (aspartate aminotransferase (AST), alanine aminotransferase (ALT) > 1.5 upper limit of normal)

  • impaired kidney function (serum creatinine > 133 µmol/L)

  • anaemia

  • myocardial infarction

  • angina

  • congestive heart failure

  • cerebrovascular accident

DIAGNOSTIC CRITERIA: NR

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: NR

Control 1: NR

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVES/LIPID‐LOWERING:

Sulphonylurea: NR/18/0

Control 1: NR/16/0

Control 2: NR/18/0

Interventions

NUMBER OF STUDY CENTRES: NR

COUNTRY/LOCATION: Japan

SETTING: outpatients

TREATMENT BEFORE STUDY: diet

TITRATION PERIOD: NR

GLYCAEMIC TARGET: HbA1c ≤ 7%

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): HbA1c, metabolic variables

Study details

RUN‐IN PERIOD: 1 month

DURATION OF INTERVENTION: 12 months

DURATION OF FOLLOW‐UP: 12 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: English

COMMERCIAL FUNDING/NON‐COMMERCIAL FUNDING: NR

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote: "To compare the metabolic effects of pioglitazone, metformin, and glimepiride in the treatment of Japanese patients with newly diagnosed Type 2 diabetes."

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Random assignment was determined by the biostatistician, who provided sealed sequentially numbered envelopes opened only at the time of randomization."

Allocation concealment (selection bias)

Low risk

Quote: "Random assignment was determined by the biostatistician, who provided sealed sequentially numbered envelopes opened only at the time of randomization."

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Blinding not described, we assume open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Blinding not described, we assume open‐label design

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All loss to follow‐up sufficiently described

Selective reporting (reporting bias)

Unclear risk

No trial protocol or design article available

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Unclear risk

Funding not reported

Trials according to risk of bias

Unclear risk

Adequate sequence generation and allocation concealment, inadequate blinding
Zhang 2005

Methods

PARALLEL RANDOMISED CONTROLLED CLINICAL TRIAL

DOUBLE‐BLIND/OPEN‐LABEL: open‐label

INTERVENTIONS USED IN TRIALS:

Sulphonylurea: glipizide

Comparator: rosiglitazone

Participants

INCLUSION CRITERIA:

  • initial diagnosis of T2DM

  • male patients older than 65 years

  • all signed the informed consent

EXCLUSION CRITERIA:

  • refused to participate

  • received hypoglycaemic treatment before participating in the trial

  • history of hypertension and coronary heart disease

  • taking lipid‐lowering drugs during the trial or liver and kidney dysfunction before treatment

DIAGNOSTIC CRITERIA: WHO criteria 1999

NUMBER OF PATIENTS WITH PREVIOUS CARDIOVASCULAR DISEASE:

Sulphonylurea: 0

Comparator: 0

NUMBER OF PATIENTS TREATED WITH ASPIRIN/ANTIHYPERTENSIVE/LIPID‐LOWERING:

Sulphonylurea: NR

Comparator: NR

Interventions

NUMBER OF STUDY CENTRES: 24

COUNTRY/LOCATION: China

SETTING: outpatients

TREATMENT BEFORE STUDY: treatment‐naive

TITRATION PERIOD: NR

GLYCAEMIC TARGET: NR

Outcomes

OUTCOME(S) (as stated in the protocol/registered trial documents): biochemical variables, carotis intima‐media thickness

Study details

RUN‐IN PERIOD: NR

DURATION OF INTERVENTION: 6 months

DURATION OF FOLLOW‐UP: 6 months

STUDY TERMINATED BEFORE REGULAR END: no

Publication details

LANGUAGE OF PUBLICATION: Chinese

NON‐COMMERCIAL FUNDING

PUBLICATION STATUS: peer‐reviewed journal

Stated aim of study

Quote "To study the effects of thiazolidinediones (TZDs) on anti‐atherosclerosis in elder male patients with type 2 diabetes, and understand related factors induced this function."

Notes

The 2 rosiglitazone groups are meta‐analysed as 1 group

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Quote: "Randomly allocated into 3 groups."

Allocation concealment (selection bias)

Unclear risk

NR

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label design

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Outcome assessors not blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

"All of the included patients completed 6 months’ follow‐up."

Selective reporting (reporting bias)

Unclear risk

Not clearly stated

Academic bias

Low risk

Primary author's first publication on the interventions

Sponsor bias

Low risk

Quote: "This trial was supported by Chinese Medical Care Centre Foundation, No. HeiB055."

Trials according to risk of bias

Unclear risk

Unclear sequence generation and allocation concealment, inadequate blinding

ACE: angiotension converting enzyme; ADA: American Diabetes Association; ADOPT: A Diabetes Outcome Progression Trial; (cyclic) AMP: adenosine monophosphate;APPROACH: Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in Type 2 Diabetes Patients with Cardiovascular History; BMI: body mass index; FBG: fasting blood glucose; FPG: fasting plasma glucose; HbA1c: glycosylated haemoglobin A1c; LEAD‐3: Liraglutide Effect and Action in Diabetes‐3; NR: not reported; NYHA: New York Heart Association; PPG: postprandial plasma glucose; T2DM: type 2 diabetes mellitus; UKPDS: United Kingdom Prospective Diabetes Study; WHO: World Health Organization

Characteristics of excluded studies [ordered by study ID]

Ir a:

Study

Reason for exclusion

Adetuyibi 1977

Duration of intervention less than 24 weeks

Adlung 1974

Not a randomised clinical trial

Ahuja 1973

Not a randomised clinical trial.

Akanuma 1988

Not comparing interventions of interest. Comparing gliclazide with a mixed group of sulphonylureas. Participants in diet group are not randomised.

Almer 1984

Not a randomised clinical trial

Aman 1977

Not a randomised clinical trial

Baba 1983

Not comparing interventions of interest. Comparing glimepiride with glibenclamide.

Balabolkin 1983

Not a randomised clinical trial

Balabolkin 1988

Not a randomised clinical trial

Banerji 1995

Not including patients with T2DM

BARI 2009

Not comparing interventions of interest. Patients are randomised to insulin provision regime (not only sulphonylureas).

Bellomo 2011

Duration of intervention less than 24 weeks

Belovalova 1990

Not a randomised clinical trial

Ben 1988

Not a randomised clinical trial

Berber 1982

Duration of intervention less than 24 weeks

Bernas 1992

Not a randomised clinical trial

Berry 1981

Not a randomised clinical trial

Blumenbach 1976

Not a randomised clinical trial

Bruns 1990

Duration of intervention less than 24 weeks

Calvagno 1983

Not a randomised clinical trial

Cefalu 1998

Duration of intervention less than 24 weeks

Ceriello 2005

Not a randomised clinical trial

Chan 1982

Not comparing interventions of interest. Comparing gliclazide with glibenclamide.

Chandra 2008

Not a randomised clinical trial. Authors asked and replied.

Chen 1987

Not a randomised clinical trial

Cortinovis 1998

Not a randomised clinical trial

Derosa 2010

Not comparing the interventions of interest. Metformin is continued after the randomisation.

Dills 1996

Not comparing interventions of interest. Comparing glimepiride with glibenclamide.

Dowey 1979

Not a randomised clinical trial

Drouin 2000

Not comparing interventions of interest. Comparing 2 different formulas of gliclazide.

Drouin 2004

Not comparing interventions of interest. Comparing 2 different formulas of gliclazide.

Duprey 1971

Not a randomised clinical trial

Engelhardt 1965

Includes also patients with normal glucose tolerance

Ferner 1991

Not a randomised clinical trial

Forst 2011

Not a randomised clinical trial

Fuchs 1973

Duration of intervention in publication less than 24 weeks. Report that data after 1 year of intervention will be published, but publication could not be found. Attempt made to contact authors.

Garber 2002

Duration of intervention less than 24 weeks

Garber 2003

Duration of intervention less than 24 weeks

Gargiolo 2001

Not a randomised clinical trial

Giles 2008

Not comparing the interventions of interest. Patients are not exclusively allocated to sulphonylurea monotherapy, but some of the patients receive insulin in combination with sulphonylurea.

Giles 2010

Not comparing the interventions of interest. Metformin is continued after the randomisation.

Goldberg 1996

Duration of intervention less than 24 weeks

Groop 1989

Not comparing the interventions of interest

Gudat 1998

Not a randomised clinical trial

Gurling 1970

Not a randomised clinical trial

Happ 1974

Duration of intervention less than 24 weeks

Haupt 1974

Not a randomised clinical trial

Hollander 2001

Duration of intervention less than 24 weeks

Howes 2000

Not a randomised clinical trial

Hristov 2002

Not a randomised clinical trial

Hussain 2007

Not comparing the interventions of interest. The 3 randomised groups receive glibenclamide.

Inukai 2005

Not comparing the interventions of interest. Comparing glimepiride with glibenclamide/gliclazide.

Irsigler 1979

Duration of intervention less than 24 weeks

Ishizuka 1994

Not a randomised clinical trial

Jackson 1969

Not a randomised clinical trial

Jerums 1987

Not comparing interventions of interest. The randomised groups receive gliclazide and glibenclamide.

Johnston 1970

Duration of intervention less than 24 weeks

Josephkutty 1990

Duration of intervention less than 24 weeks

Joshi 2002

Duration of intervention less than 24 weeks

Kakhnovskii 1993

Not a randomised clinical trial

Kanoun 1996

Not a randomised clinical trial

Langenfeld 2005

Not comparing the interventions of interest. Metformin is continued after the randomisation.

Lecomte 1977

Duration of intervention less than 24 weeks

Levy 1995

Duration of intervention less than 24 weeks

Li 2009

Not comparing the interventions of interest. The group randomised to insulin secretagogues receives both sulphonylurea and repaglinide.

Lim 1970

Duration of intervention less than 24 weeks

Lindbjerg 1976

Duration of intervention less than 24 weeks

Liu 1985

Duration of intervention less than 24 weeks

Lomuscio 1994

Not a randomised clinical trial

Mafauzy 2002

Duration of intervention less than 24 weeks

Mazzone 2006

Not comparing the interventions of interest. Metformin is continued after the randomisation. Correspondence with author.

Meneilly 2011

Duration of intervention less than 24 weeks

Mogensen 1976

Not comparing the interventions of interest. Comparing glibornuride with glibenclamide.

Nakamura 2000

Duration of intervention less than 24 weeks

Nikkilä 1982

Not comparing the interventions of interest. Comparing glibenclamide with gliquidone.

Nissen 2008

Not comparing the interventions of interest. Metformin is continued after the randomisation. Clarified after e‐mailing with corresponding author.

Noury 1991

Duration of intervention less than 24 weeks

Omrani 2005

Only published as abstract, and the patients described as divided. Attempt to contact primary author. We assume not a randomised clinical trial.

Osei 2003

Not including patients with type 2 diabetes mellitus

Papa 2006

Duration of intervention less than 24 weeks for each randomised group in the cross‐over trial

Perez 2006

Not comparing the interventions of interest. Metformin is continued after the randomisation.

Quatraro 1990

Not randomising participants to the intervention of interest, but only randomising patients to placebo or hydroxychloroquine in addition to glibenclamide.

Rao 2010

Not comparing the interventions of interest. Metformin is continued after the randomisation.

RECORD

Not comparing the interventions of interest. Investigates the effect of combination therapy.

Rosenstock 1993

Not comparing the interventions of interest. Comparing glibenclamide with glipizide.

Rupprecht 1993

Not a randomised clinical trial

Saadatnia 2009

Not a randomised clinical trial

Sami 1996

Not comparing the interventions of interest. Comparing glibenclamide with glipizide.

Sasahara 1999

Not a randomised clinical trial

Schernthaner 2004

Not comparing the interventions of interest. Metformin and alpha‐glucose inhibitors are continued after the randomisation.

Seck 2010

Not comparing the interventions of interest. Metformin is continued after the randomisation.

Shinoda 2009

Only published as abstract, and the patients described as divided. Attempt to contact primary author. We assume not a randomised clinical trial.

Speiser 1989

Duration of intervention less than 24 weeks

Tolman 2009

Not comparing the interventions of interest. Metformin is continued after the randomisation.

Tovi 1998

Not comparing interventions of interest. Other antidiabetic intervention is not stopped at entry to trial.

Toyota 1997

Duration of intervention less than 24 weeks

Tsumura 1995

Not comparing the interventions of interest. Comparing glimepiride with gliclazide.

Umpierrez 1997

Not exclusively including patients with T2DM

Vray 1995

Duration of intervention less than 24 weeks

Wang 1994

Duration of intervention less than 24 weeks

Wu 2010

Duration of intervention less than 24 weeks

Yang 2009

Not including patients with T2DM

Zhou 1999

Duration of intervention less than 24 weeks

T2DM: type 2 diabetes mellitus

Data and analyses

Open in table viewer
Comparison 1. Sulphonylureas versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

5

883

Risk Ratio (M‐H, Random, 95% CI)

1.51 [0.91, 2.52]
Analysis 1.1
Comparison 1 Sulphonylureas versus placebo, Outcome 1 All‐cause mortality.

Comparison 1 Sulphonylureas versus placebo, Outcome 1 All‐cause mortality.

1.1 First‐generation SU

2

553

Risk Ratio (M‐H, Random, 95% CI)

1.46 [0.87, 2.45]

1.2 Second‐generation SU

3

330

Risk Ratio (M‐H, Random, 95% CI)

4.86 [0.24, 99.94]

1.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 All‐cause mortality; best‐worst case scenario Show forest plot

1

57

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 1.2
Comparison 1 Sulphonylureas versus placebo, Outcome 2 All‐cause mortality; best‐worst case scenario.

Comparison 1 Sulphonylureas versus placebo, Outcome 2 All‐cause mortality; best‐worst case scenario.

2.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 Second‐generation SU

1

57

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 All‐cause mortality; worst‐best case scenario Show forest plot

1

57

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 1.3
Comparison 1 Sulphonylureas versus placebo, Outcome 3 All‐cause mortality; worst‐best case scenario.

Comparison 1 Sulphonylureas versus placebo, Outcome 3 All‐cause mortality; worst‐best case scenario.

3.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.2 Second‐generation SU

1

57

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4 Cardiovascular mortality Show forest plot

5

883

Risk Ratio (M‐H, Random, 95% CI)

2.64 [1.35, 5.17]
Analysis 1.4
Comparison 1 Sulphonylureas versus placebo, Outcome 4 Cardiovascular mortality.

Comparison 1 Sulphonylureas versus placebo, Outcome 4 Cardiovascular mortality.

4.1 First‐generation SU

2

553

Risk Ratio (M‐H, Random, 95% CI)

2.63 [1.32, 5.22]

4.2 Second‐generation SU

3

330

Risk Ratio (M‐H, Random, 95% CI)

2.91 [0.12, 70.71]

4.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Non‐fatal macrovascular outcomes Show forest plot

1

205

Risk Ratio (M‐H, Random, 95% CI)

1.32 [0.82, 2.13]
Analysis 1.5
Comparison 1 Sulphonylureas versus placebo, Outcome 5 Non‐fatal macrovascular outcomes.

Comparison 1 Sulphonylureas versus placebo, Outcome 5 Non‐fatal macrovascular outcomes.

5.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5.2 Second‐generation SU

1

205

Risk Ratio (M‐H, Random, 95% CI)

1.32 [0.82, 2.13]

5.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Non‐fatal myocardial infarction Show forest plot

1

409

Risk Ratio (M‐H, Random, 95% CI)

0.80 [0.43, 1.51]
Analysis 1.6
Comparison 1 Sulphonylureas versus placebo, Outcome 6 Non‐fatal myocardial infarction.

Comparison 1 Sulphonylureas versus placebo, Outcome 6 Non‐fatal myocardial infarction.

6.1 First‐generation SU

1

409

Risk Ratio (M‐H, Random, 95% CI)

0.80 [0.43, 1.51]

6.2 Second‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7 Amputation of lower extremity Show forest plot

1

409

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.01, 4.16]
Analysis 1.7
Comparison 1 Sulphonylureas versus placebo, Outcome 7 Amputation of lower extremity.

Comparison 1 Sulphonylureas versus placebo, Outcome 7 Amputation of lower extremity.

7.1 First‐generation SU

1

409

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.01, 4.16]

7.2 Second‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 Nephropathy Show forest plot

1

409

Risk Ratio (M‐H, Random, 95% CI)

1.26 [0.34, 4.61]
Analysis 1.8
Comparison 1 Sulphonylureas versus placebo, Outcome 8 Nephropathy.

Comparison 1 Sulphonylureas versus placebo, Outcome 8 Nephropathy.

8.1 First‐generation SU

1

409

Risk Ratio (M‐H, Random, 95% CI)

1.26 [0.34, 4.61]

8.2 Second‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9 Retinopathy Show forest plot

1

409

Risk Ratio (M‐H, Random, 95% CI)

0.93 [0.67, 1.30]
Analysis 1.9
Comparison 1 Sulphonylureas versus placebo, Outcome 9 Retinopathy.

Comparison 1 Sulphonylureas versus placebo, Outcome 9 Retinopathy.

9.1 First‐generation SU

1

409

Risk Ratio (M‐H, Random, 95% CI)

0.93 [0.67, 1.30]

9.2 Second‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10 Change in fasting blood glucose from baseline (mmol/L) Show forest plot

6

342

Mean Difference (IV, Random, 95% CI)

‐1.35 [‐2.00, ‐0.69]
Analysis 1.10
Comparison 1 Sulphonylureas versus placebo, Outcome 10 Change in fasting blood glucose from baseline (mmol/L).

Comparison 1 Sulphonylureas versus placebo, Outcome 10 Change in fasting blood glucose from baseline (mmol/L).

10.1 First‐generation SU

1

128

Mean Difference (IV, Random, 95% CI)

‐2.1 [‐3.19, ‐1.01]

10.2 Second‐generation SU

5

214

Mean Difference (IV, Random, 95% CI)

‐1.20 [‐1.94, ‐0.46]

10.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

11 Change in HbA1c from baseline (%) Show forest plot

6

342

Mean Difference (IV, Random, 95% CI)

1.00 [‐1.21, ‐0.79]
Analysis 1.11
Comparison 1 Sulphonylureas versus placebo, Outcome 11 Change in HbA1c from baseline (%).

Comparison 1 Sulphonylureas versus placebo, Outcome 11 Change in HbA1c from baseline (%).

11.1 First‐generation SU

1

128

Mean Difference (IV, Random, 95% CI)

‐0.94 [‐1.29, ‐0.59]

11.2 Second‐generation SU

5

214

Mean Difference (IV, Random, 95% CI)

‐1.02 [‐1.32, ‐0.72]

11.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

12 Change in BMI from baseline (kg/m2) Show forest plot

3

141

Mean Difference (IV, Random, 95% CI)

‐0.09 [‐0.59, 0.41]
Analysis 1.12
Comparison 1 Sulphonylureas versus placebo, Outcome 12 Change in BMI from baseline (kg/m2).

Comparison 1 Sulphonylureas versus placebo, Outcome 12 Change in BMI from baseline (kg/m2).

12.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

12.2 Second‐generation SU

3

141

Mean Difference (IV, Random, 95% CI)

‐0.09 [‐0.59, 0.41]

12.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

13 Change in weight from baseline (kg) Show forest plot

1

128

Mean Difference (IV, Random, 95% CI)

‐0.40 [‐1.36, 0.56]
Analysis 1.13
Comparison 1 Sulphonylureas versus placebo, Outcome 13 Change in weight from baseline (kg).

Comparison 1 Sulphonylureas versus placebo, Outcome 13 Change in weight from baseline (kg).

13.1 First‐generation SU

1

128

Mean Difference (IV, Random, 95% CI)

‐0.40 [‐1.36, 0.56]

13.2 Second‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

13.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

14 Adverse events Show forest plot

3

346

Risk Ratio (M‐H, Random, 95% CI)

1.23 [0.92, 1.64]
Analysis 1.14
Comparison 1 Sulphonylureas versus placebo, Outcome 14 Adverse events.

Comparison 1 Sulphonylureas versus placebo, Outcome 14 Adverse events.

14.1 First‐generation SU

1

144

Risk Ratio (M‐H, Random, 95% CI)

1.35 [0.97, 1.88]

14.2 Second‐generation SU

2

202

Risk Ratio (M‐H, Random, 95% CI)

0.91 [0.51, 1.62]

14.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

15 Drop‐outs due to adverse events Show forest plot

6

654

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.33, 1.36]
Analysis 1.15
Comparison 1 Sulphonylureas versus placebo, Outcome 15 Drop‐outs due to adverse events.

Comparison 1 Sulphonylureas versus placebo, Outcome 15 Drop‐outs due to adverse events.

15.1 First‐generation SU

1

144

Risk Ratio (M‐H, Random, 95% CI)

0.75 [0.17, 3.23]

15.2 Second‐generation SU

5

510

Risk Ratio (M‐H, Random, 95% CI)

0.62 [0.24, 1.57]

15.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

16 Mild hypoglycaemia Show forest plot

1

134

Risk Ratio (M‐H, Random, 95% CI)

12.26 [0.70, 213.33]
Analysis 1.16
Comparison 1 Sulphonylureas versus placebo, Outcome 16 Mild hypoglycaemia.

Comparison 1 Sulphonylureas versus placebo, Outcome 16 Mild hypoglycaemia.

16.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

16.2 Second‐generation SU

1

134

Risk Ratio (M‐H, Random, 95% CI)

12.26 [0.70, 213.33]

16.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

17 Severe hypoglycaemia Show forest plot

1

46

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 1.17
Comparison 1 Sulphonylureas versus placebo, Outcome 17 Severe hypoglycaemia.

Comparison 1 Sulphonylureas versus placebo, Outcome 17 Severe hypoglycaemia.

17.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

17.2 Second‐generation SU

1

46

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

17.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

18 Cancer Show forest plot

2

614

Risk Ratio (M‐H, Random, 95% CI)

0.54 [0.06, 5.05]
Analysis 1.18
Comparison 1 Sulphonylureas versus placebo, Outcome 18 Cancer.

Comparison 1 Sulphonylureas versus placebo, Outcome 18 Cancer.

18.1 First‐generation SU

1

409

Risk Ratio (M‐H, Random, 95% CI)

0.25 [0.07, 0.88]

18.2 Second‐generation SU

1

205

Risk Ratio (M‐H, Random, 95% CI)

2.91 [0.12, 70.71]

18.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19 Intervention failure Show forest plot

4

794

Risk Ratio (M‐H, Random, 95% CI)

0.26 [0.07, 0.94]
Analysis 1.19
Comparison 1 Sulphonylureas versus placebo, Outcome 19 Intervention failure.

Comparison 1 Sulphonylureas versus placebo, Outcome 19 Intervention failure.

19.1 First‐generation SU

1

409

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.44, 1.19]

19.2 Second‐generation SU

3

385

Risk Ratio (M‐H, Random, 95% CI)

0.13 [0.04, 0.44]

19.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Open in table viewer
Comparison 2. Sulphonylureas versus metformin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

8

3768

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.61, 1.58]
Analysis 2.1
Comparison 2 Sulphonylureas versus metformin, Outcome 1 All‐cause mortality.

Comparison 2 Sulphonylureas versus metformin, Outcome 1 All‐cause mortality.

1.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.2 Second‐generation SU

6

3528

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.61, 1.58]

1.3 Third‐generation SU

2

240

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 All‐cause mortality; best‐worst case scenario Show forest plot

5

283

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.12, 4.45]
Analysis 2.2
Comparison 2 Sulphonylureas versus metformin, Outcome 2 All‐cause mortality; best‐worst case scenario.

Comparison 2 Sulphonylureas versus metformin, Outcome 2 All‐cause mortality; best‐worst case scenario.

2.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 Second‐generation SU

4

207

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.10, 10.25]

2.3 Third‐generation SU

1

76

Risk Ratio (M‐H, Random, 95% CI)

0.35 [0.01, 8.35]

3 All‐cause mortality; worst‐best case scenario Show forest plot

5

283

Risk Ratio (M‐H, Random, 95% CI)

1.81 [0.37, 8.71]
Analysis 2.3
Comparison 2 Sulphonylureas versus metformin, Outcome 3 All‐cause mortality; worst‐best case scenario.

Comparison 2 Sulphonylureas versus metformin, Outcome 3 All‐cause mortality; worst‐best case scenario.

3.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.2 Second‐generation SU

4

207

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.10, 10.25]

3.3 Third‐generation SU

1

76

Risk Ratio (M‐H, Random, 95% CI)

3.16 [0.34, 29.06]

4 Cardiovascular mortality Show forest plot

8

3768

Risk Ratio (M‐H, Random, 95% CI)

1.47 [0.54, 4.01]
Analysis 2.4
Comparison 2 Sulphonylureas versus metformin, Outcome 4 Cardiovascular mortality.

Comparison 2 Sulphonylureas versus metformin, Outcome 4 Cardiovascular mortality.

4.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4.2 Second‐generation SU

6

3528

Risk Ratio (M‐H, Random, 95% CI)

1.47 [0.54, 4.01]

4.3 Third‐generation SU

2

240

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Non‐fatal macrovascular outcomes Show forest plot

4

3094

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.48, 0.93]
Analysis 2.5
Comparison 2 Sulphonylureas versus metformin, Outcome 5 Non‐fatal macrovascular outcomes.

Comparison 2 Sulphonylureas versus metformin, Outcome 5 Non‐fatal macrovascular outcomes.

5.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5.2 Second‐generation SU

3

3018

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.48, 0.93]

5.3 Third‐generation SU

1

76

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Non‐fatal myocardial infarction Show forest plot

4

3061

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.37, 2.85]
Analysis 2.6
Comparison 2 Sulphonylureas versus metformin, Outcome 6 Non‐fatal myocardial infarction.

Comparison 2 Sulphonylureas versus metformin, Outcome 6 Non‐fatal myocardial infarction.

6.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6.2 Second‐generation SU

4

3061

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.37, 2.85]

6.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7 Non‐fatal stroke Show forest plot

1

44

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 2.7
Comparison 2 Sulphonylureas versus metformin, Outcome 7 Non‐fatal stroke.

Comparison 2 Sulphonylureas versus metformin, Outcome 7 Non‐fatal stroke.

7.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.2 Second‐generation SU

1

44

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 Amputation of lower extremity Show forest plot

1

44

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 2.8
Comparison 2 Sulphonylureas versus metformin, Outcome 8 Amputation of lower extremity.

Comparison 2 Sulphonylureas versus metformin, Outcome 8 Amputation of lower extremity.

8.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.2 Second‐generation SU

1

44

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9 Peripheral revascularisation Show forest plot

2

2946

Risk Ratio (M‐H, Random, 95% CI)

1.15 [0.69, 1.92]
Analysis 2.9
Comparison 2 Sulphonylureas versus metformin, Outcome 9 Peripheral revascularisation.

Comparison 2 Sulphonylureas versus metformin, Outcome 9 Peripheral revascularisation.

9.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.2 Second‐generation SU

2

2946

Risk Ratio (M‐H, Random, 95% CI)

1.15 [0.69, 1.92]

9.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10 Microvascular outcomes Show forest plot

1

44

Risk Ratio (M‐H, Random, 95% CI)

2.0 [0.20, 20.49]
Analysis 2.10
Comparison 2 Sulphonylureas versus metformin, Outcome 10 Microvascular outcomes.

Comparison 2 Sulphonylureas versus metformin, Outcome 10 Microvascular outcomes.

10.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.2 Second‐generation SU

1

44

Risk Ratio (M‐H, Random, 95% CI)

2.0 [0.20, 20.49]

10.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11 Nephropathy Show forest plot

1

44

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.07, 15.00]
Analysis 2.11
Comparison 2 Sulphonylureas versus metformin, Outcome 11 Nephropathy.

Comparison 2 Sulphonylureas versus metformin, Outcome 11 Nephropathy.

11.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.2 Second‐generation SU

1

44

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.07, 15.00]

11.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12 Retinal photocoagulation Show forest plot

1

44

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 2.12
Comparison 2 Sulphonylureas versus metformin, Outcome 12 Retinal photocoagulation.

Comparison 2 Sulphonylureas versus metformin, Outcome 12 Retinal photocoagulation.

12.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.2 Second‐generation SU

1

44

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13 Change in fasting blood glucose from baseline (mmol/L) Show forest plot

15

4654

Mean Difference (IV, Random, 95% CI)

0.20 [‐0.07, 0.48]
Analysis 2.13
Comparison 2 Sulphonylureas versus metformin, Outcome 13 Change in fasting blood glucose from baseline (mmol/L).

Comparison 2 Sulphonylureas versus metformin, Outcome 13 Change in fasting blood glucose from baseline (mmol/L).

13.1 First‐generation SU

2

482

Mean Difference (IV, Random, 95% CI)

0.13 [‐0.75, 1.01]

13.2 Second‐generation SU

11

3891

Mean Difference (IV, Random, 95% CI)

0.43 [0.10, 0.75]

13.3 Third‐generation SU

3

281

Mean Difference (IV, Random, 95% CI)

‐0.22 [‐0.52, 0.08]

14 Change in HbA1c from baseline (%) Show forest plot

13

3632

Mean Difference (IV, Random, 95% CI)

0.06 [‐0.16, 0.29]
Analysis 2.14
Comparison 2 Sulphonylureas versus metformin, Outcome 14 Change in HbA1c from baseline (%).

Comparison 2 Sulphonylureas versus metformin, Outcome 14 Change in HbA1c from baseline (%).

14.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

14.2 Second‐generation SU

10

3351

Mean Difference (IV, Random, 95% CI)

0.17 [‐0.09, 0.44]

14.3 Third‐generation SU

3

281

Mean Difference (IV, Random, 95% CI)

‐0.18 [‐0.43, 0.07]

15 Change in BMI from baseline (kg/m2) Show forest plot

5

322

Mean Difference (IV, Random, 95% CI)

0.13 [‐0.69, 0.94]
Analysis 2.15
Comparison 2 Sulphonylureas versus metformin, Outcome 15 Change in BMI from baseline (kg/m2).

Comparison 2 Sulphonylureas versus metformin, Outcome 15 Change in BMI from baseline (kg/m2).

15.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

15.2 Second‐generation SU

3

103

Mean Difference (IV, Random, 95% CI)

0.25 [‐1.21, 1.70]

15.3 Third‐generation SU

2

219

Mean Difference (IV, Random, 95% CI)

‐0.10 [‐1.06, 0.86]

16 Change in weight from baseline (kg) Show forest plot

7

3497

Mean Difference (IV, Random, 95% CI)

3.77 [3.06, 4.47]
Analysis 2.16
Comparison 2 Sulphonylureas versus metformin, Outcome 16 Change in weight from baseline (kg).

Comparison 2 Sulphonylureas versus metformin, Outcome 16 Change in weight from baseline (kg).

16.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

16.2 Second‐generation SU

7

3497

Mean Difference (IV, Random, 95% CI)

3.77 [3.06, 4.47]

16.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

17 Adverse events Show forest plot

5

3118

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.97, 1.01]
Analysis 2.17
Comparison 2 Sulphonylureas versus metformin, Outcome 17 Adverse events.

Comparison 2 Sulphonylureas versus metformin, Outcome 17 Adverse events.

17.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

17.2 Second‐generation SU

4

3042

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.97, 1.01]

17.3 Third‐generation SU

1

76

Risk Ratio (M‐H, Random, 95% CI)

3.16 [0.13, 75.16]

18 Serious adverse events Show forest plot

5

3175

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.82, 1.07]
Analysis 2.18
Comparison 2 Sulphonylureas versus metformin, Outcome 18 Serious adverse events.

Comparison 2 Sulphonylureas versus metformin, Outcome 18 Serious adverse events.

18.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

18.2 Second‐generation SU

4

3011

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.82, 1.07]

18.3 Third‐generation SU

1

164

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19 Drop‐outs due to adverse events Show forest plot

8

3731

Risk Ratio (M‐H, Random, 95% CI)

1.18 [0.98, 1.41]
Analysis 2.19
Comparison 2 Sulphonylureas versus metformin, Outcome 19 Drop‐outs due to adverse events.

Comparison 2 Sulphonylureas versus metformin, Outcome 19 Drop‐outs due to adverse events.

19.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19.2 Second‐generation SU

7

3567

Risk Ratio (M‐H, Random, 95% CI)

1.19 [0.99, 1.42]

19.3 Third‐generation SU

1

164

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.01, 4.20]

20 Mild hypoglycaemia Show forest plot

6

4827

Risk Ratio (M‐H, Fixed, 95% CI)

3.16 [2.74, 3.64]
Analysis 2.20
Comparison 2 Sulphonylureas versus metformin, Outcome 20 Mild hypoglycaemia.

Comparison 2 Sulphonylureas versus metformin, Outcome 20 Mild hypoglycaemia.

20.1 First‐generation SU

1

607

Risk Ratio (M‐H, Fixed, 95% CI)

1.89 [1.00, 3.58]

20.2 Second‐generation SU

5

4056

Risk Ratio (M‐H, Fixed, 95% CI)

3.24 [2.80, 3.76]

20.3 Third‐generation SU

1

164

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

21 Moderate hypoglycaemia Show forest plot

1

44

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.13, 69.87]
Analysis 2.21
Comparison 2 Sulphonylureas versus metformin, Outcome 21 Moderate hypoglycaemia.

Comparison 2 Sulphonylureas versus metformin, Outcome 21 Moderate hypoglycaemia.

21.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

21.2 Second‐generation SU

1

44

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.13, 69.87]

21.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

22 Severe hypoglycaemia Show forest plot

5

4408

Risk Ratio (M‐H, Random, 95% CI)

4.50 [1.24, 16.31]
Analysis 2.22
Comparison 2 Sulphonylureas versus metformin, Outcome 22 Severe hypoglycaemia.

Comparison 2 Sulphonylureas versus metformin, Outcome 22 Severe hypoglycaemia.

22.1 First‐generation SU

1

607

Risk Ratio (M‐H, Random, 95% CI)

2.58 [0.24, 28.31]

22.2 Second‐generation SU

4

3637

Risk Ratio (M‐H, Random, 95% CI)

5.64 [1.22, 26.00]

22.3 Third‐generation SU

1

164

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23 Cancer Show forest plot

1

2902

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.76, 1.61]
Analysis 2.23
Comparison 2 Sulphonylureas versus metformin, Outcome 23 Cancer.

Comparison 2 Sulphonylureas versus metformin, Outcome 23 Cancer.

23.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.2 Second‐generation SU

1

2902

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.76, 1.61]

23.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24 Intervention failure Show forest plot

9

4990

Risk Ratio (M‐H, Random, 95% CI)

0.92 [0.60, 1.39]
Analysis 2.24
Comparison 2 Sulphonylureas versus metformin, Outcome 24 Intervention failure.

Comparison 2 Sulphonylureas versus metformin, Outcome 24 Intervention failure.

24.1 First‐generation SU

1

607

Risk Ratio (M‐H, Random, 95% CI)

0.63 [0.36, 1.09]

24.2 Second‐generation SU

7

4143

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.60, 1.57]

24.3 Third‐generation SU

2

240

Risk Ratio (M‐H, Random, 95% CI)

1.23 [0.43, 3.50]
Open in table viewer
Comparison 3. Sulphonylureas versus thiazolidinediones

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

8

5030

Risk Ratio (M‐H, Random, 95% CI)

0.92 [0.60, 1.41]
Analysis 3.1
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 1 All‐cause mortality.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 1 All‐cause mortality.

1.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.2 Second‐generation SU

7

4955

Risk Ratio (M‐H, Random, 95% CI)

0.92 [0.60, 1.41]

1.3 Third‐generation SU

1

75

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 All‐cause mortality; best‐worst case scenario Show forest plot

5

1327

Risk Ratio (M‐H, Random, 95% CI)

0.18 [0.06, 0.54]
Analysis 3.2
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 2 All‐cause mortality; best‐worst case scenario.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 2 All‐cause mortality; best‐worst case scenario.

2.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 Second‐generation SU

4

1252

Risk Ratio (M‐H, Random, 95% CI)

0.18 [0.06, 0.54]

2.3 Third‐generation SU

1

75

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 All‐cause mortality; worst‐best case scenario Show forest plot

5

1327

Risk Ratio (M‐H, Random, 95% CI)

7.49 [1.39, 40.18]
Analysis 3.3
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 3 All‐cause mortality; worst‐best case scenario.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 3 All‐cause mortality; worst‐best case scenario.

3.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.2 Second‐generation SU

4

1252

Risk Ratio (M‐H, Random, 95% CI)

9.76 [0.59, 161.27]

3.3 Third‐generation SU

1

75

Risk Ratio (M‐H, Random, 95% CI)

7.18 [0.38, 134.45]

4 Cardiovascular mortality Show forest plot

8

5030

Risk Ratio (M‐H, Random, 95% CI)

1.30 [0.55, 3.07]
Analysis 3.4
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 4 Cardiovascular mortality.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 4 Cardiovascular mortality.

4.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4.2 Second‐generation SU

7

4955

Risk Ratio (M‐H, Random, 95% CI)

1.30 [0.55, 3.07]

4.3 Third‐generation SU

1

75

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Non‐fatal macrovascular outcomes Show forest plot

7

4675

Risk Ratio (M‐H, Random, 95% CI)

0.91 [0.62, 1.33]
Analysis 3.5
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 5 Non‐fatal macrovascular outcomes.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 5 Non‐fatal macrovascular outcomes.

5.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5.2 Second‐generation SU

6

4600

Risk Ratio (M‐H, Random, 95% CI)

0.91 [0.62, 1.33]

5.3 Third‐generation SU

1

75

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Non‐fatal myocardial infarction Show forest plot

7

4956

Risk Ratio (M‐H, Random, 95% CI)

0.68 [0.41, 1.14]
Analysis 3.6
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 6 Non‐fatal myocardial infarction.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 6 Non‐fatal myocardial infarction.

6.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6.2 Second‐generation SU

7

4956

Risk Ratio (M‐H, Random, 95% CI)

0.68 [0.41, 1.14]

6.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7 Non‐fatal stroke Show forest plot

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.02, 1.67]
Analysis 3.7
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 7 Non‐fatal stroke.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 7 Non‐fatal stroke.

7.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.2 Second‐generation SU

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.02, 1.67]

7.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 Amputation of lower extremity Show forest plot

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 3.8
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 8 Amputation of lower extremity.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 8 Amputation of lower extremity.

8.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.2 Second‐generation SU

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9 Cardial revascularisation Show forest plot

2

707

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.61, 1.71]
Analysis 3.9
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 9 Cardial revascularisation.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 9 Cardial revascularisation.

9.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.2 Second‐generation SU

2

707

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.61, 1.71]

9.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10 Peripheral revascularisation Show forest plot

3

3612

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.54, 1.39]
Analysis 3.10
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 10 Peripheral revascularisation.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 10 Peripheral revascularisation.

10.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.2 Second‐generation SU

3

3612

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.54, 1.39]

10.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11 Microvascular outcomes Show forest plot

2

235

Risk Ratio (M‐H, Random, 95% CI)

0.83 [0.05, 13.16]
Analysis 3.11
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 11 Microvascular outcomes.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 11 Microvascular outcomes.

11.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.2 Second‐generation SU

2

235

Risk Ratio (M‐H, Random, 95% CI)

0.83 [0.05, 13.16]

11.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12 Nephropathy Show forest plot

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.11 [0.01, 2.02]
Analysis 3.12
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 12 Nephropathy.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 12 Nephropathy.

12.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.2 Second‐generation SU

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.11 [0.01, 2.02]

12.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13 Retinopathy Show forest plot

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.06, 15.64]
Analysis 3.13
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 13 Retinopathy.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 13 Retinopathy.

13.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13.2 Second‐generation SU

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.06, 15.64]

13.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14 Retinal photocoagulation Show forest plot

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 3.14
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 14 Retinal photocoagulation.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 14 Retinal photocoagulation.

14.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.2 Second‐generation SU

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

15 Change in fasting blood glucose from baseline (mmol/L) Show forest plot

18

6731

Mean Difference (IV, Random, 95% CI)

0.53 [0.31, 0.75]
Analysis 3.15
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 15 Change in fasting blood glucose from baseline (mmol/L).

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 15 Change in fasting blood glucose from baseline (mmol/L).

15.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

15.2 Second‐generation SU

14

6076

Mean Difference (IV, Random, 95% CI)

0.56 [0.33, 0.79]

15.3 Third‐generation SU

4

655

Mean Difference (IV, Random, 95% CI)

0.46 [‐0.22, 1.13]

16 Change in HbA1c from baseline (%) Show forest plot

21

7435

Mean Difference (IV, Random, 95% CI)

0.03 [‐0.10, 0.16]
Analysis 3.16
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 16 Change in HbA1c from baseline (%).

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 16 Change in HbA1c from baseline (%).

16.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

16.2 Second‐generation SU

17

6776

Mean Difference (IV, Random, 95% CI)

0.06 [‐0.09, 0.20]

16.3 Third‐generation SU

4

659

Mean Difference (IV, Random, 95% CI)

‐0.09 [‐0.31, 0.14]

17 Change in BMI from baseline (kg/m2) Show forest plot

7

532

Mean Difference (IV, Random, 95% CI)

‐0.98 [‐1.18, ‐0.79]
Analysis 3.17
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 17 Change in BMI from baseline (kg/m2).

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 17 Change in BMI from baseline (kg/m2).

17.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

17.2 Second‐generation SU

4

121

Mean Difference (IV, Random, 95% CI)

1.00 [‐1.20, ‐0.80]

17.3 Third‐generation SU

3

411

Mean Difference (IV, Random, 95% CI)

‐0.75 [‐1.58, 0.08]

18 Change in weight from baseline (kg) Show forest plot

11

5948

Mean Difference (IV, Random, 95% CI)

‐1.86 [‐2.50, ‐1.21]
Analysis 3.18
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 18 Change in weight from baseline (kg).

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 18 Change in weight from baseline (kg).

18.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

18.2 Second‐generation SU

10

5779

Mean Difference (IV, Random, 95% CI)

‐1.90 [‐2.56, ‐1.25]

18.3 Third‐generation SU

1

169

Mean Difference (IV, Random, 95% CI)

0.20 [‐3.75, 4.15]

19 Adverse events Show forest plot

13

7001

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.94, 1.01]
Analysis 3.19
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 19 Adverse events.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 19 Adverse events.

19.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19.2 Second‐generation SU

10

6491

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.97, 1.01]

19.3 Third‐generation SU

3

510

Risk Ratio (M‐H, Random, 95% CI)

0.88 [0.78, 0.99]

20 Serious adverse events Show forest plot

11

5605

Risk Ratio (M‐H, Random, 95% CI)

0.90 [0.80, 1.01]
Analysis 3.20
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 20 Serious adverse events.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 20 Serious adverse events.

20.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

20.2 Second‐generation SU

8

4979

Risk Ratio (M‐H, Random, 95% CI)

0.90 [0.80, 1.01]

20.3 Third‐generation SU

3

626

Risk Ratio (M‐H, Random, 95% CI)

0.61 [0.21, 1.83]

21 Drop‐outs due to adverse events Show forest plot

17

7856

Risk Ratio (M‐H, Random, 95% CI)

1.16 [1.00, 1.34]
Analysis 3.21
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 21 Drop‐outs due to adverse events.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 21 Drop‐outs due to adverse events.

21.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

21.2 Second‐generation SU

15

7433

Risk Ratio (M‐H, Random, 95% CI)

1.15 [0.98, 1.36]

21.3 Third‐generation SU

2

423

Risk Ratio (M‐H, Random, 95% CI)

0.54 [0.15, 1.97]

22 Mild hypoglycaemia Show forest plot

9

6556

Risk Ratio (M‐H, Random, 95% CI)

3.95 [3.08, 5.06]
Analysis 3.22
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 22 Mild hypoglycaemia.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 22 Mild hypoglycaemia.

22.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

22.2 Second‐generation SU

8

6365

Risk Ratio (M‐H, Random, 95% CI)

4.05 [3.28, 5.00]

22.3 Third‐generation SU

1

191

Risk Ratio (M‐H, Random, 95% CI)

1.41 [0.47, 4.30]

23 Moderate hypoglycaemia Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 3.23
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 23 Moderate hypoglycaemia.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 23 Moderate hypoglycaemia.

23.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24 Severe hypoglycaemia Show forest plot

8

6030

Risk Ratio (M‐H, Random, 95% CI)

6.11 [1.57, 23.79]
Analysis 3.24
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 24 Severe hypoglycaemia.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 24 Severe hypoglycaemia.

24.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24.2 Second‐generation SU

6

5660

Risk Ratio (M‐H, Random, 95% CI)

6.11 [1.57, 23.79]

24.3 Third‐generation SU

2

370

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

25 Cancer Show forest plot

6

4912

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.72, 1.45]
Analysis 3.25
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 25 Cancer.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 25 Cancer.

25.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

25.2 Second‐generation SU

6

4912

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.72, 1.45]

25.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

26 Intervention failure Show forest plot

10

6757

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.65, 1.45]
Analysis 3.26
Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 26 Intervention failure.

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 26 Intervention failure.

26.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

26.2 Second‐generation SU

8

6438

Risk Ratio (M‐H, Random, 95% CI)

1.10 [0.73, 1.65]

26.3 Third‐generation SU

2

319

Risk Ratio (M‐H, Random, 95% CI)

0.24 [0.08, 0.75]
Open in table viewer
Comparison 4. Sulphonylureas versus insulin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

5

3586

Risk Ratio (M‐H, Random, 95% CI)

1.05 [0.92, 1.21]
Analysis 4.1
Comparison 4 Sulphonylureas versus insulin, Outcome 1 All‐cause mortality.

Comparison 4 Sulphonylureas versus insulin, Outcome 1 All‐cause mortality.

1.1 First‐generation SU

2

1944

Risk Ratio (M‐H, Random, 95% CI)

1.18 [0.88, 1.59]

1.2 Second‐generation SU

4

1642

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.79, 1.18]

1.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 All‐cause mortality; best‐worst case scenario Show forest plot

2

80

Risk Ratio (M‐H, Random, 95% CI)

0.13 [0.02, 0.95]
Analysis 4.2
Comparison 4 Sulphonylureas versus insulin, Outcome 2 All‐cause mortality; best‐worst case scenario.

Comparison 4 Sulphonylureas versus insulin, Outcome 2 All‐cause mortality; best‐worst case scenario.

2.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 Second‐generation SU

2

80

Risk Ratio (M‐H, Random, 95% CI)

0.13 [0.02, 0.95]

2.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 All‐cause mortality; worst‐best case scenario Show forest plot

2

80

Risk Ratio (M‐H, Random, 95% CI)

3.54 [0.83, 15.00]
Analysis 4.3
Comparison 4 Sulphonylureas versus insulin, Outcome 3 All‐cause mortality; worst‐best case scenario.

Comparison 4 Sulphonylureas versus insulin, Outcome 3 All‐cause mortality; worst‐best case scenario.

3.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.2 Second‐generation SU

2

80

Risk Ratio (M‐H, Random, 95% CI)

3.54 [0.83, 15.00]

3.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4 Cardiovascular mortality Show forest plot

5

3586

Risk Ratio (M‐H, Random, 95% CI)

1.09 [0.82, 1.44]
Analysis 4.4
Comparison 4 Sulphonylureas versus insulin, Outcome 4 Cardiovascular mortality.

Comparison 4 Sulphonylureas versus insulin, Outcome 4 Cardiovascular mortality.

4.1 First‐generation SU

2

1944

Risk Ratio (M‐H, Random, 95% CI)

1.36 [0.68, 2.71]

4.2 Second‐generation SU

4

1642

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.73, 1.28]

4.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Non‐fatal myocardial infarction Show forest plot

2

3470

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.79, 1.23]
Analysis 4.5
Comparison 4 Sulphonylureas versus insulin, Outcome 5 Non‐fatal myocardial infarction.

Comparison 4 Sulphonylureas versus insulin, Outcome 5 Non‐fatal myocardial infarction.

5.1 First‐generation SU

2

1944

Risk Ratio (M‐H, Random, 95% CI)

1.08 [0.81, 1.45]

5.2 Second‐generation SU

1

1526

Risk Ratio (M‐H, Random, 95% CI)

0.86 [0.61, 1.22]

5.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Non‐fatal stroke Show forest plot

2

3470

Risk Ratio (M‐H, Random, 95% CI)

1.45 [1.02, 2.06]
Analysis 4.6
Comparison 4 Sulphonylureas versus insulin, Outcome 6 Non‐fatal stroke.

Comparison 4 Sulphonylureas versus insulin, Outcome 6 Non‐fatal stroke.

6.1 First‐generation SU

2

1944

Risk Ratio (M‐H, Random, 95% CI)

1.23 [0.74, 2.05]

6.2 Second‐generation SU

1

1526

Risk Ratio (M‐H, Random, 95% CI)

1.68 [1.04, 2.71]

6.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7 Amputation of lower extremity Show forest plot

2

3470

Risk Ratio (M‐H, Random, 95% CI)

0.49 [0.24, 1.00]
Analysis 4.7
Comparison 4 Sulphonylureas versus insulin, Outcome 7 Amputation of lower extremity.

Comparison 4 Sulphonylureas versus insulin, Outcome 7 Amputation of lower extremity.

7.1 First‐generation SU

2

1944

Risk Ratio (M‐H, Random, 95% CI)

0.49 [0.18, 1.34]

7.2 Second‐generation SU

1

1526

Risk Ratio (M‐H, Random, 95% CI)

0.49 [0.18, 1.35]

7.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 Microvascular outcomes Show forest plot

1

3056

Risk Ratio (M‐H, Random, 95% CI)

1.12 [0.82, 1.53]
Analysis 4.8
Comparison 4 Sulphonylureas versus insulin, Outcome 8 Microvascular outcomes.

Comparison 4 Sulphonylureas versus insulin, Outcome 8 Microvascular outcomes.

8.1 First‐generation SU

1

1530

Risk Ratio (M‐H, Random, 95% CI)

1.30 [0.95, 1.77]

8.2 Second‐generation SU

1

1526

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.67, 1.33]

8.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9 Nephropathy Show forest plot

1

414

Risk Ratio (M‐H, Random, 95% CI)

11.32 [0.63, 203.45]
Analysis 4.9
Comparison 4 Sulphonylureas versus insulin, Outcome 9 Nephropathy.

Comparison 4 Sulphonylureas versus insulin, Outcome 9 Nephropathy.

9.1 First‐generation SU

1

414

Risk Ratio (M‐H, Random, 95% CI)

11.32 [0.63, 203.45]

9.2 Second‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10 Retinopathy Show forest plot

1

414

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.71, 1.39]
Analysis 4.10
Comparison 4 Sulphonylureas versus insulin, Outcome 10 Retinopathy.

Comparison 4 Sulphonylureas versus insulin, Outcome 10 Retinopathy.

10.1 First‐generation SU

1

414

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.71, 1.39]

10.2 Second‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11 Retinal photocoagulation Show forest plot

1

3056

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.80, 1.31]
Analysis 4.11
Comparison 4 Sulphonylureas versus insulin, Outcome 11 Retinal photocoagulation.

Comparison 4 Sulphonylureas versus insulin, Outcome 11 Retinal photocoagulation.

11.1 First‐generation SU

1

1530

Risk Ratio (M‐H, Random, 95% CI)

1.12 [0.80, 1.57]

11.2 Second‐generation SU

1

1526

Risk Ratio (M‐H, Random, 95% CI)

0.93 [0.65, 1.32]

11.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12 Change in fasting blood glucose from baseline (mmol/L) Show forest plot

5

2423

Mean Difference (IV, Random, 95% CI)

0.12 [‐0.37, 0.61]
Analysis 4.12
Comparison 4 Sulphonylureas versus insulin, Outcome 12 Change in fasting blood glucose from baseline (mmol/L).

Comparison 4 Sulphonylureas versus insulin, Outcome 12 Change in fasting blood glucose from baseline (mmol/L).

12.1 First‐generation SU

1

1122

Mean Difference (IV, Random, 95% CI)

‐0.40 [‐0.69, ‐0.11]

12.2 Second‐generation SU

5

1301

Mean Difference (IV, Random, 95% CI)

0.29 [‐0.02, 0.61]

12.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

13 Change in HbA1c from baseline (%) Show forest plot

6

2566

Mean Difference (IV, Random, 95% CI)

‐0.09 [‐0.20, 0.03]
Analysis 4.13
Comparison 4 Sulphonylureas versus insulin, Outcome 13 Change in HbA1c from baseline (%).

Comparison 4 Sulphonylureas versus insulin, Outcome 13 Change in HbA1c from baseline (%).

13.1 First‐generation SU

1

1122

Mean Difference (IV, Random, 95% CI)

‐0.20 [‐0.38, ‐0.02]

13.2 Second‐generation SU

6

1444

Mean Difference (IV, Random, 95% CI)

‐0.03 [‐0.17, 0.10]

13.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

14 Change in BMI from baseline (kg/m2) Show forest plot

1

34

Mean Difference (IV, Random, 95% CI)

‐1.70 [‐4.10, 0.70]
Analysis 4.14
Comparison 4 Sulphonylureas versus insulin, Outcome 14 Change in BMI from baseline (kg/m2).

Comparison 4 Sulphonylureas versus insulin, Outcome 14 Change in BMI from baseline (kg/m2).

14.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

14.2 Second‐generation SU

1

34

Mean Difference (IV, Random, 95% CI)

‐1.70 [‐4.10, 0.70]

14.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

15 Change in weight from baseline (kg) Show forest plot

5

2514

Mean Difference (IV, Random, 95% CI)

1.00 [‐2.82, 0.83]
Analysis 4.15
Comparison 4 Sulphonylureas versus insulin, Outcome 15 Change in weight from baseline (kg).

Comparison 4 Sulphonylureas versus insulin, Outcome 15 Change in weight from baseline (kg).

15.1 First‐generation SU

1

1122

Mean Difference (IV, Random, 95% CI)

‐2.30 [‐4.11, ‐0.49]

15.2 Second‐generation SU

5

1392

Mean Difference (IV, Random, 95% CI)

‐0.37 [‐2.39, 1.65]

15.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

16 Adverse events Show forest plot

1

143

Risk Ratio (M‐H, Random, 95% CI)

1.06 [0.68, 1.65]
Analysis 4.16
Comparison 4 Sulphonylureas versus insulin, Outcome 16 Adverse events.

Comparison 4 Sulphonylureas versus insulin, Outcome 16 Adverse events.

16.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

16.2 Second‐generation SU

1

143

Risk Ratio (M‐H, Random, 95% CI)

1.06 [0.68, 1.65]

16.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

17 Drop‐outs due to adverse events Show forest plot

2

192

Risk Ratio (M‐H, Random, 95% CI)

3.54 [0.43, 29.43]
Analysis 4.17
Comparison 4 Sulphonylureas versus insulin, Outcome 17 Drop‐outs due to adverse events.

Comparison 4 Sulphonylureas versus insulin, Outcome 17 Drop‐outs due to adverse events.

17.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

17.2 Second‐generation SU

2

192

Risk Ratio (M‐H, Random, 95% CI)

3.54 [0.43, 29.43]

17.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

18 Mild hypoglycaemia Show forest plot

2

3105

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.45, 1.95]
Analysis 4.18
Comparison 4 Sulphonylureas versus insulin, Outcome 18 Mild hypoglycaemia.

Comparison 4 Sulphonylureas versus insulin, Outcome 18 Mild hypoglycaemia.

18.1 First‐generation SU

1

1530

Risk Ratio (M‐H, Random, 95% CI)

0.57 [0.42, 0.78]

18.2 Second‐generation SU

2

1575

Risk Ratio (M‐H, Random, 95% CI)

1.41 [1.13, 1.76]

18.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19 Severe hypoglycaemia Show forest plot

4

3172

Risk Ratio (M‐H, Random, 95% CI)

1.27 [0.38, 4.24]
Analysis 4.19
Comparison 4 Sulphonylureas versus insulin, Outcome 19 Severe hypoglycaemia.

Comparison 4 Sulphonylureas versus insulin, Outcome 19 Severe hypoglycaemia.

19.1 First‐generation SU

1

1530

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.11, 3.02]

19.2 Second‐generation SU

4

1642

Risk Ratio (M‐H, Random, 95% CI)

2.07 [0.66, 6.50]

19.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

20 Cancer Show forest plot

3

3519

Risk Ratio (M‐H, Random, 95% CI)

1.01 [0.75, 1.36]
Analysis 4.20
Comparison 4 Sulphonylureas versus insulin, Outcome 20 Cancer.

Comparison 4 Sulphonylureas versus insulin, Outcome 20 Cancer.

20.1 First‐generation SU

2

1944

Risk Ratio (M‐H, Random, 95% CI)

0.81 [0.29, 2.27]

20.2 Second‐generation SU

2

1575

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.61, 1.49]

20.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

21 Intervention failure Show forest plot

4

3200

Risk Ratio (M‐H, Random, 95% CI)

1.24 [0.67, 2.27]
Analysis 4.21
Comparison 4 Sulphonylureas versus insulin, Outcome 21 Intervention failure.

Comparison 4 Sulphonylureas versus insulin, Outcome 21 Intervention failure.

21.1 First‐generation SU

1

1530

Risk Ratio (M‐H, Random, 95% CI)

0.62 [0.44, 0.89]

21.2 Second‐generation SU

4

1670

Risk Ratio (M‐H, Random, 95% CI)

1.96 [0.80, 4.76]

21.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Open in table viewer
Comparison 5. Sulphonylureas versus alpha‐glucosidase inhibitors

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

6

714

Risk Ratio (M‐H, Random, 95% CI)

2.25 [0.43, 11.84]
Analysis 5.1
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 1 All‐cause mortality.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 1 All‐cause mortality.

1.1 First‐generation SU

2

246

Risk Ratio (M‐H, Random, 95% CI)

3.16 [0.13, 76.44]

1.2 Second‐generation SU

4

468

Risk Ratio (M‐H, Random, 95% CI)

1.98 [0.28, 13.86]

1.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 All‐cause mortality; best‐worst case scenario Show forest plot

2

90

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 5.2
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 2 All‐cause mortality; best‐worst case scenario.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 2 All‐cause mortality; best‐worst case scenario.

2.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 Second‐generation SU

2

90

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 All‐cause mortality; worst‐best case scenario Show forest plot

2

90

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 5.3
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 3 All‐cause mortality; worst‐best case scenario.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 3 All‐cause mortality; worst‐best case scenario.

3.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.2 Second‐generation SU

2

90

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4 Cardiovascular mortality Show forest plot

6

708

Risk Ratio (M‐H, Random, 95% CI)

2.39 [0.30, 19.28]
Analysis 5.4
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 4 Cardiovascular mortality.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 4 Cardiovascular mortality.

4.1 First‐generation SU

2

242

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.12, 72.44]

4.2 Second‐generation SU

4

466

Risk Ratio (M‐H, Random, 95% CI)

2.02 [0.13, 31.96]

4.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Non‐fatal macrovascular outcomes Show forest plot

2

345

Risk Ratio (M‐H, Random, 95% CI)

1.61 [1.06, 2.44]
Analysis 5.5
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 5 Non‐fatal macrovascular outcomes.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 5 Non‐fatal macrovascular outcomes.

5.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5.2 Second‐generation SU

2

345

Risk Ratio (M‐H, Random, 95% CI)

1.61 [1.06, 2.44]

5.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Non‐fatal myocardial infarction Show forest plot

2

133

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.06, 14.92]
Analysis 5.6
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 6 Non‐fatal myocardial infarction.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 6 Non‐fatal myocardial infarction.

6.1 First‐generation SU

1

98

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.06, 14.92]

6.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7 Non‐fatal stroke Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 5.7
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 7 Non‐fatal stroke.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 7 Non‐fatal stroke.

7.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 Amputation of lower extremity Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 5.8
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 8 Amputation of lower extremity.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 8 Amputation of lower extremity.

8.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9 Cardial revascularisation Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 5.9
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 9 Cardial revascularisation.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 9 Cardial revascularisation.

9.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10 Peripheral revascularisation Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 5.10
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 10 Peripheral revascularisation.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 10 Peripheral revascularisation.

10.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11 Microvascular outcomes Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 5.11
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 11 Microvascular outcomes.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 11 Microvascular outcomes.

11.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12 Nephropathy Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 5.12
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 12 Nephropathy.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 12 Nephropathy.

12.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13 Retinopathy Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 5.13
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 13 Retinopathy.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 13 Retinopathy.

13.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14 Retinal photocoagulation Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 5.14
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 14 Retinal photocoagulation.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 14 Retinal photocoagulation.

14.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

15 Change in fasting blood glucose from baseline (mmol/L) Show forest plot

11

915

Mean Difference (IV, Random, 95% CI)

‐0.46 [‐0.80, ‐0.11]
Analysis 5.15
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 15 Change in fasting blood glucose from baseline (mmol/L).

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 15 Change in fasting blood glucose from baseline (mmol/L).

15.1 First‐generation SU

2

208

Mean Difference (IV, Random, 95% CI)

‐1.16 [‐1.92, ‐0.41]

15.2 Second‐generation SU

8

488

Mean Difference (IV, Random, 95% CI)

‐0.16 [‐0.42, 0.11]

15.3 Third‐generation SU

1

219

Mean Difference (IV, Random, 95% CI)

‐1.20 [‐1.92, ‐0.48]

16 Change in HbA1c from baseline (%) Show forest plot

13

968

Mean Difference (IV, Random, 95% CI)

‐0.20 [‐0.46, 0.06]
Analysis 5.16
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 16 Change in HbA1c from baseline (%).

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 16 Change in HbA1c from baseline (%).

16.1 First‐generation SU

2

208

Mean Difference (IV, Random, 95% CI)

‐0.50 [‐0.79, ‐0.20]

16.2 Second‐generation SU

10

541

Mean Difference (IV, Random, 95% CI)

‐0.06 [‐0.36, 0.24]

16.3 Third‐generation SU

1

219

Mean Difference (IV, Random, 95% CI)

‐0.7 [‐1.28, ‐0.12]

17 Change in BMI from baseline (kg/m2) Show forest plot

5

232

Mean Difference (IV, Random, 95% CI)

‐0.02 [‐0.20, 0.16]
Analysis 5.17
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 17 Change in BMI from baseline (kg/m2).

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 17 Change in BMI from baseline (kg/m2).

17.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

17.2 Second‐generation SU

5

232

Mean Difference (IV, Random, 95% CI)

‐0.02 [‐0.20, 0.16]

17.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

18 Change in weight from baseline (kg) Show forest plot

7

689

Mean Difference (IV, Random, 95% CI)

0.81 [‐0.61, 2.23]
Analysis 5.18
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 18 Change in weight from baseline (kg).

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 18 Change in weight from baseline (kg).

18.1 First‐generation SU

1

132

Mean Difference (IV, Random, 95% CI)

3.2 [2.29, 4.11]

18.2 Second‐generation SU

5

338

Mean Difference (IV, Random, 95% CI)

‐0.22 [‐0.47, 0.03]

18.3 Third‐generation SU

1

219

Mean Difference (IV, Random, 95% CI)

1.5 [0.28, 2.72]

19 Adverse events Show forest plot

11

1111

Risk Ratio (M‐H, Random, 95% CI)

0.65 [0.51, 0.82]
Analysis 5.19
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 19 Adverse events.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 19 Adverse events.

19.1 First‐generation SU

2

246

Risk Ratio (M‐H, Random, 95% CI)

0.63 [0.52, 0.76]

19.2 Second‐generation SU

8

646

Risk Ratio (M‐H, Random, 95% CI)

0.64 [0.39, 1.03]

19.3 Third‐generation SU

1

219

Risk Ratio (M‐H, Random, 95% CI)

0.64 [0.53, 0.78]

20 Serious adverse events Show forest plot

3

229

Risk Ratio (M‐H, Random, 95% CI)

0.52 [0.09, 3.03]
Analysis 5.20
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 20 Serious adverse events.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 20 Serious adverse events.

20.1 First‐generation SU

1

98

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.14, 6.55]

20.2 Second‐generation SU

2

131

Risk Ratio (M‐H, Random, 95% CI)

0.15 [0.01, 2.81]

20.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

21 Drop‐outs due to adverse events Show forest plot

12

1335

Risk Ratio (M‐H, Random, 95% CI)

0.37 [0.22, 0.63]
Analysis 5.21
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 21 Drop‐outs due to adverse events.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 21 Drop‐outs due to adverse events.

21.1 First‐generation SU

2

246

Risk Ratio (M‐H, Random, 95% CI)

0.28 [0.12, 0.67]

21.2 Second‐generation SU

9

870

Risk Ratio (M‐H, Random, 95% CI)

0.48 [0.24, 0.96]

21.3 Third‐generation SU

1

219

Risk Ratio (M‐H, Random, 95% CI)

0.19 [0.02, 1.64]

22 Mild hypoglycaemia Show forest plot

6

636

Risk Ratio (M‐H, Random, 95% CI)

8.59 [2.62, 28.12]
Analysis 5.22
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 22 Mild hypoglycaemia.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 22 Mild hypoglycaemia.

22.1 First‐generation SU

1

98

Risk Ratio (M‐H, Random, 95% CI)

2.88 [0.12, 69.07]

22.2 Second‐generation SU

4

319

Risk Ratio (M‐H, Random, 95% CI)

12.63 [0.73, 219.86]

22.3 Third‐generation SU

1

219

Risk Ratio (M‐H, Random, 95% CI)

9.73 [2.33, 40.63]

23 Moderate hypoglycaemia Show forest plot

3

183

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 5.23
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 23 Moderate hypoglycaemia.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 23 Moderate hypoglycaemia.

23.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.2 Second‐generation SU

3

183

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24 Severe hypoglycaemia Show forest plot

5

500

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 5.24
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 24 Severe hypoglycaemia.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 24 Severe hypoglycaemia.

24.1 First‐generation SU

1

98

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24.2 Second‐generation SU

3

183

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24.3 Third‐generation SU

1

219

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

25 Cancer Show forest plot

3

443

Risk Ratio (M‐H, Random, 95% CI)

0.90 [0.11, 7.27]
Analysis 5.25
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 25 Cancer.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 25 Cancer.

25.1 First‐generation SU

1

98

Risk Ratio (M‐H, Random, 95% CI)

0.32 [0.01, 7.67]

25.2 Second‐generation SU

2

345

Risk Ratio (M‐H, Random, 95% CI)

1.98 [0.13, 31.35]

25.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

26 Intervention failure Show forest plot

5

831

Risk Ratio (M‐H, Random, 95% CI)

0.32 [0.18, 0.57]
Analysis 5.26
Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 26 Intervention failure.

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 26 Intervention failure.

26.1 First‐generation SU

1

98

Risk Ratio (M‐H, Random, 95% CI)

0.32 [0.01, 7.67]

26.2 Second‐generation SU

3

514

Risk Ratio (M‐H, Random, 95% CI)

0.25 [0.07, 0.92]

26.3 Third‐generation SU

1

219

Risk Ratio (M‐H, Random, 95% CI)

0.34 [0.17, 0.65]
Open in table viewer
Comparison 6. Sulphonylureas versus incretin‐based intervention

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

3

2249

Risk Ratio (M‐H, Random, 95% CI)

1.57 [0.62, 4.00]
Analysis 6.1
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 1 All‐cause mortality.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 1 All‐cause mortality.

1.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.2 Second‐generation SU

2

1503

Risk Ratio (M‐H, Random, 95% CI)

1.39 [0.52, 3.68]

1.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

6.01 [0.25, 147.05]

2 All‐cause mortality; best‐worst case scenario Show forest plot

1

1092

Risk Ratio (M‐H, Random, 95% CI)

0.39 [0.18, 0.84]
Analysis 6.2
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 2 All‐cause mortality; best‐worst case scenario.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 2 All‐cause mortality; best‐worst case scenario.

2.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 Second‐generation SU

1

1092

Risk Ratio (M‐H, Random, 95% CI)

0.39 [0.18, 0.84]

2.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 All‐cause mortality; worst‐best case scenario Show forest plot

1

1092

Risk Ratio (M‐H, Random, 95% CI)

3.67 [1.50, 8.97]
Analysis 6.3
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 3 All‐cause mortality; worst‐best case scenario.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 3 All‐cause mortality; worst‐best case scenario.

3.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.2 Second‐generation SU

1

1092

Risk Ratio (M‐H, Random, 95% CI)

3.67 [1.50, 8.97]

3.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4 Cardiovascular mortality Show forest plot

2

1157

Risk Ratio (M‐H, Random, 95% CI)

6.01 [0.25, 147.05]
Analysis 6.4
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 4 Cardiovascular mortality.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 4 Cardiovascular mortality.

4.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

6.01 [0.25, 147.05]

5 Non‐fatal macrovascular outcomes Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

1.61 [0.82, 3.17]
Analysis 6.5
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 5 Non‐fatal macrovascular outcomes.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 5 Non‐fatal macrovascular outcomes.

5.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

1.61 [0.82, 3.17]

5.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Non‐fatal myocardial infarction Show forest plot

2

1157

Risk Ratio (M‐H, Random, 95% CI)

0.66 [0.10, 4.19]
Analysis 6.6
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 6 Non‐fatal myocardial infarction.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 6 Non‐fatal myocardial infarction.

6.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.65 [0.03, 15.85]

6.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.07, 6.40]

7 Non‐fatal stroke Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

3.91 [0.36, 42.79]
Analysis 6.7
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 7 Non‐fatal stroke.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 7 Non‐fatal stroke.

7.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

3.91 [0.36, 42.79]

7.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 Amputation of lower extremity Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 6.8
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 8 Amputation of lower extremity.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 8 Amputation of lower extremity.

8.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9 Cardial revascularisation Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 6.9
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 9 Cardial revascularisation.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 9 Cardial revascularisation.

9.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10 Peripheral revascularisation Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 6.10
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 10 Peripheral revascularisation.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 10 Peripheral revascularisation.

10.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11 Microvascular outcomes Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

1.09 [0.52, 2.29]
Analysis 6.11
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 11 Microvascular outcomes.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 11 Microvascular outcomes.

11.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

1.09 [0.52, 2.29]

11.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12 Nephropathy Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.09, 10.70]
Analysis 6.12
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 12 Nephropathy.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 12 Nephropathy.

12.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.09, 10.70]

12.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13 Retinopathy Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

1.10 [0.50, 2.43]
Analysis 6.13
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 13 Retinopathy.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 13 Retinopathy.

13.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

1.10 [0.50, 2.43]

13.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14 Retinal photocoagulation Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 6.14
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 14 Retinal photocoagulation.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 14 Retinal photocoagulation.

14.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

15 Change in fasting blood glucose from baseline (mmol/L) Show forest plot

3

1948

Mean Difference (IV, Random, 95% CI)

0.34 [‐0.44, 1.13]
Analysis 6.15
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 15 Change in fasting blood glucose from baseline (mmol/L).

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 15 Change in fasting blood glucose from baseline (mmol/L).

15.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

15.2 Second‐generation SU

2

1202

Mean Difference (IV, Random, 95% CI)

0.11 [‐1.07, 1.28]

15.3 Third‐generation SU

1

746

Mean Difference (IV, Random, 95% CI)

0.8 [0.34, 1.26]

16 Change in HbA1c from baseline (%) Show forest plot

3

1950

Mean Difference (IV, Random, 95% CI)

0.35 [0.05, 0.64]
Analysis 6.16
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 16 Change in HbA1c from baseline (%).

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 16 Change in HbA1c from baseline (%).

16.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

16.2 Second‐generation SU

2

1204

Mean Difference (IV, Random, 95% CI)

0.26 [‐0.23, 0.75]

16.3 Third‐generation SU

1

746

Mean Difference (IV, Random, 95% CI)

0.5 [0.32, 0.68]

17 Change in BMI from baseline (kg/m2) Show forest plot

1

400

Mean Difference (IV, Random, 95% CI)

0.7 [0.52, 0.88]
Analysis 6.17
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 17 Change in BMI from baseline (kg/m2).

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 17 Change in BMI from baseline (kg/m2).

17.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

17.2 Second‐generation SU

1

400

Mean Difference (IV, Random, 95% CI)

0.7 [0.52, 0.88]

17.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

18 Change in weight from baseline (kg) Show forest plot

3

1952

Mean Difference (IV, Random, 95% CI)

1.96 [0.63, 3.28]
Analysis 6.18
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 18 Change in weight from baseline (kg).

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 18 Change in weight from baseline (kg).

18.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

18.2 Second‐generation SU

2

1206

Mean Difference (IV, Random, 95% CI)

1.31 [0.33, 2.29]

18.3 Third‐generation SU

1

746

Mean Difference (IV, Random, 95% CI)

3.30 [2.64, 3.96]

19 Adverse events Show forest plot

2

1157

Risk Ratio (M‐H, Random, 95% CI)

0.89 [0.74, 1.08]
Analysis 6.19
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 19 Adverse events.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 19 Adverse events.

19.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.90, 1.04]

19.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.73, 0.92]

20 Serious adverse events Show forest plot

2

1157

Risk Ratio (M‐H, Random, 95% CI)

1.22 [0.77, 1.94]
Analysis 6.20
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 20 Serious adverse events.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 20 Serious adverse events.

20.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

20.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

1.37 [0.71, 2.63]

20.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

1.09 [0.56, 2.10]

21 Drop‐outs due to adverse events Show forest plot

3

2249

Risk Ratio (M‐H, Random, 95% CI)

0.89 [0.64, 1.24]
Analysis 6.21
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 21 Drop‐outs due to adverse events.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 21 Drop‐outs due to adverse events.

21.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

21.2 Second‐generation SU

2

1503

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.67, 1.50]

21.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

0.70 [0.40, 1.24]

22 Mild hypoglycaemia Show forest plot

3

2249

Risk Ratio (M‐H, Random, 95% CI)

2.07 [1.44, 2.97]
Analysis 6.22
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 22 Mild hypoglycaemia.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 22 Mild hypoglycaemia.

22.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

22.2 Second‐generation SU

2

1503

Risk Ratio (M‐H, Random, 95% CI)

1.99 [1.02, 3.87]

22.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

2.41 [1.71, 3.40]

23 Severe hypoglycaemia Show forest plot

3

2249

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 6.23
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 23 Severe hypoglycaemia.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 23 Severe hypoglycaemia.

23.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.2 Second‐generation SU

2

1503

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24 Intervention failure Show forest plot

3

2249

Risk Ratio (M‐H, Random, 95% CI)

1.31 [0.56, 3.05]
Analysis 6.24
Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 24 Intervention failure.

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 24 Intervention failure.

24.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24.2 Second‐generation SU

2

1503

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.41, 2.43]

24.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

2.09 [1.22, 3.59]
Open in table viewer
Comparison 7. Sulphonylureas versus meglitinide

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

7

2038

Risk Ratio (M‐H, Random, 95% CI)

1.44 [0.47, 4.42]
Analysis 7.1
Comparison 7 Sulphonylureas versus meglitinide, Outcome 1 All‐cause mortality.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 1 All‐cause mortality.

1.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.2 Second‐generation SU

7

2038

Risk Ratio (M‐H, Random, 95% CI)

1.44 [0.47, 4.42]

1.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 All‐cause mortality; best‐worst case scenario Show forest plot

2

209

Risk Ratio (M‐H, Random, 95% CI)

0.07 [0.00, 1.16]
Analysis 7.2
Comparison 7 Sulphonylureas versus meglitinide, Outcome 2 All‐cause mortality; best‐worst case scenario.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 2 All‐cause mortality; best‐worst case scenario.

2.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 Second‐generation SU

2

209

Risk Ratio (M‐H, Random, 95% CI)

0.07 [0.00, 1.16]

2.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 All‐cause mortality; worst‐best case scenario Show forest plot

2

209

Risk Ratio (M‐H, Random, 95% CI)

15.17 [0.88, 261.61]
Analysis 7.3
Comparison 7 Sulphonylureas versus meglitinide, Outcome 3 All‐cause mortality; worst‐best case scenario.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 3 All‐cause mortality; worst‐best case scenario.

3.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.2 Second‐generation SU

2

209

Risk Ratio (M‐H, Random, 95% CI)

15.17 [0.88, 261.61]

3.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4 Cardiovascular mortality Show forest plot

7

2038

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.27, 3.53]
Analysis 7.4
Comparison 7 Sulphonylureas versus meglitinide, Outcome 4 Cardiovascular mortality.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 4 Cardiovascular mortality.

4.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4.2 Second‐generation SU

7

2038

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.27, 3.53]

4.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Non‐fatal macrovascular outcomes Show forest plot

3

866

Risk Ratio (M‐H, Random, 95% CI)

0.50 [0.20, 1.20]
Analysis 7.5
Comparison 7 Sulphonylureas versus meglitinide, Outcome 5 Non‐fatal macrovascular outcomes.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 5 Non‐fatal macrovascular outcomes.

5.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5.2 Second‐generation SU

3

866

Risk Ratio (M‐H, Random, 95% CI)

0.50 [0.20, 1.20]

5.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Non‐fatal myocardial infarction Show forest plot

3

726

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.26, 4.08]
Analysis 7.6
Comparison 7 Sulphonylureas versus meglitinide, Outcome 6 Non‐fatal myocardial infarction.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 6 Non‐fatal myocardial infarction.

6.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6.2 Second‐generation SU

3

726

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.26, 4.08]

6.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7 Non‐fatal stroke Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 7.7
Comparison 7 Sulphonylureas versus meglitinide, Outcome 7 Non‐fatal stroke.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 7 Non‐fatal stroke.

7.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 Amputation of lower extremity Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 7.8
Comparison 7 Sulphonylureas versus meglitinide, Outcome 8 Amputation of lower extremity.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 8 Amputation of lower extremity.

8.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9 Cardial revascularisation Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 7.9
Comparison 7 Sulphonylureas versus meglitinide, Outcome 9 Cardial revascularisation.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 9 Cardial revascularisation.

9.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10 Peripheral revascularisation Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 7.10
Comparison 7 Sulphonylureas versus meglitinide, Outcome 10 Peripheral revascularisation.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 10 Peripheral revascularisation.

10.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11 Microvascular outcomes Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 7.11
Comparison 7 Sulphonylureas versus meglitinide, Outcome 11 Microvascular outcomes.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 11 Microvascular outcomes.

11.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12 Nephropathy Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 7.12
Comparison 7 Sulphonylureas versus meglitinide, Outcome 12 Nephropathy.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 12 Nephropathy.

12.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13 Retinopathy Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 7.13
Comparison 7 Sulphonylureas versus meglitinide, Outcome 13 Retinopathy.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 13 Retinopathy.

13.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14 Retinal photocoagulation Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 7.14
Comparison 7 Sulphonylureas versus meglitinide, Outcome 14 Retinal photocoagulation.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 14 Retinal photocoagulation.

14.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

15 Change in fasting blood glucose from baseline (mmol/L) Show forest plot

10

2329

Mean Difference (IV, Random, 95% CI)

‐0.21 [‐0.45, 0.03]
Analysis 7.15
Comparison 7 Sulphonylureas versus meglitinide, Outcome 15 Change in fasting blood glucose from baseline (mmol/L).

Comparison 7 Sulphonylureas versus meglitinide, Outcome 15 Change in fasting blood glucose from baseline (mmol/L).

15.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

15.2 Second‐generation SU

9

2205

Mean Difference (IV, Random, 95% CI)

‐0.27 [‐0.51, ‐0.02]

15.3 Third‐generation SU

1

124

Mean Difference (IV, Random, 95% CI)

0.20 [‐0.22, 0.62]

16 Change in HbA1c from baseline (%) Show forest plot

10

2345

Mean Difference (IV, Random, 95% CI)

0.05 [‐0.09, 0.19]
Analysis 7.16
Comparison 7 Sulphonylureas versus meglitinide, Outcome 16 Change in HbA1c from baseline (%).

Comparison 7 Sulphonylureas versus meglitinide, Outcome 16 Change in HbA1c from baseline (%).

16.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

16.2 Second‐generation SU

9

2221

Mean Difference (IV, Random, 95% CI)

0.07 [‐0.08, 0.22]

16.3 Third‐generation SU

1

124

Mean Difference (IV, Random, 95% CI)

‐0.10 [‐0.40, 0.20]

17 Change in BMI from baseline (kg/m2) Show forest plot

3

333

Mean Difference (IV, Random, 95% CI)

‐0.05 [‐0.25, 0.14]
Analysis 7.17
Comparison 7 Sulphonylureas versus meglitinide, Outcome 17 Change in BMI from baseline (kg/m2).

Comparison 7 Sulphonylureas versus meglitinide, Outcome 17 Change in BMI from baseline (kg/m2).

17.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

17.2 Second‐generation SU

2

209

Mean Difference (IV, Random, 95% CI)

0.00 [‐0.19, 0.20]

17.3 Third‐generation SU

1

124

Mean Difference (IV, Random, 95% CI)

‐0.30 [‐0.66, 0.06]

18 Change in weight from baseline (kg) Show forest plot

5

1176

Mean Difference (IV, Random, 95% CI)

0.05 [‐0.40, 0.51]
Analysis 7.18
Comparison 7 Sulphonylureas versus meglitinide, Outcome 18 Change in weight from baseline (kg).

Comparison 7 Sulphonylureas versus meglitinide, Outcome 18 Change in weight from baseline (kg).

18.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

18.2 Second‐generation SU

4

1052

Mean Difference (IV, Random, 95% CI)

0.13 [‐0.50, 0.76]

18.3 Third‐generation SU

1

124

Mean Difference (IV, Random, 95% CI)

0.10 [‐1.77, 1.97]

19 Adverse events Show forest plot

5

1829

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.95, 1.06]
Analysis 7.19
Comparison 7 Sulphonylureas versus meglitinide, Outcome 19 Adverse events.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 19 Adverse events.

19.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19.2 Second‐generation SU

5

1829

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.95, 1.06]

19.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

20 Drop‐outs due to adverse events Show forest plot

8

2151

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.79, 1.33]
Analysis 7.20
Comparison 7 Sulphonylureas versus meglitinide, Outcome 20 Drop‐outs due to adverse events.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 20 Drop‐outs due to adverse events.

20.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

20.2 Second‐generation SU

7

2019

Risk Ratio (M‐H, Random, 95% CI)

1.01 [0.78, 1.32]

20.3 Third‐generation SU

1

132

Risk Ratio (M‐H, Random, 95% CI)

5.0 [0.24, 102.19]

21 Serious adverse events Show forest plot

5

1829

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.74, 1.39]
Analysis 7.21
Comparison 7 Sulphonylureas versus meglitinide, Outcome 21 Serious adverse events.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 21 Serious adverse events.

21.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

21.2 Second‐generation SU

5

1829

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.74, 1.39]

21.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

22 Mild hypoglycaemia Show forest plot

6

1863

Risk Ratio (M‐H, Random, 95% CI)

1.20 [0.96, 1.49]
Analysis 7.22
Comparison 7 Sulphonylureas versus meglitinide, Outcome 22 Mild hypoglycaemia.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 22 Mild hypoglycaemia.

22.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

22.2 Second‐generation SU

6

1863

Risk Ratio (M‐H, Random, 95% CI)

1.20 [0.96, 1.49]

22.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23 Moderate hypoglycaemia Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Analysis 7.23
Comparison 7 Sulphonylureas versus meglitinide, Outcome 23 Moderate hypoglycaemia.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 23 Moderate hypoglycaemia.

23.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24 Severe hypoglycaemia Show forest plot

6

1863

Risk Ratio (M‐H, Fixed, 95% CI)

2.87 [0.91, 8.99]
Analysis 7.24
Comparison 7 Sulphonylureas versus meglitinide, Outcome 24 Severe hypoglycaemia.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 24 Severe hypoglycaemia.

24.1 First‐generation SU

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

24.2 Second‐generation SU

6

1863

Risk Ratio (M‐H, Fixed, 95% CI)

2.87 [0.91, 8.99]

24.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

25 Cancer Show forest plot

2

290

Risk Ratio (M‐H, Random, 95% CI)

6.44 [0.27, 156.37]
Analysis 7.25
Comparison 7 Sulphonylureas versus meglitinide, Outcome 25 Cancer.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 25 Cancer.

25.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

25.2 Second‐generation SU

2

290

Risk Ratio (M‐H, Random, 95% CI)

6.44 [0.27, 156.37]

25.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

26 Intervention failure Show forest plot

5

1656

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.69, 1.35]
Analysis 7.26
Comparison 7 Sulphonylureas versus meglitinide, Outcome 26 Intervention failure.

Comparison 7 Sulphonylureas versus meglitinide, Outcome 26 Intervention failure.

26.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

26.2 Second‐generation SU

4

1524

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.69, 1.38]

26.3 Third‐generation SU

1

132

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.12, 3.86]
Open in table viewer
Comparison 8. Second‐generation sulphonylureas versus first‐generation sulphonylureas

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

0.90 [0.72, 1.11]
Analysis 8.1
Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 1 All‐cause mortality.

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 1 All‐cause mortality.

2 Cardiovascular mortality Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.72, 1.34]
Analysis 8.2
Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 2 Cardiovascular mortality.

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 2 Cardiovascular mortality.

3 Non‐fatal myocardial infarction Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

0.80 [0.55, 1.16]
Analysis 8.3
Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 3 Non‐fatal myocardial infarction.

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 3 Non‐fatal myocardial infarction.

4 Non‐fatal stroke Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

1.32 [0.80, 2.17]
Analysis 8.4
Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 4 Non‐fatal stroke.

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 4 Non‐fatal stroke.

5 Amputation of lower extremity Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

1.01 [0.29, 3.46]
Analysis 8.5
Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 5 Amputation of lower extremity.

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 5 Amputation of lower extremity.

6 Microvascular outcomes Show forest plot

1

1234

Odds Ratio (M‐H, Random, 95% CI)

0.70 [0.48, 1.03]
Analysis 8.6
Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 6 Microvascular outcomes.

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 6 Microvascular outcomes.

7 Retinal photocoagulation Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.56, 1.20]
Analysis 8.7
Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 7 Retinal photocoagulation.

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 7 Retinal photocoagulation.

8 Change in fasting blood glucose from baseline (mmol/L) Show forest plot

2

936

Mean Difference (IV, Random, 95% CI)

0.62 [0.31, 0.94]
Analysis 8.8
Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 8 Change in fasting blood glucose from baseline (mmol/L).

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 8 Change in fasting blood glucose from baseline (mmol/L).

9 Change in HbA1c from baseline (%) Show forest plot

2

1014

Mean Difference (IV, Random, 95% CI)

‐1.44 [‐4.48, 1.60]
Analysis 8.9
Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 9 Change in HbA1c from baseline (%).

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 9 Change in HbA1c from baseline (%).

10 Change in weight from baseline (kg) Show forest plot

2

1014

Mean Difference (IV, Random, 95% CI)

1.80 [‐0.63, 4.23]
Analysis 8.10
Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 10 Change in weight from baseline (kg).

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 10 Change in weight from baseline (kg).

11 Mild hypoglycaemia Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

2.51 [1.83, 3.42]
Analysis 8.11
Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 11 Mild hypoglycaemia.

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 11 Mild hypoglycaemia.

12 Severe hypoglycaemia Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

3.52 [0.73, 16.89]
Analysis 8.12
Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 12 Severe hypoglycaemia.

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 12 Severe hypoglycaemia.

13 Cancer Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

0.81 [0.50, 1.31]
Analysis 8.13
Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 13 Cancer.

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 13 Cancer.

14 Intervention failure Show forest plot

3

1364

Risk Ratio (M‐H, Random, 95% CI)

1.96 [0.67, 5.75]
Analysis 8.14
Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 14 Intervention failure.

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 14 Intervention failure.

Study flow diagram.N = number of references
Figuras y tablas -
Figure 1

Study flow diagram.

N = number of references

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'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figuras y tablas -
Figure 2

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

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'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 3

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

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Comparison 1 Sulphonylureas versus placebo, Outcome 1 All‐cause mortality.
Figuras y tablas -
Analysis 1.1

Comparison 1 Sulphonylureas versus placebo, Outcome 1 All‐cause mortality.

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Comparison 1 Sulphonylureas versus placebo, Outcome 2 All‐cause mortality; best‐worst case scenario.
Figuras y tablas -
Analysis 1.2

Comparison 1 Sulphonylureas versus placebo, Outcome 2 All‐cause mortality; best‐worst case scenario.

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Comparison 1 Sulphonylureas versus placebo, Outcome 3 All‐cause mortality; worst‐best case scenario.
Figuras y tablas -
Analysis 1.3

Comparison 1 Sulphonylureas versus placebo, Outcome 3 All‐cause mortality; worst‐best case scenario.

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Comparison 1 Sulphonylureas versus placebo, Outcome 4 Cardiovascular mortality.
Figuras y tablas -
Analysis 1.4

Comparison 1 Sulphonylureas versus placebo, Outcome 4 Cardiovascular mortality.

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Comparison 1 Sulphonylureas versus placebo, Outcome 5 Non‐fatal macrovascular outcomes.
Figuras y tablas -
Analysis 1.5

Comparison 1 Sulphonylureas versus placebo, Outcome 5 Non‐fatal macrovascular outcomes.

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Comparison 1 Sulphonylureas versus placebo, Outcome 6 Non‐fatal myocardial infarction.
Figuras y tablas -
Analysis 1.6

Comparison 1 Sulphonylureas versus placebo, Outcome 6 Non‐fatal myocardial infarction.

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Comparison 1 Sulphonylureas versus placebo, Outcome 7 Amputation of lower extremity.
Figuras y tablas -
Analysis 1.7

Comparison 1 Sulphonylureas versus placebo, Outcome 7 Amputation of lower extremity.

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Comparison 1 Sulphonylureas versus placebo, Outcome 8 Nephropathy.
Figuras y tablas -
Analysis 1.8

Comparison 1 Sulphonylureas versus placebo, Outcome 8 Nephropathy.

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Comparison 1 Sulphonylureas versus placebo, Outcome 9 Retinopathy.
Figuras y tablas -
Analysis 1.9

Comparison 1 Sulphonylureas versus placebo, Outcome 9 Retinopathy.

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Comparison 1 Sulphonylureas versus placebo, Outcome 10 Change in fasting blood glucose from baseline (mmol/L).
Figuras y tablas -
Analysis 1.10

Comparison 1 Sulphonylureas versus placebo, Outcome 10 Change in fasting blood glucose from baseline (mmol/L).

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Comparison 1 Sulphonylureas versus placebo, Outcome 11 Change in HbA1c from baseline (%).
Figuras y tablas -
Analysis 1.11

Comparison 1 Sulphonylureas versus placebo, Outcome 11 Change in HbA1c from baseline (%).

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Comparison 1 Sulphonylureas versus placebo, Outcome 12 Change in BMI from baseline (kg/m2).
Figuras y tablas -
Analysis 1.12

Comparison 1 Sulphonylureas versus placebo, Outcome 12 Change in BMI from baseline (kg/m2).

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Comparison 1 Sulphonylureas versus placebo, Outcome 13 Change in weight from baseline (kg).
Figuras y tablas -
Analysis 1.13

Comparison 1 Sulphonylureas versus placebo, Outcome 13 Change in weight from baseline (kg).

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Comparison 1 Sulphonylureas versus placebo, Outcome 14 Adverse events.
Figuras y tablas -
Analysis 1.14

Comparison 1 Sulphonylureas versus placebo, Outcome 14 Adverse events.

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Comparison 1 Sulphonylureas versus placebo, Outcome 15 Drop‐outs due to adverse events.
Figuras y tablas -
Analysis 1.15

Comparison 1 Sulphonylureas versus placebo, Outcome 15 Drop‐outs due to adverse events.

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Comparison 1 Sulphonylureas versus placebo, Outcome 16 Mild hypoglycaemia.
Figuras y tablas -
Analysis 1.16

Comparison 1 Sulphonylureas versus placebo, Outcome 16 Mild hypoglycaemia.

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Comparison 1 Sulphonylureas versus placebo, Outcome 17 Severe hypoglycaemia.
Figuras y tablas -
Analysis 1.17

Comparison 1 Sulphonylureas versus placebo, Outcome 17 Severe hypoglycaemia.

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Comparison 1 Sulphonylureas versus placebo, Outcome 18 Cancer.
Figuras y tablas -
Analysis 1.18

Comparison 1 Sulphonylureas versus placebo, Outcome 18 Cancer.

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Comparison 1 Sulphonylureas versus placebo, Outcome 19 Intervention failure.
Figuras y tablas -
Analysis 1.19

Comparison 1 Sulphonylureas versus placebo, Outcome 19 Intervention failure.

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Comparison 2 Sulphonylureas versus metformin, Outcome 1 All‐cause mortality.
Figuras y tablas -
Analysis 2.1

Comparison 2 Sulphonylureas versus metformin, Outcome 1 All‐cause mortality.

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Comparison 2 Sulphonylureas versus metformin, Outcome 2 All‐cause mortality; best‐worst case scenario.
Figuras y tablas -
Analysis 2.2

Comparison 2 Sulphonylureas versus metformin, Outcome 2 All‐cause mortality; best‐worst case scenario.

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Comparison 2 Sulphonylureas versus metformin, Outcome 3 All‐cause mortality; worst‐best case scenario.
Figuras y tablas -
Analysis 2.3

Comparison 2 Sulphonylureas versus metformin, Outcome 3 All‐cause mortality; worst‐best case scenario.

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Comparison 2 Sulphonylureas versus metformin, Outcome 4 Cardiovascular mortality.
Figuras y tablas -
Analysis 2.4

Comparison 2 Sulphonylureas versus metformin, Outcome 4 Cardiovascular mortality.

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Comparison 2 Sulphonylureas versus metformin, Outcome 5 Non‐fatal macrovascular outcomes.
Figuras y tablas -
Analysis 2.5

Comparison 2 Sulphonylureas versus metformin, Outcome 5 Non‐fatal macrovascular outcomes.

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Comparison 2 Sulphonylureas versus metformin, Outcome 6 Non‐fatal myocardial infarction.
Figuras y tablas -
Analysis 2.6

Comparison 2 Sulphonylureas versus metformin, Outcome 6 Non‐fatal myocardial infarction.

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Comparison 2 Sulphonylureas versus metformin, Outcome 7 Non‐fatal stroke.
Figuras y tablas -
Analysis 2.7

Comparison 2 Sulphonylureas versus metformin, Outcome 7 Non‐fatal stroke.

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Comparison 2 Sulphonylureas versus metformin, Outcome 8 Amputation of lower extremity.
Figuras y tablas -
Analysis 2.8

Comparison 2 Sulphonylureas versus metformin, Outcome 8 Amputation of lower extremity.

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Comparison 2 Sulphonylureas versus metformin, Outcome 9 Peripheral revascularisation.
Figuras y tablas -
Analysis 2.9

Comparison 2 Sulphonylureas versus metformin, Outcome 9 Peripheral revascularisation.

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Comparison 2 Sulphonylureas versus metformin, Outcome 10 Microvascular outcomes.
Figuras y tablas -
Analysis 2.10

Comparison 2 Sulphonylureas versus metformin, Outcome 10 Microvascular outcomes.

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Comparison 2 Sulphonylureas versus metformin, Outcome 11 Nephropathy.
Figuras y tablas -
Analysis 2.11

Comparison 2 Sulphonylureas versus metformin, Outcome 11 Nephropathy.

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Comparison 2 Sulphonylureas versus metformin, Outcome 12 Retinal photocoagulation.
Figuras y tablas -
Analysis 2.12

Comparison 2 Sulphonylureas versus metformin, Outcome 12 Retinal photocoagulation.

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Comparison 2 Sulphonylureas versus metformin, Outcome 13 Change in fasting blood glucose from baseline (mmol/L).
Figuras y tablas -
Analysis 2.13

Comparison 2 Sulphonylureas versus metformin, Outcome 13 Change in fasting blood glucose from baseline (mmol/L).

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Comparison 2 Sulphonylureas versus metformin, Outcome 14 Change in HbA1c from baseline (%).
Figuras y tablas -
Analysis 2.14

Comparison 2 Sulphonylureas versus metformin, Outcome 14 Change in HbA1c from baseline (%).

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Comparison 2 Sulphonylureas versus metformin, Outcome 15 Change in BMI from baseline (kg/m2).
Figuras y tablas -
Analysis 2.15

Comparison 2 Sulphonylureas versus metformin, Outcome 15 Change in BMI from baseline (kg/m2).

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Comparison 2 Sulphonylureas versus metformin, Outcome 16 Change in weight from baseline (kg).
Figuras y tablas -
Analysis 2.16

Comparison 2 Sulphonylureas versus metformin, Outcome 16 Change in weight from baseline (kg).

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Comparison 2 Sulphonylureas versus metformin, Outcome 17 Adverse events.
Figuras y tablas -
Analysis 2.17

Comparison 2 Sulphonylureas versus metformin, Outcome 17 Adverse events.

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Comparison 2 Sulphonylureas versus metformin, Outcome 18 Serious adverse events.
Figuras y tablas -
Analysis 2.18

Comparison 2 Sulphonylureas versus metformin, Outcome 18 Serious adverse events.

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Comparison 2 Sulphonylureas versus metformin, Outcome 19 Drop‐outs due to adverse events.
Figuras y tablas -
Analysis 2.19

Comparison 2 Sulphonylureas versus metformin, Outcome 19 Drop‐outs due to adverse events.

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Comparison 2 Sulphonylureas versus metformin, Outcome 20 Mild hypoglycaemia.
Figuras y tablas -
Analysis 2.20

Comparison 2 Sulphonylureas versus metformin, Outcome 20 Mild hypoglycaemia.

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Comparison 2 Sulphonylureas versus metformin, Outcome 21 Moderate hypoglycaemia.
Figuras y tablas -
Analysis 2.21

Comparison 2 Sulphonylureas versus metformin, Outcome 21 Moderate hypoglycaemia.

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Comparison 2 Sulphonylureas versus metformin, Outcome 22 Severe hypoglycaemia.
Figuras y tablas -
Analysis 2.22

Comparison 2 Sulphonylureas versus metformin, Outcome 22 Severe hypoglycaemia.

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Comparison 2 Sulphonylureas versus metformin, Outcome 23 Cancer.
Figuras y tablas -
Analysis 2.23

Comparison 2 Sulphonylureas versus metformin, Outcome 23 Cancer.

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Comparison 2 Sulphonylureas versus metformin, Outcome 24 Intervention failure.
Figuras y tablas -
Analysis 2.24

Comparison 2 Sulphonylureas versus metformin, Outcome 24 Intervention failure.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 1 All‐cause mortality.
Figuras y tablas -
Analysis 3.1

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 1 All‐cause mortality.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 2 All‐cause mortality; best‐worst case scenario.
Figuras y tablas -
Analysis 3.2

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 2 All‐cause mortality; best‐worst case scenario.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 3 All‐cause mortality; worst‐best case scenario.
Figuras y tablas -
Analysis 3.3

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 3 All‐cause mortality; worst‐best case scenario.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 4 Cardiovascular mortality.
Figuras y tablas -
Analysis 3.4

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 4 Cardiovascular mortality.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 5 Non‐fatal macrovascular outcomes.
Figuras y tablas -
Analysis 3.5

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 5 Non‐fatal macrovascular outcomes.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 6 Non‐fatal myocardial infarction.
Figuras y tablas -
Analysis 3.6

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 6 Non‐fatal myocardial infarction.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 7 Non‐fatal stroke.
Figuras y tablas -
Analysis 3.7

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 7 Non‐fatal stroke.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 8 Amputation of lower extremity.
Figuras y tablas -
Analysis 3.8

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 8 Amputation of lower extremity.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 9 Cardial revascularisation.
Figuras y tablas -
Analysis 3.9

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 9 Cardial revascularisation.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 10 Peripheral revascularisation.
Figuras y tablas -
Analysis 3.10

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 10 Peripheral revascularisation.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 11 Microvascular outcomes.
Figuras y tablas -
Analysis 3.11

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 11 Microvascular outcomes.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 12 Nephropathy.
Figuras y tablas -
Analysis 3.12

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 12 Nephropathy.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 13 Retinopathy.
Figuras y tablas -
Analysis 3.13

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 13 Retinopathy.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 14 Retinal photocoagulation.
Figuras y tablas -
Analysis 3.14

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 14 Retinal photocoagulation.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 15 Change in fasting blood glucose from baseline (mmol/L).
Figuras y tablas -
Analysis 3.15

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 15 Change in fasting blood glucose from baseline (mmol/L).

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 16 Change in HbA1c from baseline (%).
Figuras y tablas -
Analysis 3.16

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 16 Change in HbA1c from baseline (%).

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 17 Change in BMI from baseline (kg/m2).
Figuras y tablas -
Analysis 3.17

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 17 Change in BMI from baseline (kg/m2).

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 18 Change in weight from baseline (kg).
Figuras y tablas -
Analysis 3.18

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 18 Change in weight from baseline (kg).

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 19 Adverse events.
Figuras y tablas -
Analysis 3.19

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 19 Adverse events.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 20 Serious adverse events.
Figuras y tablas -
Analysis 3.20

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 20 Serious adverse events.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 21 Drop‐outs due to adverse events.
Figuras y tablas -
Analysis 3.21

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 21 Drop‐outs due to adverse events.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 22 Mild hypoglycaemia.
Figuras y tablas -
Analysis 3.22

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 22 Mild hypoglycaemia.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 23 Moderate hypoglycaemia.
Figuras y tablas -
Analysis 3.23

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 23 Moderate hypoglycaemia.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 24 Severe hypoglycaemia.
Figuras y tablas -
Analysis 3.24

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 24 Severe hypoglycaemia.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 25 Cancer.
Figuras y tablas -
Analysis 3.25

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 25 Cancer.

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Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 26 Intervention failure.
Figuras y tablas -
Analysis 3.26

Comparison 3 Sulphonylureas versus thiazolidinediones, Outcome 26 Intervention failure.

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Comparison 4 Sulphonylureas versus insulin, Outcome 1 All‐cause mortality.
Figuras y tablas -
Analysis 4.1

Comparison 4 Sulphonylureas versus insulin, Outcome 1 All‐cause mortality.

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Comparison 4 Sulphonylureas versus insulin, Outcome 2 All‐cause mortality; best‐worst case scenario.
Figuras y tablas -
Analysis 4.2

Comparison 4 Sulphonylureas versus insulin, Outcome 2 All‐cause mortality; best‐worst case scenario.

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Comparison 4 Sulphonylureas versus insulin, Outcome 3 All‐cause mortality; worst‐best case scenario.
Figuras y tablas -
Analysis 4.3

Comparison 4 Sulphonylureas versus insulin, Outcome 3 All‐cause mortality; worst‐best case scenario.

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Comparison 4 Sulphonylureas versus insulin, Outcome 4 Cardiovascular mortality.
Figuras y tablas -
Analysis 4.4

Comparison 4 Sulphonylureas versus insulin, Outcome 4 Cardiovascular mortality.

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Comparison 4 Sulphonylureas versus insulin, Outcome 5 Non‐fatal myocardial infarction.
Figuras y tablas -
Analysis 4.5

Comparison 4 Sulphonylureas versus insulin, Outcome 5 Non‐fatal myocardial infarction.

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Comparison 4 Sulphonylureas versus insulin, Outcome 6 Non‐fatal stroke.
Figuras y tablas -
Analysis 4.6

Comparison 4 Sulphonylureas versus insulin, Outcome 6 Non‐fatal stroke.

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Comparison 4 Sulphonylureas versus insulin, Outcome 7 Amputation of lower extremity.
Figuras y tablas -
Analysis 4.7

Comparison 4 Sulphonylureas versus insulin, Outcome 7 Amputation of lower extremity.

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Comparison 4 Sulphonylureas versus insulin, Outcome 8 Microvascular outcomes.
Figuras y tablas -
Analysis 4.8

Comparison 4 Sulphonylureas versus insulin, Outcome 8 Microvascular outcomes.

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Comparison 4 Sulphonylureas versus insulin, Outcome 9 Nephropathy.
Figuras y tablas -
Analysis 4.9

Comparison 4 Sulphonylureas versus insulin, Outcome 9 Nephropathy.

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Comparison 4 Sulphonylureas versus insulin, Outcome 10 Retinopathy.
Figuras y tablas -
Analysis 4.10

Comparison 4 Sulphonylureas versus insulin, Outcome 10 Retinopathy.

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Comparison 4 Sulphonylureas versus insulin, Outcome 11 Retinal photocoagulation.
Figuras y tablas -
Analysis 4.11

Comparison 4 Sulphonylureas versus insulin, Outcome 11 Retinal photocoagulation.

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Comparison 4 Sulphonylureas versus insulin, Outcome 12 Change in fasting blood glucose from baseline (mmol/L).
Figuras y tablas -
Analysis 4.12

Comparison 4 Sulphonylureas versus insulin, Outcome 12 Change in fasting blood glucose from baseline (mmol/L).

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Comparison 4 Sulphonylureas versus insulin, Outcome 13 Change in HbA1c from baseline (%).
Figuras y tablas -
Analysis 4.13

Comparison 4 Sulphonylureas versus insulin, Outcome 13 Change in HbA1c from baseline (%).

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Comparison 4 Sulphonylureas versus insulin, Outcome 14 Change in BMI from baseline (kg/m2).
Figuras y tablas -
Analysis 4.14

Comparison 4 Sulphonylureas versus insulin, Outcome 14 Change in BMI from baseline (kg/m2).

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Comparison 4 Sulphonylureas versus insulin, Outcome 15 Change in weight from baseline (kg).
Figuras y tablas -
Analysis 4.15

Comparison 4 Sulphonylureas versus insulin, Outcome 15 Change in weight from baseline (kg).

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Comparison 4 Sulphonylureas versus insulin, Outcome 16 Adverse events.
Figuras y tablas -
Analysis 4.16

Comparison 4 Sulphonylureas versus insulin, Outcome 16 Adverse events.

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Comparison 4 Sulphonylureas versus insulin, Outcome 17 Drop‐outs due to adverse events.
Figuras y tablas -
Analysis 4.17

Comparison 4 Sulphonylureas versus insulin, Outcome 17 Drop‐outs due to adverse events.

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Comparison 4 Sulphonylureas versus insulin, Outcome 18 Mild hypoglycaemia.
Figuras y tablas -
Analysis 4.18

Comparison 4 Sulphonylureas versus insulin, Outcome 18 Mild hypoglycaemia.

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Comparison 4 Sulphonylureas versus insulin, Outcome 19 Severe hypoglycaemia.
Figuras y tablas -
Analysis 4.19

Comparison 4 Sulphonylureas versus insulin, Outcome 19 Severe hypoglycaemia.

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Comparison 4 Sulphonylureas versus insulin, Outcome 20 Cancer.
Figuras y tablas -
Analysis 4.20

Comparison 4 Sulphonylureas versus insulin, Outcome 20 Cancer.

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Comparison 4 Sulphonylureas versus insulin, Outcome 21 Intervention failure.
Figuras y tablas -
Analysis 4.21

Comparison 4 Sulphonylureas versus insulin, Outcome 21 Intervention failure.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 1 All‐cause mortality.
Figuras y tablas -
Analysis 5.1

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 1 All‐cause mortality.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 2 All‐cause mortality; best‐worst case scenario.
Figuras y tablas -
Analysis 5.2

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 2 All‐cause mortality; best‐worst case scenario.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 3 All‐cause mortality; worst‐best case scenario.
Figuras y tablas -
Analysis 5.3

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 3 All‐cause mortality; worst‐best case scenario.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 4 Cardiovascular mortality.
Figuras y tablas -
Analysis 5.4

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 4 Cardiovascular mortality.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 5 Non‐fatal macrovascular outcomes.
Figuras y tablas -
Analysis 5.5

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 5 Non‐fatal macrovascular outcomes.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 6 Non‐fatal myocardial infarction.
Figuras y tablas -
Analysis 5.6

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 6 Non‐fatal myocardial infarction.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 7 Non‐fatal stroke.
Figuras y tablas -
Analysis 5.7

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 7 Non‐fatal stroke.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 8 Amputation of lower extremity.
Figuras y tablas -
Analysis 5.8

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 8 Amputation of lower extremity.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 9 Cardial revascularisation.
Figuras y tablas -
Analysis 5.9

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 9 Cardial revascularisation.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 10 Peripheral revascularisation.
Figuras y tablas -
Analysis 5.10

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 10 Peripheral revascularisation.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 11 Microvascular outcomes.
Figuras y tablas -
Analysis 5.11

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 11 Microvascular outcomes.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 12 Nephropathy.
Figuras y tablas -
Analysis 5.12

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 12 Nephropathy.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 13 Retinopathy.
Figuras y tablas -
Analysis 5.13

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 13 Retinopathy.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 14 Retinal photocoagulation.
Figuras y tablas -
Analysis 5.14

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 14 Retinal photocoagulation.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 15 Change in fasting blood glucose from baseline (mmol/L).
Figuras y tablas -
Analysis 5.15

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 15 Change in fasting blood glucose from baseline (mmol/L).

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 16 Change in HbA1c from baseline (%).
Figuras y tablas -
Analysis 5.16

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 16 Change in HbA1c from baseline (%).

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 17 Change in BMI from baseline (kg/m2).
Figuras y tablas -
Analysis 5.17

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 17 Change in BMI from baseline (kg/m2).

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 18 Change in weight from baseline (kg).
Figuras y tablas -
Analysis 5.18

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 18 Change in weight from baseline (kg).

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 19 Adverse events.
Figuras y tablas -
Analysis 5.19

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 19 Adverse events.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 20 Serious adverse events.
Figuras y tablas -
Analysis 5.20

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 20 Serious adverse events.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 21 Drop‐outs due to adverse events.
Figuras y tablas -
Analysis 5.21

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 21 Drop‐outs due to adverse events.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 22 Mild hypoglycaemia.
Figuras y tablas -
Analysis 5.22

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 22 Mild hypoglycaemia.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 23 Moderate hypoglycaemia.
Figuras y tablas -
Analysis 5.23

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 23 Moderate hypoglycaemia.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 24 Severe hypoglycaemia.
Figuras y tablas -
Analysis 5.24

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 24 Severe hypoglycaemia.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 25 Cancer.
Figuras y tablas -
Analysis 5.25

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 25 Cancer.

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Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 26 Intervention failure.
Figuras y tablas -
Analysis 5.26

Comparison 5 Sulphonylureas versus alpha‐glucosidase inhibitors, Outcome 26 Intervention failure.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 1 All‐cause mortality.
Figuras y tablas -
Analysis 6.1

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 1 All‐cause mortality.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 2 All‐cause mortality; best‐worst case scenario.
Figuras y tablas -
Analysis 6.2

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 2 All‐cause mortality; best‐worst case scenario.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 3 All‐cause mortality; worst‐best case scenario.
Figuras y tablas -
Analysis 6.3

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 3 All‐cause mortality; worst‐best case scenario.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 4 Cardiovascular mortality.
Figuras y tablas -
Analysis 6.4

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 4 Cardiovascular mortality.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 5 Non‐fatal macrovascular outcomes.
Figuras y tablas -
Analysis 6.5

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 5 Non‐fatal macrovascular outcomes.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 6 Non‐fatal myocardial infarction.
Figuras y tablas -
Analysis 6.6

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 6 Non‐fatal myocardial infarction.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 7 Non‐fatal stroke.
Figuras y tablas -
Analysis 6.7

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 7 Non‐fatal stroke.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 8 Amputation of lower extremity.
Figuras y tablas -
Analysis 6.8

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 8 Amputation of lower extremity.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 9 Cardial revascularisation.
Figuras y tablas -
Analysis 6.9

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 9 Cardial revascularisation.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 10 Peripheral revascularisation.
Figuras y tablas -
Analysis 6.10

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 10 Peripheral revascularisation.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 11 Microvascular outcomes.
Figuras y tablas -
Analysis 6.11

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 11 Microvascular outcomes.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 12 Nephropathy.
Figuras y tablas -
Analysis 6.12

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 12 Nephropathy.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 13 Retinopathy.
Figuras y tablas -
Analysis 6.13

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 13 Retinopathy.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 14 Retinal photocoagulation.
Figuras y tablas -
Analysis 6.14

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 14 Retinal photocoagulation.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 15 Change in fasting blood glucose from baseline (mmol/L).
Figuras y tablas -
Analysis 6.15

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 15 Change in fasting blood glucose from baseline (mmol/L).

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 16 Change in HbA1c from baseline (%).
Figuras y tablas -
Analysis 6.16

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 16 Change in HbA1c from baseline (%).

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 17 Change in BMI from baseline (kg/m2).
Figuras y tablas -
Analysis 6.17

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 17 Change in BMI from baseline (kg/m2).

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 18 Change in weight from baseline (kg).
Figuras y tablas -
Analysis 6.18

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 18 Change in weight from baseline (kg).

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 19 Adverse events.
Figuras y tablas -
Analysis 6.19

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 19 Adverse events.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 20 Serious adverse events.
Figuras y tablas -
Analysis 6.20

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 20 Serious adverse events.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 21 Drop‐outs due to adverse events.
Figuras y tablas -
Analysis 6.21

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 21 Drop‐outs due to adverse events.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 22 Mild hypoglycaemia.
Figuras y tablas -
Analysis 6.22

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 22 Mild hypoglycaemia.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 23 Severe hypoglycaemia.
Figuras y tablas -
Analysis 6.23

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 23 Severe hypoglycaemia.

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Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 24 Intervention failure.
Figuras y tablas -
Analysis 6.24

Comparison 6 Sulphonylureas versus incretin‐based intervention, Outcome 24 Intervention failure.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 1 All‐cause mortality.
Figuras y tablas -
Analysis 7.1

Comparison 7 Sulphonylureas versus meglitinide, Outcome 1 All‐cause mortality.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 2 All‐cause mortality; best‐worst case scenario.
Figuras y tablas -
Analysis 7.2

Comparison 7 Sulphonylureas versus meglitinide, Outcome 2 All‐cause mortality; best‐worst case scenario.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 3 All‐cause mortality; worst‐best case scenario.
Figuras y tablas -
Analysis 7.3

Comparison 7 Sulphonylureas versus meglitinide, Outcome 3 All‐cause mortality; worst‐best case scenario.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 4 Cardiovascular mortality.
Figuras y tablas -
Analysis 7.4

Comparison 7 Sulphonylureas versus meglitinide, Outcome 4 Cardiovascular mortality.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 5 Non‐fatal macrovascular outcomes.
Figuras y tablas -
Analysis 7.5

Comparison 7 Sulphonylureas versus meglitinide, Outcome 5 Non‐fatal macrovascular outcomes.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 6 Non‐fatal myocardial infarction.
Figuras y tablas -
Analysis 7.6

Comparison 7 Sulphonylureas versus meglitinide, Outcome 6 Non‐fatal myocardial infarction.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 7 Non‐fatal stroke.
Figuras y tablas -
Analysis 7.7

Comparison 7 Sulphonylureas versus meglitinide, Outcome 7 Non‐fatal stroke.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 8 Amputation of lower extremity.
Figuras y tablas -
Analysis 7.8

Comparison 7 Sulphonylureas versus meglitinide, Outcome 8 Amputation of lower extremity.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 9 Cardial revascularisation.
Figuras y tablas -
Analysis 7.9

Comparison 7 Sulphonylureas versus meglitinide, Outcome 9 Cardial revascularisation.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 10 Peripheral revascularisation.
Figuras y tablas -
Analysis 7.10

Comparison 7 Sulphonylureas versus meglitinide, Outcome 10 Peripheral revascularisation.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 11 Microvascular outcomes.
Figuras y tablas -
Analysis 7.11

Comparison 7 Sulphonylureas versus meglitinide, Outcome 11 Microvascular outcomes.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 12 Nephropathy.
Figuras y tablas -
Analysis 7.12

Comparison 7 Sulphonylureas versus meglitinide, Outcome 12 Nephropathy.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 13 Retinopathy.
Figuras y tablas -
Analysis 7.13

Comparison 7 Sulphonylureas versus meglitinide, Outcome 13 Retinopathy.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 14 Retinal photocoagulation.
Figuras y tablas -
Analysis 7.14

Comparison 7 Sulphonylureas versus meglitinide, Outcome 14 Retinal photocoagulation.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 15 Change in fasting blood glucose from baseline (mmol/L).
Figuras y tablas -
Analysis 7.15

Comparison 7 Sulphonylureas versus meglitinide, Outcome 15 Change in fasting blood glucose from baseline (mmol/L).

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 16 Change in HbA1c from baseline (%).
Figuras y tablas -
Analysis 7.16

Comparison 7 Sulphonylureas versus meglitinide, Outcome 16 Change in HbA1c from baseline (%).

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 17 Change in BMI from baseline (kg/m2).
Figuras y tablas -
Analysis 7.17

Comparison 7 Sulphonylureas versus meglitinide, Outcome 17 Change in BMI from baseline (kg/m2).

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 18 Change in weight from baseline (kg).
Figuras y tablas -
Analysis 7.18

Comparison 7 Sulphonylureas versus meglitinide, Outcome 18 Change in weight from baseline (kg).

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 19 Adverse events.
Figuras y tablas -
Analysis 7.19

Comparison 7 Sulphonylureas versus meglitinide, Outcome 19 Adverse events.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 20 Drop‐outs due to adverse events.
Figuras y tablas -
Analysis 7.20

Comparison 7 Sulphonylureas versus meglitinide, Outcome 20 Drop‐outs due to adverse events.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 21 Serious adverse events.
Figuras y tablas -
Analysis 7.21

Comparison 7 Sulphonylureas versus meglitinide, Outcome 21 Serious adverse events.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 22 Mild hypoglycaemia.
Figuras y tablas -
Analysis 7.22

Comparison 7 Sulphonylureas versus meglitinide, Outcome 22 Mild hypoglycaemia.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 23 Moderate hypoglycaemia.
Figuras y tablas -
Analysis 7.23

Comparison 7 Sulphonylureas versus meglitinide, Outcome 23 Moderate hypoglycaemia.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 24 Severe hypoglycaemia.
Figuras y tablas -
Analysis 7.24

Comparison 7 Sulphonylureas versus meglitinide, Outcome 24 Severe hypoglycaemia.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 25 Cancer.
Figuras y tablas -
Analysis 7.25

Comparison 7 Sulphonylureas versus meglitinide, Outcome 25 Cancer.

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Comparison 7 Sulphonylureas versus meglitinide, Outcome 26 Intervention failure.
Figuras y tablas -
Analysis 7.26

Comparison 7 Sulphonylureas versus meglitinide, Outcome 26 Intervention failure.

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Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 1 All‐cause mortality.
Figuras y tablas -
Analysis 8.1

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 1 All‐cause mortality.

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Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 2 Cardiovascular mortality.
Figuras y tablas -
Analysis 8.2

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 2 Cardiovascular mortality.

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Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 3 Non‐fatal myocardial infarction.
Figuras y tablas -
Analysis 8.3

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 3 Non‐fatal myocardial infarction.

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Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 4 Non‐fatal stroke.
Figuras y tablas -
Analysis 8.4

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 4 Non‐fatal stroke.

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Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 5 Amputation of lower extremity.
Figuras y tablas -
Analysis 8.5

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 5 Amputation of lower extremity.

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Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 6 Microvascular outcomes.
Figuras y tablas -
Analysis 8.6

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 6 Microvascular outcomes.

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Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 7 Retinal photocoagulation.
Figuras y tablas -
Analysis 8.7

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 7 Retinal photocoagulation.

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Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 8 Change in fasting blood glucose from baseline (mmol/L).
Figuras y tablas -
Analysis 8.8

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 8 Change in fasting blood glucose from baseline (mmol/L).

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Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 9 Change in HbA1c from baseline (%).
Figuras y tablas -
Analysis 8.9

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 9 Change in HbA1c from baseline (%).

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Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 10 Change in weight from baseline (kg).
Figuras y tablas -
Analysis 8.10

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 10 Change in weight from baseline (kg).

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Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 11 Mild hypoglycaemia.
Figuras y tablas -
Analysis 8.11

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 11 Mild hypoglycaemia.

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Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 12 Severe hypoglycaemia.
Figuras y tablas -
Analysis 8.12

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 12 Severe hypoglycaemia.

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Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 13 Cancer.
Figuras y tablas -
Analysis 8.13

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 13 Cancer.

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Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 14 Intervention failure.
Figuras y tablas -
Analysis 8.14

Comparison 8 Second‐generation sulphonylureas versus first‐generation sulphonylureas, Outcome 14 Intervention failure.

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Summary of findings for the main comparison. Summary of findings (first‐generation sulphonylureas)

First‐generation sulphonylureas compared with controls for type 2 diabetes mellitus

Patient or population: participants with type 2 diabetes mellitus

Settings: outpatients

Intervention: first‐generation sulphonylureas (acetohexamide, carbutamide, chlorpropamide, tolbutamide, tolazamide)

Comparison: placebo, active comparators

Outcomes

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

All‐cause mortality

a. Intervention vs placebo
[30 weeks to 4.75 years]

b. Intervention vs insulin
[4.75 years to 10.0 years]

a.RR 1.46 (0.87 to 2.45)

b. RR 1.18 (0.88 to 1.59)

a. 553 (2)

b. 1944 (2)

⊕⊕⊝⊝
lowa

a. Small sample size (1.5% of the diversity‐adjusted required information size)

b. Trial sequential analysis showed that 5.7% of the required information size to detect or reject a 10% RRR was accrued

Cardiovascular mortality

a. Intervention vs placebo
[30 weeks to 4.75 years]

b. Intervention vs insulin
[4.75 years to 10.0 years]

a.RR 2.63 (1.32 to 5.22)

b. RR 1.36 (0.88 to 1.48)

a. 553 (2)

b. 1944 (2)

⊕⊕⊝⊝
lowa

a. Small sample size (0.7% of the diversity‐adjusted required information size)

b. Trial sequential analysis showed that 1.1% of the required information size to detect or reject a 10% RRR was accrued

Non‐fatal macrovascular outcomes

1. Composite

2. Non‐fatal myocardial infarction

Intervention vs insulin
[4.75 years to 10.0 years]

1a. not estimable

2b. RR 1.08 (0.81 to 1.45)

1a. See comment

2b.1944 (2)

1a. See comment

2b. ⊕⊕⊝⊝
lowa

1a. No meta‐analysis possible

Microvascular outcomes

Not estimable

See comment

See comment

No meta‐analysis possible

Cancer

Intervention vs insulin
[4.75 years to 10.0 years]

RR 0.81 (0.29 to 2.27)

1944 (2)

⊕⊕⊝⊝
lowa

One study reported any cancer and the other death due to cancer

Adverse events

1. All adverse events
2. Drop‐outs due to adverse events

Intervention vs alpha‐glucosidase inhibitors
[30 weeks]

1. RR 0.63 (0.52 to 0.76)

2. RR 0.28 (0.12 to 0.67)

1. 246 (2)
1. 246 (2)

⊕⊕⊝⊝
lowa

Trial sequential analysis showed that firm evidence was not established

Health‐related quality of life

Not estimable

See comment

See comment

Not investigated

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

aDue to imprecision and results of trial sequential analysis.

RRR: relative risk reduction
Figuras y tablas -
Summary of findings for the main comparison. Summary of findings (first‐generation sulphonylureas)
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Summary of findings 2. Summary of findings (second‐generation sulphonylureas)

Second‐generation sulphonylureas compared with controls for type 2 diabetes mellitus

Patient or population: participants with type 2 diabetes mellitus

Settings: outpatients

Intervention: second‐generation sulphonylureas (glibenclamide or glyburide, glibornuride, gliclazide, glipizide)

Comparison: placebo, active comparators

Outcomes

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Comments

All‐cause mortality

a. Intervention vs metformin
[a. 24 weeks to 4 years]

b. Intervention vs thiazolidinediones
[b. 24 weeks to 4 years]

c. Intervention vs insulin
[c. 9 months to 10 years]

d. Intervention vs incretin‐based control
[d. 52 weeks to 104 weeks]

e. Intervention vs meglitinide

[e. 12 months to 17 months]

a. RR 0.98 (0.61 to 1.58)

b. RR 0.92 (0.60 to 1.41)

c. RR 0.96 (0.79 to 1.18)

d. RR 1.39 (0.52 to 3.68)

e. RR 1.44 (0.47 to 4.42)

a. 3528 (6)

b. 4955 (7)

c. 1642 (4)

d. 1503 (2)

e. 2038 (7)

⊕⊕⊝⊝
lowa

a. Trial sequential analysis showed that 2.3% of the required information size to detect or reject a 10% RRR was accrued.

b. Results of the random‐effects model. Trial sequential analysis showed that 2.5% of the required information size to detect or reject a 10% RRR was accrued.

c. Trial sequential analysis showed that 12.8% of the required information size to detect or reject a 10% RRR was accrued.

d. Trial sequential analysis showed that 0.5% of the required information size to detect or reject a 10% RRR was accrued.

e. Trial sequential analysis showed that only a minor fraction of the required information size to detect or reject a 10% RRR was accrued.

Cardiovascular mortality

a. Intervention vs metformin
[a. 24 weeks to 4 years]

b. Intervention vs thiazolidinediones
[b. 24 weeks to 4 years]

c. Intervention vs insulin
[c. 9 months to 10 years]

d. Intervention vs meglitinide

[d. 12 months to 17 months]

a. RR 1.47 (0.54 to 4.01)

b. RR 1.30 (0.55 to 3.07)

c. RR 0.96 (0.73 to 1.28)

d. RR 0.97 (0.27 to 3.53)

a. 3528 (6)

b. 4955 (7)

c. 1642 (4)

d. 2038 (7)

⊕⊕⊝⊝
lowa

a. Trial sequential analysis showed that 2.7% of the required information size to detect or reject a 10% RRR was accrued.

b. Trial sequential analysis showed that 0.3% of the required information size to detect or reject a 10% RRR was accrued.

c. Trial sequential analysis showed that 6.6% of the required information size to detect or reject a 10% RRR was accrued.

d. Trial sequential analysis showed that only a minor fraction of the required information size to detect or reject a 10% RRR was accrued.

Non‐fatal macrovascular outcomes
1. Composite

a. Intervention vs metformin
[1a. 6 months to 4 years]

b. Intervention vs thiazolidinediones

[1b. 52 weeks to 4 years]

c. Intervention vs meglitinide

[1c. 12 months to 15 months]
2. Non‐fatal myocardial infarction

a. Intervention vs metformin
[2a. 24 weeks to 4 years]

b. Intervention vs thiazolidinediones

[2b. 24 weeks to 4 years]

c. Intervention vs meglitinide

[2c. 12 months to 17 months]

1a. RR 0.67 (0.48 to 0.93)

1b. RR 0.91 (0.62 to 1.33)

1c. RR 0.50 (0.20 to 1.20)

2a.RR 1.02 (0.37 to 2.85)

2b. RR 0.68 (0.41 to 1.14)

2c. RR 1.03 (0.26 to 4.08)

1a. 3018 (3)

1b. 4600 (6)

1c. 866 (3)

2a. 3061 (4)

2b. 4956 (7)

2c. 726 (3)

⊕⊕⊝⊝
lowa

1a. Non‐fatal macrovascular outcomes as a composite outcome were not reported in the way we predefined to assess this outcome. Trial sequential analysis showed that 5% of the required information size to detect or reject a 10% RRR was accrued.

1c. The definition of non‐fatal macrovascular outcomes was heterogenous.

Microvascular outcomes

Not estimable

See comment

See comment

No meta‐analysis possible

Adverse events

1. All adverse events
2. Drop‐outs due to adverse events
3. Severe hypoglycaemia

a. Intervention vs placebo
[1a. 24 weeks]
[2a. 24 weeks to 56 weeks]

b. Intervention vs metformin
[1b. 6 months to 4 years]
[2b. 24 weeks to 4 years]

[3b. 24 weeks to 10.4 years]

c. Intervention vs thiazolidinediones
[1c. 6 months to 4 years]
[2c. 24 weeks to 4 years ]

[3c. 6 months to 4 years]

d. Intervention vs alpha‐glucosidase inhibitors

[1d. 24 weeks to 12 months]
[2d. 24 weeks to 12 months]

e. Intervention vs incretin‐based control
[2e. 52 weeks to 104 weeks]

f. Intervention vs meglitinides
[1f. 14 months to 17 months]
[2f. 12 months to 17 months]

[3f. 14 months to 17 months]

1a. RR 0.91 (0.51 to 1.62)

1b. RR 0.99 (0.97 to 1.01)

1c. RR 0.99 (0.97 to 1.01)

1d. RR 0.64 (0.39 to 1.03)

1f. RR 1.0 (0.95 to 1.06)

2a. RR 0.62 (0.24 to 1.57)

2b.RR 1.19 (0.99 to 1.42)

2c. RR 1.15 (0.98 to 1.36)

2d. RR 0.48 (0.24 to 0.96)

2e. RR 1.00 (0.67 to 1.50)

2f. RR 1.01 (0.78 to 1.32)

3b. RR 5.64 (1.22 to 26.00)

3c. RR 6.11 (1.57 to 23.79)

3f. RR 2.17 (0.53 to 8.91)

1a. 202 (2)

1b. 3042 (2)

1c. 6491 (10)

1d. 646 (8)

1f. 1829 (5)

2a. 510 (5)

2b. 3567 (7)

2c. 7433 (15)

2d. 970 (9)

2e. 1503 (2)

2f. 2019 (7)

3b. 3637 (4)

3c. 5669 (6)

3f. 1863 (6)

⊕⊕⊝⊝
lowa

1d. Results of the random‐effects model. Fixed‐effect model: RR 0.67 (0.52 to 0.86)

2c. Results of the random‐effects model. Fixed‐effect model: RR 1.17 (1.01 to 1.35)

2d. Trial sequential analysis showed that only a minor fraction of the required information size to confirm or reject a 10% RRR was accrued

3b. Trial sequential analysis showed that only 0.1% of the required information size was accrued

3c. Trial sequential analysis showed that a minor fraction of the required information size was accrued

Cancer

a. Intervention vs thiazolidinediones
[52 weeks to 4 years]

b. Intervention vs insulin
[6 years to 10 years]

a. RR 1.02 (0.72 to 1.45)

b. RR 0.95 (0.61 to 1.49)

a. 4192 (6)

b. 1575 (2)

⊕⊕⊝⊝
lowa

Health‐related quality of life

a. Intervention vs thiazolidinediones
[12 months]

b. Intervention vs insulin
[6 years]

c. Intervention vs alpha‐glucosidase inhibitors
[12 months]

Not estimable

a. 35 (1)

b. 49 (1)

c. 35 (1)

⊕⊝⊝⊝
very lowb

a. Inadequately reported, no scale provided

b. Authors used short‐form 36 (SF 36), but did not find any significant differences between the interventions

c. Inadequately reported, no scale provided

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

aDue to imprecision and results of trial sequential analysis.

bDue to small sample size and risk of bias.

RRR: relative risk reduction
Figuras y tablas -
Summary of findings 2. Summary of findings (second‐generation sulphonylureas)
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Summary of findings 3. Summary of findings (third‐generation sulphonylureas)

Third‐generation sulphonylureas compared with controls for type 2 diabetes mellitus

Patient or population: participants with type 2 diabetes mellitus

Settings: outpatients

Intervention: third‐generation sulphonylureas (gliclazide modified release (MR), glimepiride, glipizide gastrointestinal therapeutic system (GITS))

Comparison: active comparators

Outcomes

Relative effect
(95% CI)

No of Participants
(studies)

Quality of the evidence
(GRADE)

Comments

All‐cause mortality

Not estimable

See comment

See comment

No meta‐analysis possible

Cardiovascular mortality

Not estimable

See comment

See comment

No meta‐analysis possible

Macrovascular outcomes

Not estimable

See comment

See comment

No meta‐analysis possible

Microvascular outcomes

Not estimable

See comment

See comment

No meta‐analysis possible

Adverse events

1. All adverse events
2. Drop‐outs due to adverse events

Interventions vs thiazolidinediones

[1. 6 months to 12 months]

[2. 24 weeks to 52 weeks]

1. RR 0.88 (0.78 to 0.99)

2. RR 0.54 (0.15 to 1.97)

1. 510 (3)

2. 423 (2)

⊕⊕⊝⊝
lowa

1. Trial sequential analysis showed that firm evidence was not established

Cancer

Not estimable

See comment

See comment

No meta‐analysis possible

Health‐related quality of life

Not estimable

See comment

See comment

No meta‐analysis possible

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

aDue to imprecision/small sample size and results of trial sequential analysis.

RRR: relative risk reduction
Figuras y tablas -
Summary of findings 3. Summary of findings (third‐generation sulphonylureas)
Ir a la tabla de la revisión
Table 1. Overview of study populations

Characteristic

Study ID

Intervention(s) and control(s)

[N] screened

[N] randomised

[N] safety

[N] lost to follow‐up (mortality)

[N] finishing study

[%] of randomised participants finishing study

Abbatecola 2006

I1: glibenclamide

C1: repaglinide

‐

I1: 79

C1: 77

T: 156

I1: 73

C1: 74

T: 147

‐

I1: 63

C1: 65

T: 128

I1: 80

C1: 84

T: 82

ADOPT 2006

I1: glibenclamide

C1: rosiglitazone

C2: metformin

6676

I1: 1447

C1: 1458

C2: 1455

T: 4360

I1: 1441

C1: 1456

C2: 1455

T: 4351

‐

I1: 807

C1: 917

C2: 903

T: 2627

I1: 56

C1: 63

C2: 62

T: 60

AGEE/DCD/046/UK

I1:glibenclamide

C1: repaglinide

313

I1: 86

C1: 178

T: 264

I1: 85

C1: 178

T: 264

‐

I1: 57

C1: 111

T: 168

I1:66

C1: 62

T: 64

AGEE/DCD/047/B/F/I

I1: gliclazide

C1: repaglinide

337

I1: 99

C1: 206

T: 305

I1: 99

C1: 206

T: 305

‐

I1: 68

C1: 138

T: 206

I1: 69

C1: 67

T: 68

Alvarsson 2010

I1: glibenclamide

C1: insulin

56

I1: 26

C1: 23

T: 49

‐

I1: 7

C1: 5

T: 12

I1: 18

C1: 16

T: 34

I1: 69

C1: 70

T: 70

APPROACH 2010 a

I1: glipizide

C1: rosiglitazone

1147

I1: 339

C1: 333

T: 672

I1: 337

C1: 331

T: 668

I1: 22

C1: 17

T: 39

I1: 264

C1: 259

T: 523

I1: 78

C1: 78

T: 78

Birkeland 1994

I1: glibenclamide

I2: glipizide

C1: placebo

‐

I1: 15

I2: 15

C1: 16

T: 46

‐

I1: 0

I2: 0

C1: 0

T: 0

I1: 15

I2: 13

C1: 12

T: 40

I1: 100

I2: 87

C1: 75

T: 87

Birkeland 2002

I1: glibenclamide

C1: insulin

54

I1: 18

C1: 18

T: 36

‐

‐

‐

N/A

Campbell 1994

I1: glipizide

C1: metformin

50 (?)

I1: 24

C1: 24

T: 48

I1: 24

C1: 24

T: 48

I1: 0

C1: 0

T: 0

I1: 24

C1: 24

T: 48

I1: 100

C1: 100

T: 100

Charbonnel 2005 b

I1: gliclazide

C1: pioglitazone

2412

I1: 626

C1: 624

T: 1270

‐

I1: 4

C1: 4

T: 8

I1: 525

C1: 530

T: 1055

I1: ‐

C1: ‐

T: 83

Collier 1989

I1: gliclazide

C1: metformin

‐

I1: 12

C1: 12

T: 24

I1: 12

C1: 12

T: 24

‐

I1: 12

C1: 12

T: 24

I1: 100

C1: 100

T: 100

Coniff 1995

I1: tolbutamide

C1: acarbose

C2: placebo

‐

I1: 72

C1: 76

C2: 72

T: 220

I1: 71

C1: 74

C2: 72

T: 217

‐

‐

N/A

Dalzell 1986

I1: tolbutamide

C1: metformin

‐

I1: 15

C1: 18

T: 33

‐

‐

‐

N/A

DeFronzo 2005

I1: glibenclamide

C1: metformin

788

I1: 209

C1: 210

T: 419

‐

‐

I1: 174

C1: 157

T: 331

I1: 83

C1: 75

T: 79

Deng 2003

I1: glibenclamide

C1: Xiaoyaosan

160

I1: 80

C1: 80

T: 160

‐

‐

‐

N/A

Derosa 2003

I1: glimepiride

C1: repaglinide

‐

I1: 66

C1: 66

T: 132

I1: 66

C1: 66

T: 132

I1: 4

C1: 4

T: 8

I1: 62

C1: 62

T: 124

I1: 94

C1: 94

T: 94

Derosa 2004

I1: glimepiride

C1: metformin

‐

I1: 81

C1: 83

T: 164

I1: 81

C1: 83

T: 164

‐

I1: 73

C1: 75

T: 148

I1:90

C1: 90

T: 90

Diehl 1985

I1: chlorpropamide

C1: insulin

137

I1: 40

C1: 37

T: 77

‐

‐

I1: 30

C1: 28

T: 58

I1: 75

C1: 77

T: 75

Ebeling 2001

I1: glibenclamide

C1: pioglitazone

C2: placebo

‐

I1: 10

C1: 9

C2: 10

T: 29

‐

‐

‐

N/A

Esposito 2004

I1: glibenclamide

C1: repaglinide

210

I1: 87

C1: 88

T: 175

I1: 87

C1: 88

T: 175

I1: 7

C1: 7

T: 14

I1: 80

C1: 81

T: 161

I1: 92

C1: 92

T: 92

Feinböck 2003

I1: glibenclamide

C1: acarbose

‐

I1: 111

C1: 108

T: 219

I1: 93

C1: 59

T: 152

‐

I1: 93

C1: 59

T: 152

I1: 84

C1: 55

T: 69

Fineberg 1980 c

I1: glipizide

C1: tolbutamide

‐

I1: ‐

C1: ‐

T: 29

‐

‐

I1: 8

C1: 10

T: 18

I1: ‐

C1: ‐

T: 62

Foley 2009

I1: gliclazide

C1: vildagliptin

‐

I1: 546

C1: 546

T: 1092

I1: 402

C1: 409

T: 811

I1: 13

C1: 17

T: 30

I1: 402

C1: 409

T: 811

I1:74

C1: 75

T: 74

Forst 2003

I1: glibenclamide

C1: insulin

200

I1: 68

C1: 75

T: 143

I1: 68

C1: 75

T: 143

I1: 0

C1: 0

T: 0

I1: 68

C1: 75

T: 143

I1: 100

C1: 100

T: 100

Forst 2005

I1: glimepiride

C1: pioglitazone

192

I1: 87

C1: 92

T: 179

I1: 84

C1: 89

T: 173

I1: 3

C1: 3

T: 6

I1: 84

C1: 89

T: 173

I1:97

C1: 97

T: 97

Hanefeld 2005

I1: glibenclamide

C1: rosiglitazone 2 mg

C2: rosiglitazone 4 mg

‐

I1: 207

C1: 200

C2: 191

T: 598

‐

I1: 0

C1: 0

C2: 0

T: 0

I1: 173

C1: 153

C2: 158

T: 484

I1: 84

C1: 77

C2: 83

T: 81

Harrower 1985

I1: glipizide

I2: gliquidone

I3: gliclazide

I4: glibenclamide

C1: chlorpropamide

‐

I1: 24

I2: 22

I3: 22

I4: 23
C1: 21

T: 112

‐

I1: 4

I2: 3

I3: 2

I4: 4
C1: 3

T: 16

I1: 20

I2: 19

I3: 20

I4: 19
C1: 18

T: 96

I1: 83

I2: 86

I3: 91

I4: 83
C1: 86

T: 86

Hermann 1991 d

I1: glibenclamide

C1: metformin

‐

I1: ‐

C1: ‐

T: 25

I1: 10

C1: 12

T: 22

‐

I1: 10

C1: 12

T: 22

N/A

Hermann 1991a

I1: glibenclamide

C1: metformin

‐

I1: 34

C1: 38

T: 72

‐

I1: 0

C1: 0

T: 0

I1: 28

C1: 28

T: 56

I1: 82

C1: 74

T: 78

Hoffmann 1990

I1: glibenclamide

C1: acarbose

‐

I1: 47

C1: 48

T: 95

‐

‐

‐

N/A

Hoffmann 1994

I1: glibenclamide

C1: placebo

C2: acarbose

96

I1: 27

C1: 30

C2: 28

T: 85

‐

I1: 0

C1: 0

T: 0

I1: 27

C1: 30

C2: 28

T: 85

I1: 100

C1: 100

C2: 100

Hollander 1992

I1: glibenclamide

C1: insulin

‐

I1: 29

C1: 30

T: 59

‐

‐

‐

N/A

Jain 2006

I1: glibenclamide

C1: pioglitazone

‐

I1: 251

C1: 251

T: 502

‐

I1: 21

C1: 22

T: 43

I1: 128

C1: 134

T: 262

I1: 50

C1: 53

T: 52

Jibran 2006

I1: glibenclamide

C1: repaglinide

‐

I1: 50

C1: 50

T: 100

‐

‐

‐

N/A

Johnston 1997

I1: glibenclamide

C1: placebo

C2: miglitol 25 mg

C3: miglitol 50 mg

‐

I1: 104

C1: 101

C2: 104

C3: 102

T: 411

‐

‐

‐

N/A

Kaku 2011

I1: glibenclamide

C1: liraglutide

464

I1: 139

C1: 272

T: 411

I1: 132

C1: 268

T: 400

‐

I1: 110

C1: 225

T: 335

I1: 79

C1: 83

T: 82

Kamel 1997

I1: gliclazide

I2: glibenclamide

C1: acarbose

C2: metformin

C3: placebo

‐

I1: 9

I2: 8

C1: 10

C2: 6

C3: 10

T: 43

‐

‐

‐

N/A

Kanda 1998

I1: gliclazide

C1: acarbose

25

I1: 9

C1: 10

T: 19

‐

‐

I1: 9

C1: 10

T: 19

I1: 100

C1: 100

T: 100

Kovacevic 1997

I1: glibenclamide

C1: acarbose

C2: placebo

‐

I1: 34

C1: 34

C2: 34

T: 102

I1: 33

C1: 33

C2: 31

T: 97

‐

I1: 33

C1: 33

C2: 31

T: 97

I1: 97

C1: 97

C2: 91

T: 95

Lawrence 2004

I1: gliclazide

C1: metformin

C2: pioglitazone

67

I1: 22

C1: 21

C2: 21

T: 64

‐

I1: 0

C1: 0

C2: 0

T: 0

I1: 20

C1: 20

C2: 20

T: 60

I1: 91

C1: 95

C2: 95

T: 94

LEAD‐3 2006 e

I1: glimepiride

C1: liraglutide 1.2 mg

C2: liraglutide 1.8 mg

‐

I1: 248

C1: 251

C2: 247

T: 746

I1: 248

C1: 251

C2: 246

T: 745

‐

I1: 152

C1: 162

C2: 173

T: 487

I1: 61

C1: 65

C2: 70

T: 65

Madsbad 2001

I1: glipizide

C1: repaglinide

320

I1: 81

C1: 175

T: 256

I1: 81

C1: 175

T: 256

‐

I1: 58

C1: 140

T: 198

I1: 72

C1: 80

T: 77

Marbury 1999

I1: glibenclamide

C1: repaglinide

‐

I1: 193

C1: 383

T: 576

I1: 193

C1: 383

T: 576

‐

I1: 115

C1: 216

T: 331

I1: 60

C1: 56

T: 57

Memisogullari 2009

I1: gliclazide

C1: nothing

‐

I1: 26

C1: 30

T: 56

‐

I1:0

C1: 0

T: 0

‐

N/A

Nakamura 2004

I1: glibenclamide

C1: pioglitazone

C2: voglibose

‐

I1: 15

C1: 15

C2: 15

T: 45

I1: 15

C1: 15

C2: 15

T: 45

I1: 0

C1: 0

C2: 0

T: 0

I1: 15

C1: 15

C2: 15

T: 45

I1: 100

C1: 100

C2: 100

T: 100

Nakamura 2006

I1: glibenclamide

C1: pioglitazone

C2: voglibose

C3: nateglinide

78

I1: 18

C1: 17

C2: 17

C3: 16

T: 68

I1: 18

C1: 17

C2: 17

C3: 16

T: 68

I1: 0

C1: 0

C2: 0

C3: 0

T: 0

I1: 18

C1: 17

C2: 17

C3: 16

T: 68

I1: 100

C1: 100

C2: 100

C3: 100

T: 100

Nathan 1988

I1: glibenclamide

C1: insulin

‐

I1: 16

C1: 15

T: 31

I1: 16

C1: 15

T: 31

I1: 0

C1: 0

T: 0

I1: 16

C1: 15

T: 31

I1: 100

C1: 100

T: 100

Pagano 1995 f

I1: glibenclamide

C1: miglitol

‐

I1: 47

C1: 50

T: 100

I1: ‐

C1: ‐

T: 99

I1: ‐

C1: ‐

T: 3

I1: 47

C1: 49

T: 96

I1: ‐

C1: ‐

T: 96

Perriello 2007

I1: gliclazide

C1: pioglitazone

‐

I1: 137

C1: 146

T: 283

‐

‐

I1: 135

C1: 140

T: 275

I1: 99

C1: 96

T: 97

Rosenthal 2002

I1: glibenclamide

C1: acarbose

‐

I1: 37

C1: 39

T: 76

I1: 31

C1: 32

T: 63

‐

I1: 31

C1: 32

T: 63

I1: 84

C1: 82

T: 83

Salman 2001

I1: gliclazide

C1: acarbose

‐

I1: 35

C1: 33

T: 68

I1: 30

C1: 27

T: 57

‐

I1: 30

C1: 27

T: 57

I1: 86

C1: 82

T: 84

Segal 1997

I1: glibenclamide

C1: miglitol

C2: placebo

‐

I1: 69

C1: 67

C2: 65

T: 201

I1: 69

C1: 67

C2: 65

T: 201

I1: 11

C1: 12

C2: 6

T: 29

I1: 50

C1: 49

C2: 58

T: 157

I1: 72

C1: 73

C2: 89

T: 78

Shihara 2011

I1: glimepiride

C1: pioglitazone

238

I1: 95

C1: 96

T: 191

I1: 86

C1: 91

T: 177

‐

I1: 86

C1: 91

T: 177

I1: 91

C1: 95

T: 93

Spengler 1992 g

I1: glibenclamide

C1: acarbose

‐

I1: 36

C1: 36

T: 72

‐

‐

I1: 29

C1: 26

T: 55

I1: 81

C1: 72

T: 76

Sung 1999

I1: glibenclamide

C1: troglitazone

‐

I1: 12

C1: 10

T: 22

‐

‐

‐

N/A

Sutton 2002 h

I1: glibenclamide

C1: rosiglitazone

351

I1: 99

C1: 104

T: 203

I1: 99

C1: 104

T: 203

I1: 3

C1: 2

T: 5

I1: 65

C1: 64

T: 129

I1: 66

C1: 62

T: 64

Tan 2004

I1: glimepiride

C1: pioglitazone

584

I1: 123

C1: 121

T: 244

I1: 92

C1: 100

T: 192

I1: 11

C1: 6

T: 17

I1: 89

C1: 87

T: 176

I1: 72

C1: 72

T: 72

Tan 2004a

I1: glimepiride

C1: pioglitazone

‐

I1: 109

C1: 91

T: 200

I1: 109

C1: 91

T: 200

‐

I1: 68

C1: 55

T: 123

I1: 62

C1: 60

T: 62

Tan 2005 i

I1: gliclazide

C1: pioglitazone

2412

I1: 297

C1: 270

T: 567

‐

I1: 4

C1: 2

T: 6

I1: 127

C1: 147

T: 274

I1: 43

C1: 54

T: 48

Tang 2004

I1: glimepiride

C1: metformin

‐

I1: 33

C1: 29

T: 62

‐

‐

‐

N/A

Teramoto 2007

I1: glibenclamide

C1: pioglitazone

126

I1: 46

C1: 46
T: 92

I1: 41

C1: 39

T: 80

‐

I1: 41

C1: 39

T: 80

I1: 89

C1: 85

T: 86

Tessier 1999

I1: gliclazide

C1: metformin

‐

I1: 19

C1: 20

T: 39

‐

I1: 1

C1: 2

T: 3

I1: 18
C1: 18
T:36

I1: 94.7
C1: 90
T: 92.3

Tosi 2003

I1: glibenclamide

C1: metformin

‐

I1: 22

C1: 22

T: 44

‐

‐

I1: 20

C1: 19

T: 39

I1: 91

C1: 86

T: 89

UGDP 1970

I1: tolbutamide

C1: placebo

C1: insulin

‐

I1: 204

C1: 205

C2: 210

T: 619

I1: 75% on tolbutamide

C1: 75% on placebo

C2: ‐

T: ‐

‐

‐

N/A

UKPDS 1998 j

Study 1:

I1: chlorpropamide

I2: glibenclamide

I3: glipizide

C1: insulin

7616

I1: 788

I2: 615

I3: 170

C1: 1156

T: 2729

‐

‐

‐

N/A

UKPDS 34 1998

I1: chlorpropamide

I2: glibenclamide

C1: metformin

C2: insulin

4209

I1: 265

I2: 277

C1: 342

C2: 409

T: 1293

‐

I1: ‐

I2: ‐

C1: ‐

C2: ‐

T: 13

‐

N/A

van de Laar 2004

I1: tolbutamide

C1: acarbose

144

I1: 50

C1: 48

T: 98

I1: 48

C1: 48

T: 96

I1: 5

C1: 16

T: 21

I1: 43

C1: 32

T: 75

I1: 86

C1: 67

T: 77

Watanabe 2005

I1: glibenclamide

C1: pioglitazone

‐

I1: 15

C1: 15
T: 30

I1: 14

C1: 13
T: 27

I1: 1

C1: 2
T: 3

I1: 14

C1: 13
T: 27

I1: 93

C1: 87
T: 90

Wolffenbuttel 1989

I1: tolbutamide

C1: insulin

‐

I1: 6

C1: 7

T: 13

‐

‐

‐

N/A

Wolffenbuttel 1999

I1: glibenclamide

C1: repaglinide

491

I1: 140

C1: 288
T: 428

I1: 139

C1: 286
T: 425

‐

I1: 109

C1: 211

T: 320

I1: 78

C1: 74

T: 75

Yamanouchi 2005

I1: glimepiride

C1: pioglitazone

C2: metformin

‐

I1: 37

C1: 38

C2: 39

T: 114

‐

I1: 3

C1: 0

C2: 1

T: 4

I1: 34

C1: 35

C2: 37

T: 106

I1: 92

C1: 92

C2: 95

T: 93

Zhang 2005

I1: glipizide

C1: rosiglitazone 4 mg

C2: rosiglitazone 8 mg

45

I1: 8

C1: 8

C2: 8

T: 24

I1: 8

C1: 8

C2: 8

T: 24

I1: 0

C1: 0

C2: 0

T: 0

I1: 8

C1: 8

C2: 8

T: 24

I1: 100

C1: 100

C2: 100

T: 100

Totalk

I: any sulphonylurea

C: any comparator

I: 9707

C: 12,805

T:22,589

I: 4901

C: 6888

T:11,789

"‐" denotes not reported

aThe number of participants finishing the trial is taken from clinicaltrials.gov and is the number of individuals who completed the trial as defined by investigator.

bTwenty of the randomised participants are not included in the analysis. It is unknown to which group they belong. Therefore the total number of randomised participants does not equal the sum of the number of randomised patients in each intervention group.

cThe number of randomised participants to each comparator group is not reported. Only the 18 participants finishing the trial are described in the publication.

dIt is reported that 25 participants were randomised, but only the 22 participants who completed the trial are presented.

eData after 52 weeks of double‐blind intervention. From the double‐blind intervention period to the open‐label extension of 91 weeks 84 participants discontinued in the glimepiride group, 70 in the liraglutide 1.2 mg group and 71 in the liraglutide 1.8 mg group.

fIt is not described in the publication to which group the three patients who were lost to follow‐up belonged. However, it is stated in the publication that 100 participants were randomised.

gA total of 72 participants underwent randomisation, but only 55 participants are included in the analyses of the trial. Eleven participants were excluded because they had received sulphonylurea previously, but the authors did not report to which group they initially were randomised.

hIn the publication there is a discrepancy in the number of participants finishing the study.

iThe number of patients screened is the number screened to the initial 52 weeks (Charbonnel 2005).

jThe numbers for chlorpropamide and insulin interventions are the number of participants randomised to 'Glucose Study 1' plus the number of participants randomised to 'Glucose Study 2'. Lost to follow‐up mortality is not explicitly explained for each antidiabetic intervention group. For 'Glucose Study 1' vital status was unknown for 57 participants in the intensive intervention group (chlorpropamide/glibenclamide/insulin).

kThe number of total is not the same as the number of I and C together, as some of the trials only reported the total number of participants randomised (Fineberg 1980; Hermann 1991; Pagano 1995). Several trials did not report the number of participants finishing study.

ADOPT: A Diabetes Outcome Progression Trial; APPROACH: Assessment on the Prevention of Progression by Rosiglitazone on Atherosclerosis in Type 2 Diabetes Patients with Cardiovascular History; C: control; I: intervention; LEAD‐3: Liraglutide Effect and Action in Diabetes‐3; N/A: not acknowledged; T: total; UKPDS: United Kingdom Prospective Diabetes Study

Figuras y tablas -
Table 1. Overview of study populations
Ir a la tabla de la revisión
Comparison 1. Sulphonylureas versus placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

5

883

Risk Ratio (M‐H, Random, 95% CI)

1.51 [0.91, 2.52]

1.1 First‐generation SU

2

553

Risk Ratio (M‐H, Random, 95% CI)

1.46 [0.87, 2.45]

1.2 Second‐generation SU

3

330

Risk Ratio (M‐H, Random, 95% CI)

4.86 [0.24, 99.94]

1.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 All‐cause mortality; best‐worst case scenario Show forest plot

1

57

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 Second‐generation SU

1

57

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 All‐cause mortality; worst‐best case scenario Show forest plot

1

57

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.2 Second‐generation SU

1

57

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4 Cardiovascular mortality Show forest plot

5

883

Risk Ratio (M‐H, Random, 95% CI)

2.64 [1.35, 5.17]

4.1 First‐generation SU

2

553

Risk Ratio (M‐H, Random, 95% CI)

2.63 [1.32, 5.22]

4.2 Second‐generation SU

3

330

Risk Ratio (M‐H, Random, 95% CI)

2.91 [0.12, 70.71]

4.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Non‐fatal macrovascular outcomes Show forest plot

1

205

Risk Ratio (M‐H, Random, 95% CI)

1.32 [0.82, 2.13]

5.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5.2 Second‐generation SU

1

205

Risk Ratio (M‐H, Random, 95% CI)

1.32 [0.82, 2.13]

5.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Non‐fatal myocardial infarction Show forest plot

1

409

Risk Ratio (M‐H, Random, 95% CI)

0.80 [0.43, 1.51]

6.1 First‐generation SU

1

409

Risk Ratio (M‐H, Random, 95% CI)

0.80 [0.43, 1.51]

6.2 Second‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7 Amputation of lower extremity Show forest plot

1

409

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.01, 4.16]

7.1 First‐generation SU

1

409

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.01, 4.16]

7.2 Second‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 Nephropathy Show forest plot

1

409

Risk Ratio (M‐H, Random, 95% CI)

1.26 [0.34, 4.61]

8.1 First‐generation SU

1

409

Risk Ratio (M‐H, Random, 95% CI)

1.26 [0.34, 4.61]

8.2 Second‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9 Retinopathy Show forest plot

1

409

Risk Ratio (M‐H, Random, 95% CI)

0.93 [0.67, 1.30]

9.1 First‐generation SU

1

409

Risk Ratio (M‐H, Random, 95% CI)

0.93 [0.67, 1.30]

9.2 Second‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10 Change in fasting blood glucose from baseline (mmol/L) Show forest plot

6

342

Mean Difference (IV, Random, 95% CI)

‐1.35 [‐2.00, ‐0.69]

10.1 First‐generation SU

1

128

Mean Difference (IV, Random, 95% CI)

‐2.1 [‐3.19, ‐1.01]

10.2 Second‐generation SU

5

214

Mean Difference (IV, Random, 95% CI)

‐1.20 [‐1.94, ‐0.46]

10.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

11 Change in HbA1c from baseline (%) Show forest plot

6

342

Mean Difference (IV, Random, 95% CI)

1.00 [‐1.21, ‐0.79]

11.1 First‐generation SU

1

128

Mean Difference (IV, Random, 95% CI)

‐0.94 [‐1.29, ‐0.59]

11.2 Second‐generation SU

5

214

Mean Difference (IV, Random, 95% CI)

‐1.02 [‐1.32, ‐0.72]

11.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

12 Change in BMI from baseline (kg/m2) Show forest plot

3

141

Mean Difference (IV, Random, 95% CI)

‐0.09 [‐0.59, 0.41]

12.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

12.2 Second‐generation SU

3

141

Mean Difference (IV, Random, 95% CI)

‐0.09 [‐0.59, 0.41]

12.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

13 Change in weight from baseline (kg) Show forest plot

1

128

Mean Difference (IV, Random, 95% CI)

‐0.40 [‐1.36, 0.56]

13.1 First‐generation SU

1

128

Mean Difference (IV, Random, 95% CI)

‐0.40 [‐1.36, 0.56]

13.2 Second‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

13.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

14 Adverse events Show forest plot

3

346

Risk Ratio (M‐H, Random, 95% CI)

1.23 [0.92, 1.64]

14.1 First‐generation SU

1

144

Risk Ratio (M‐H, Random, 95% CI)

1.35 [0.97, 1.88]

14.2 Second‐generation SU

2

202

Risk Ratio (M‐H, Random, 95% CI)

0.91 [0.51, 1.62]

14.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

15 Drop‐outs due to adverse events Show forest plot

6

654

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.33, 1.36]

15.1 First‐generation SU

1

144

Risk Ratio (M‐H, Random, 95% CI)

0.75 [0.17, 3.23]

15.2 Second‐generation SU

5

510

Risk Ratio (M‐H, Random, 95% CI)

0.62 [0.24, 1.57]

15.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

16 Mild hypoglycaemia Show forest plot

1

134

Risk Ratio (M‐H, Random, 95% CI)

12.26 [0.70, 213.33]

16.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

16.2 Second‐generation SU

1

134

Risk Ratio (M‐H, Random, 95% CI)

12.26 [0.70, 213.33]

16.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

17 Severe hypoglycaemia Show forest plot

1

46

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

17.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

17.2 Second‐generation SU

1

46

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

17.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

18 Cancer Show forest plot

2

614

Risk Ratio (M‐H, Random, 95% CI)

0.54 [0.06, 5.05]

18.1 First‐generation SU

1

409

Risk Ratio (M‐H, Random, 95% CI)

0.25 [0.07, 0.88]

18.2 Second‐generation SU

1

205

Risk Ratio (M‐H, Random, 95% CI)

2.91 [0.12, 70.71]

18.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19 Intervention failure Show forest plot

4

794

Risk Ratio (M‐H, Random, 95% CI)

0.26 [0.07, 0.94]

19.1 First‐generation SU

1

409

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.44, 1.19]

19.2 Second‐generation SU

3

385

Risk Ratio (M‐H, Random, 95% CI)

0.13 [0.04, 0.44]

19.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Figuras y tablas -
Comparison 1. Sulphonylureas versus placebo
Ir a la tabla de la revisión
Comparison 2. Sulphonylureas versus metformin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

8

3768

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.61, 1.58]

1.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.2 Second‐generation SU

6

3528

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.61, 1.58]

1.3 Third‐generation SU

2

240

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 All‐cause mortality; best‐worst case scenario Show forest plot

5

283

Risk Ratio (M‐H, Random, 95% CI)

0.72 [0.12, 4.45]

2.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 Second‐generation SU

4

207

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.10, 10.25]

2.3 Third‐generation SU

1

76

Risk Ratio (M‐H, Random, 95% CI)

0.35 [0.01, 8.35]

3 All‐cause mortality; worst‐best case scenario Show forest plot

5

283

Risk Ratio (M‐H, Random, 95% CI)

1.81 [0.37, 8.71]

3.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.2 Second‐generation SU

4

207

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.10, 10.25]

3.3 Third‐generation SU

1

76

Risk Ratio (M‐H, Random, 95% CI)

3.16 [0.34, 29.06]

4 Cardiovascular mortality Show forest plot

8

3768

Risk Ratio (M‐H, Random, 95% CI)

1.47 [0.54, 4.01]

4.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4.2 Second‐generation SU

6

3528

Risk Ratio (M‐H, Random, 95% CI)

1.47 [0.54, 4.01]

4.3 Third‐generation SU

2

240

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Non‐fatal macrovascular outcomes Show forest plot

4

3094

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.48, 0.93]

5.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5.2 Second‐generation SU

3

3018

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.48, 0.93]

5.3 Third‐generation SU

1

76

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Non‐fatal myocardial infarction Show forest plot

4

3061

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.37, 2.85]

6.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6.2 Second‐generation SU

4

3061

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.37, 2.85]

6.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7 Non‐fatal stroke Show forest plot

1

44

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.2 Second‐generation SU

1

44

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 Amputation of lower extremity Show forest plot

1

44

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.2 Second‐generation SU

1

44

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9 Peripheral revascularisation Show forest plot

2

2946

Risk Ratio (M‐H, Random, 95% CI)

1.15 [0.69, 1.92]

9.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.2 Second‐generation SU

2

2946

Risk Ratio (M‐H, Random, 95% CI)

1.15 [0.69, 1.92]

9.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10 Microvascular outcomes Show forest plot

1

44

Risk Ratio (M‐H, Random, 95% CI)

2.0 [0.20, 20.49]

10.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.2 Second‐generation SU

1

44

Risk Ratio (M‐H, Random, 95% CI)

2.0 [0.20, 20.49]

10.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11 Nephropathy Show forest plot

1

44

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.07, 15.00]

11.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.2 Second‐generation SU

1

44

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.07, 15.00]

11.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12 Retinal photocoagulation Show forest plot

1

44

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.2 Second‐generation SU

1

44

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13 Change in fasting blood glucose from baseline (mmol/L) Show forest plot

15

4654

Mean Difference (IV, Random, 95% CI)

0.20 [‐0.07, 0.48]

13.1 First‐generation SU

2

482

Mean Difference (IV, Random, 95% CI)

0.13 [‐0.75, 1.01]

13.2 Second‐generation SU

11

3891

Mean Difference (IV, Random, 95% CI)

0.43 [0.10, 0.75]

13.3 Third‐generation SU

3

281

Mean Difference (IV, Random, 95% CI)

‐0.22 [‐0.52, 0.08]

14 Change in HbA1c from baseline (%) Show forest plot

13

3632

Mean Difference (IV, Random, 95% CI)

0.06 [‐0.16, 0.29]

14.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

14.2 Second‐generation SU

10

3351

Mean Difference (IV, Random, 95% CI)

0.17 [‐0.09, 0.44]

14.3 Third‐generation SU

3

281

Mean Difference (IV, Random, 95% CI)

‐0.18 [‐0.43, 0.07]

15 Change in BMI from baseline (kg/m2) Show forest plot

5

322

Mean Difference (IV, Random, 95% CI)

0.13 [‐0.69, 0.94]

15.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

15.2 Second‐generation SU

3

103

Mean Difference (IV, Random, 95% CI)

0.25 [‐1.21, 1.70]

15.3 Third‐generation SU

2

219

Mean Difference (IV, Random, 95% CI)

‐0.10 [‐1.06, 0.86]

16 Change in weight from baseline (kg) Show forest plot

7

3497

Mean Difference (IV, Random, 95% CI)

3.77 [3.06, 4.47]

16.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

16.2 Second‐generation SU

7

3497

Mean Difference (IV, Random, 95% CI)

3.77 [3.06, 4.47]

16.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

17 Adverse events Show forest plot

5

3118

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.97, 1.01]

17.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

17.2 Second‐generation SU

4

3042

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.97, 1.01]

17.3 Third‐generation SU

1

76

Risk Ratio (M‐H, Random, 95% CI)

3.16 [0.13, 75.16]

18 Serious adverse events Show forest plot

5

3175

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.82, 1.07]

18.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

18.2 Second‐generation SU

4

3011

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.82, 1.07]

18.3 Third‐generation SU

1

164

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19 Drop‐outs due to adverse events Show forest plot

8

3731

Risk Ratio (M‐H, Random, 95% CI)

1.18 [0.98, 1.41]

19.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19.2 Second‐generation SU

7

3567

Risk Ratio (M‐H, Random, 95% CI)

1.19 [0.99, 1.42]

19.3 Third‐generation SU

1

164

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.01, 4.20]

20 Mild hypoglycaemia Show forest plot

6

4827

Risk Ratio (M‐H, Fixed, 95% CI)

3.16 [2.74, 3.64]

20.1 First‐generation SU

1

607

Risk Ratio (M‐H, Fixed, 95% CI)

1.89 [1.00, 3.58]

20.2 Second‐generation SU

5

4056

Risk Ratio (M‐H, Fixed, 95% CI)

3.24 [2.80, 3.76]

20.3 Third‐generation SU

1

164

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

21 Moderate hypoglycaemia Show forest plot

1

44

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.13, 69.87]

21.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

21.2 Second‐generation SU

1

44

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.13, 69.87]

21.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

22 Severe hypoglycaemia Show forest plot

5

4408

Risk Ratio (M‐H, Random, 95% CI)

4.50 [1.24, 16.31]

22.1 First‐generation SU

1

607

Risk Ratio (M‐H, Random, 95% CI)

2.58 [0.24, 28.31]

22.2 Second‐generation SU

4

3637

Risk Ratio (M‐H, Random, 95% CI)

5.64 [1.22, 26.00]

22.3 Third‐generation SU

1

164

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23 Cancer Show forest plot

1

2902

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.76, 1.61]

23.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.2 Second‐generation SU

1

2902

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.76, 1.61]

23.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24 Intervention failure Show forest plot

9

4990

Risk Ratio (M‐H, Random, 95% CI)

0.92 [0.60, 1.39]

24.1 First‐generation SU

1

607

Risk Ratio (M‐H, Random, 95% CI)

0.63 [0.36, 1.09]

24.2 Second‐generation SU

7

4143

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.60, 1.57]

24.3 Third‐generation SU

2

240

Risk Ratio (M‐H, Random, 95% CI)

1.23 [0.43, 3.50]
Figuras y tablas -
Comparison 2. Sulphonylureas versus metformin
Ir a la tabla de la revisión
Comparison 3. Sulphonylureas versus thiazolidinediones

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

8

5030

Risk Ratio (M‐H, Random, 95% CI)

0.92 [0.60, 1.41]

1.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.2 Second‐generation SU

7

4955

Risk Ratio (M‐H, Random, 95% CI)

0.92 [0.60, 1.41]

1.3 Third‐generation SU

1

75

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 All‐cause mortality; best‐worst case scenario Show forest plot

5

1327

Risk Ratio (M‐H, Random, 95% CI)

0.18 [0.06, 0.54]

2.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 Second‐generation SU

4

1252

Risk Ratio (M‐H, Random, 95% CI)

0.18 [0.06, 0.54]

2.3 Third‐generation SU

1

75

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 All‐cause mortality; worst‐best case scenario Show forest plot

5

1327

Risk Ratio (M‐H, Random, 95% CI)

7.49 [1.39, 40.18]

3.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.2 Second‐generation SU

4

1252

Risk Ratio (M‐H, Random, 95% CI)

9.76 [0.59, 161.27]

3.3 Third‐generation SU

1

75

Risk Ratio (M‐H, Random, 95% CI)

7.18 [0.38, 134.45]

4 Cardiovascular mortality Show forest plot

8

5030

Risk Ratio (M‐H, Random, 95% CI)

1.30 [0.55, 3.07]

4.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4.2 Second‐generation SU

7

4955

Risk Ratio (M‐H, Random, 95% CI)

1.30 [0.55, 3.07]

4.3 Third‐generation SU

1

75

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Non‐fatal macrovascular outcomes Show forest plot

7

4675

Risk Ratio (M‐H, Random, 95% CI)

0.91 [0.62, 1.33]

5.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5.2 Second‐generation SU

6

4600

Risk Ratio (M‐H, Random, 95% CI)

0.91 [0.62, 1.33]

5.3 Third‐generation SU

1

75

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Non‐fatal myocardial infarction Show forest plot

7

4956

Risk Ratio (M‐H, Random, 95% CI)

0.68 [0.41, 1.14]

6.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6.2 Second‐generation SU

7

4956

Risk Ratio (M‐H, Random, 95% CI)

0.68 [0.41, 1.14]

6.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7 Non‐fatal stroke Show forest plot

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.02, 1.67]

7.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.2 Second‐generation SU

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.02, 1.67]

7.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 Amputation of lower extremity Show forest plot

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.2 Second‐generation SU

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9 Cardial revascularisation Show forest plot

2

707

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.61, 1.71]

9.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.2 Second‐generation SU

2

707

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.61, 1.71]

9.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10 Peripheral revascularisation Show forest plot

3

3612

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.54, 1.39]

10.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.2 Second‐generation SU

3

3612

Risk Ratio (M‐H, Random, 95% CI)

0.87 [0.54, 1.39]

10.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11 Microvascular outcomes Show forest plot

2

235

Risk Ratio (M‐H, Random, 95% CI)

0.83 [0.05, 13.16]

11.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.2 Second‐generation SU

2

235

Risk Ratio (M‐H, Random, 95% CI)

0.83 [0.05, 13.16]

11.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12 Nephropathy Show forest plot

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.11 [0.01, 2.02]

12.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.2 Second‐generation SU

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.11 [0.01, 2.02]

12.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13 Retinopathy Show forest plot

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.06, 15.64]

13.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13.2 Second‐generation SU

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.06, 15.64]

13.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14 Retinal photocoagulation Show forest plot

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.2 Second‐generation SU

2

707

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

15 Change in fasting blood glucose from baseline (mmol/L) Show forest plot

18

6731

Mean Difference (IV, Random, 95% CI)

0.53 [0.31, 0.75]

15.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

15.2 Second‐generation SU

14

6076

Mean Difference (IV, Random, 95% CI)

0.56 [0.33, 0.79]

15.3 Third‐generation SU

4

655

Mean Difference (IV, Random, 95% CI)

0.46 [‐0.22, 1.13]

16 Change in HbA1c from baseline (%) Show forest plot

21

7435

Mean Difference (IV, Random, 95% CI)

0.03 [‐0.10, 0.16]

16.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

16.2 Second‐generation SU

17

6776

Mean Difference (IV, Random, 95% CI)

0.06 [‐0.09, 0.20]

16.3 Third‐generation SU

4

659

Mean Difference (IV, Random, 95% CI)

‐0.09 [‐0.31, 0.14]

17 Change in BMI from baseline (kg/m2) Show forest plot

7

532

Mean Difference (IV, Random, 95% CI)

‐0.98 [‐1.18, ‐0.79]

17.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

17.2 Second‐generation SU

4

121

Mean Difference (IV, Random, 95% CI)

1.00 [‐1.20, ‐0.80]

17.3 Third‐generation SU

3

411

Mean Difference (IV, Random, 95% CI)

‐0.75 [‐1.58, 0.08]

18 Change in weight from baseline (kg) Show forest plot

11

5948

Mean Difference (IV, Random, 95% CI)

‐1.86 [‐2.50, ‐1.21]

18.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

18.2 Second‐generation SU

10

5779

Mean Difference (IV, Random, 95% CI)

‐1.90 [‐2.56, ‐1.25]

18.3 Third‐generation SU

1

169

Mean Difference (IV, Random, 95% CI)

0.20 [‐3.75, 4.15]

19 Adverse events Show forest plot

13

7001

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.94, 1.01]

19.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19.2 Second‐generation SU

10

6491

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.97, 1.01]

19.3 Third‐generation SU

3

510

Risk Ratio (M‐H, Random, 95% CI)

0.88 [0.78, 0.99]

20 Serious adverse events Show forest plot

11

5605

Risk Ratio (M‐H, Random, 95% CI)

0.90 [0.80, 1.01]

20.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

20.2 Second‐generation SU

8

4979

Risk Ratio (M‐H, Random, 95% CI)

0.90 [0.80, 1.01]

20.3 Third‐generation SU

3

626

Risk Ratio (M‐H, Random, 95% CI)

0.61 [0.21, 1.83]

21 Drop‐outs due to adverse events Show forest plot

17

7856

Risk Ratio (M‐H, Random, 95% CI)

1.16 [1.00, 1.34]

21.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

21.2 Second‐generation SU

15

7433

Risk Ratio (M‐H, Random, 95% CI)

1.15 [0.98, 1.36]

21.3 Third‐generation SU

2

423

Risk Ratio (M‐H, Random, 95% CI)

0.54 [0.15, 1.97]

22 Mild hypoglycaemia Show forest plot

9

6556

Risk Ratio (M‐H, Random, 95% CI)

3.95 [3.08, 5.06]

22.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

22.2 Second‐generation SU

8

6365

Risk Ratio (M‐H, Random, 95% CI)

4.05 [3.28, 5.00]

22.3 Third‐generation SU

1

191

Risk Ratio (M‐H, Random, 95% CI)

1.41 [0.47, 4.30]

23 Moderate hypoglycaemia Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24 Severe hypoglycaemia Show forest plot

8

6030

Risk Ratio (M‐H, Random, 95% CI)

6.11 [1.57, 23.79]

24.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24.2 Second‐generation SU

6

5660

Risk Ratio (M‐H, Random, 95% CI)

6.11 [1.57, 23.79]

24.3 Third‐generation SU

2

370

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

25 Cancer Show forest plot

6

4912

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.72, 1.45]

25.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

25.2 Second‐generation SU

6

4912

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.72, 1.45]

25.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

26 Intervention failure Show forest plot

10

6757

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.65, 1.45]

26.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

26.2 Second‐generation SU

8

6438

Risk Ratio (M‐H, Random, 95% CI)

1.10 [0.73, 1.65]

26.3 Third‐generation SU

2

319

Risk Ratio (M‐H, Random, 95% CI)

0.24 [0.08, 0.75]
Figuras y tablas -
Comparison 3. Sulphonylureas versus thiazolidinediones
Ir a la tabla de la revisión
Comparison 4. Sulphonylureas versus insulin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

5

3586

Risk Ratio (M‐H, Random, 95% CI)

1.05 [0.92, 1.21]

1.1 First‐generation SU

2

1944

Risk Ratio (M‐H, Random, 95% CI)

1.18 [0.88, 1.59]

1.2 Second‐generation SU

4

1642

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.79, 1.18]

1.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 All‐cause mortality; best‐worst case scenario Show forest plot

2

80

Risk Ratio (M‐H, Random, 95% CI)

0.13 [0.02, 0.95]

2.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 Second‐generation SU

2

80

Risk Ratio (M‐H, Random, 95% CI)

0.13 [0.02, 0.95]

2.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 All‐cause mortality; worst‐best case scenario Show forest plot

2

80

Risk Ratio (M‐H, Random, 95% CI)

3.54 [0.83, 15.00]

3.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.2 Second‐generation SU

2

80

Risk Ratio (M‐H, Random, 95% CI)

3.54 [0.83, 15.00]

3.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4 Cardiovascular mortality Show forest plot

5

3586

Risk Ratio (M‐H, Random, 95% CI)

1.09 [0.82, 1.44]

4.1 First‐generation SU

2

1944

Risk Ratio (M‐H, Random, 95% CI)

1.36 [0.68, 2.71]

4.2 Second‐generation SU

4

1642

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.73, 1.28]

4.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Non‐fatal myocardial infarction Show forest plot

2

3470

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.79, 1.23]

5.1 First‐generation SU

2

1944

Risk Ratio (M‐H, Random, 95% CI)

1.08 [0.81, 1.45]

5.2 Second‐generation SU

1

1526

Risk Ratio (M‐H, Random, 95% CI)

0.86 [0.61, 1.22]

5.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Non‐fatal stroke Show forest plot

2

3470

Risk Ratio (M‐H, Random, 95% CI)

1.45 [1.02, 2.06]

6.1 First‐generation SU

2

1944

Risk Ratio (M‐H, Random, 95% CI)

1.23 [0.74, 2.05]

6.2 Second‐generation SU

1

1526

Risk Ratio (M‐H, Random, 95% CI)

1.68 [1.04, 2.71]

6.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7 Amputation of lower extremity Show forest plot

2

3470

Risk Ratio (M‐H, Random, 95% CI)

0.49 [0.24, 1.00]

7.1 First‐generation SU

2

1944

Risk Ratio (M‐H, Random, 95% CI)

0.49 [0.18, 1.34]

7.2 Second‐generation SU

1

1526

Risk Ratio (M‐H, Random, 95% CI)

0.49 [0.18, 1.35]

7.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 Microvascular outcomes Show forest plot

1

3056

Risk Ratio (M‐H, Random, 95% CI)

1.12 [0.82, 1.53]

8.1 First‐generation SU

1

1530

Risk Ratio (M‐H, Random, 95% CI)

1.30 [0.95, 1.77]

8.2 Second‐generation SU

1

1526

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.67, 1.33]

8.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9 Nephropathy Show forest plot

1

414

Risk Ratio (M‐H, Random, 95% CI)

11.32 [0.63, 203.45]

9.1 First‐generation SU

1

414

Risk Ratio (M‐H, Random, 95% CI)

11.32 [0.63, 203.45]

9.2 Second‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10 Retinopathy Show forest plot

1

414

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.71, 1.39]

10.1 First‐generation SU

1

414

Risk Ratio (M‐H, Random, 95% CI)

0.99 [0.71, 1.39]

10.2 Second‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11 Retinal photocoagulation Show forest plot

1

3056

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.80, 1.31]

11.1 First‐generation SU

1

1530

Risk Ratio (M‐H, Random, 95% CI)

1.12 [0.80, 1.57]

11.2 Second‐generation SU

1

1526

Risk Ratio (M‐H, Random, 95% CI)

0.93 [0.65, 1.32]

11.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12 Change in fasting blood glucose from baseline (mmol/L) Show forest plot

5

2423

Mean Difference (IV, Random, 95% CI)

0.12 [‐0.37, 0.61]

12.1 First‐generation SU

1

1122

Mean Difference (IV, Random, 95% CI)

‐0.40 [‐0.69, ‐0.11]

12.2 Second‐generation SU

5

1301

Mean Difference (IV, Random, 95% CI)

0.29 [‐0.02, 0.61]

12.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

13 Change in HbA1c from baseline (%) Show forest plot

6

2566

Mean Difference (IV, Random, 95% CI)

‐0.09 [‐0.20, 0.03]

13.1 First‐generation SU

1

1122

Mean Difference (IV, Random, 95% CI)

‐0.20 [‐0.38, ‐0.02]

13.2 Second‐generation SU

6

1444

Mean Difference (IV, Random, 95% CI)

‐0.03 [‐0.17, 0.10]

13.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

14 Change in BMI from baseline (kg/m2) Show forest plot

1

34

Mean Difference (IV, Random, 95% CI)

‐1.70 [‐4.10, 0.70]

14.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

14.2 Second‐generation SU

1

34

Mean Difference (IV, Random, 95% CI)

‐1.70 [‐4.10, 0.70]

14.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

15 Change in weight from baseline (kg) Show forest plot

5

2514

Mean Difference (IV, Random, 95% CI)

1.00 [‐2.82, 0.83]

15.1 First‐generation SU

1

1122

Mean Difference (IV, Random, 95% CI)

‐2.30 [‐4.11, ‐0.49]

15.2 Second‐generation SU

5

1392

Mean Difference (IV, Random, 95% CI)

‐0.37 [‐2.39, 1.65]

15.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

16 Adverse events Show forest plot

1

143

Risk Ratio (M‐H, Random, 95% CI)

1.06 [0.68, 1.65]

16.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

16.2 Second‐generation SU

1

143

Risk Ratio (M‐H, Random, 95% CI)

1.06 [0.68, 1.65]

16.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

17 Drop‐outs due to adverse events Show forest plot

2

192

Risk Ratio (M‐H, Random, 95% CI)

3.54 [0.43, 29.43]

17.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

17.2 Second‐generation SU

2

192

Risk Ratio (M‐H, Random, 95% CI)

3.54 [0.43, 29.43]

17.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

18 Mild hypoglycaemia Show forest plot

2

3105

Risk Ratio (M‐H, Random, 95% CI)

0.94 [0.45, 1.95]

18.1 First‐generation SU

1

1530

Risk Ratio (M‐H, Random, 95% CI)

0.57 [0.42, 0.78]

18.2 Second‐generation SU

2

1575

Risk Ratio (M‐H, Random, 95% CI)

1.41 [1.13, 1.76]

18.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19 Severe hypoglycaemia Show forest plot

4

3172

Risk Ratio (M‐H, Random, 95% CI)

1.27 [0.38, 4.24]

19.1 First‐generation SU

1

1530

Risk Ratio (M‐H, Random, 95% CI)

0.59 [0.11, 3.02]

19.2 Second‐generation SU

4

1642

Risk Ratio (M‐H, Random, 95% CI)

2.07 [0.66, 6.50]

19.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

20 Cancer Show forest plot

3

3519

Risk Ratio (M‐H, Random, 95% CI)

1.01 [0.75, 1.36]

20.1 First‐generation SU

2

1944

Risk Ratio (M‐H, Random, 95% CI)

0.81 [0.29, 2.27]

20.2 Second‐generation SU

2

1575

Risk Ratio (M‐H, Random, 95% CI)

0.95 [0.61, 1.49]

20.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

21 Intervention failure Show forest plot

4

3200

Risk Ratio (M‐H, Random, 95% CI)

1.24 [0.67, 2.27]

21.1 First‐generation SU

1

1530

Risk Ratio (M‐H, Random, 95% CI)

0.62 [0.44, 0.89]

21.2 Second‐generation SU

4

1670

Risk Ratio (M‐H, Random, 95% CI)

1.96 [0.80, 4.76]

21.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Figuras y tablas -
Comparison 4. Sulphonylureas versus insulin
Ir a la tabla de la revisión
Comparison 5. Sulphonylureas versus alpha‐glucosidase inhibitors

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

6

714

Risk Ratio (M‐H, Random, 95% CI)

2.25 [0.43, 11.84]

1.1 First‐generation SU

2

246

Risk Ratio (M‐H, Random, 95% CI)

3.16 [0.13, 76.44]

1.2 Second‐generation SU

4

468

Risk Ratio (M‐H, Random, 95% CI)

1.98 [0.28, 13.86]

1.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 All‐cause mortality; best‐worst case scenario Show forest plot

2

90

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 Second‐generation SU

2

90

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 All‐cause mortality; worst‐best case scenario Show forest plot

2

90

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.2 Second‐generation SU

2

90

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4 Cardiovascular mortality Show forest plot

6

708

Risk Ratio (M‐H, Random, 95% CI)

2.39 [0.30, 19.28]

4.1 First‐generation SU

2

242

Risk Ratio (M‐H, Random, 95% CI)

3.0 [0.12, 72.44]

4.2 Second‐generation SU

4

466

Risk Ratio (M‐H, Random, 95% CI)

2.02 [0.13, 31.96]

4.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Non‐fatal macrovascular outcomes Show forest plot

2

345

Risk Ratio (M‐H, Random, 95% CI)

1.61 [1.06, 2.44]

5.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5.2 Second‐generation SU

2

345

Risk Ratio (M‐H, Random, 95% CI)

1.61 [1.06, 2.44]

5.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Non‐fatal myocardial infarction Show forest plot

2

133

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.06, 14.92]

6.1 First‐generation SU

1

98

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.06, 14.92]

6.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7 Non‐fatal stroke Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 Amputation of lower extremity Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9 Cardial revascularisation Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10 Peripheral revascularisation Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11 Microvascular outcomes Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12 Nephropathy Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13 Retinopathy Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14 Retinal photocoagulation Show forest plot

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.2 Second‐generation SU

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

15 Change in fasting blood glucose from baseline (mmol/L) Show forest plot

11

915

Mean Difference (IV, Random, 95% CI)

‐0.46 [‐0.80, ‐0.11]

15.1 First‐generation SU

2

208

Mean Difference (IV, Random, 95% CI)

‐1.16 [‐1.92, ‐0.41]

15.2 Second‐generation SU

8

488

Mean Difference (IV, Random, 95% CI)

‐0.16 [‐0.42, 0.11]

15.3 Third‐generation SU

1

219

Mean Difference (IV, Random, 95% CI)

‐1.20 [‐1.92, ‐0.48]

16 Change in HbA1c from baseline (%) Show forest plot

13

968

Mean Difference (IV, Random, 95% CI)

‐0.20 [‐0.46, 0.06]

16.1 First‐generation SU

2

208

Mean Difference (IV, Random, 95% CI)

‐0.50 [‐0.79, ‐0.20]

16.2 Second‐generation SU

10

541

Mean Difference (IV, Random, 95% CI)

‐0.06 [‐0.36, 0.24]

16.3 Third‐generation SU

1

219

Mean Difference (IV, Random, 95% CI)

‐0.7 [‐1.28, ‐0.12]

17 Change in BMI from baseline (kg/m2) Show forest plot

5

232

Mean Difference (IV, Random, 95% CI)

‐0.02 [‐0.20, 0.16]

17.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

17.2 Second‐generation SU

5

232

Mean Difference (IV, Random, 95% CI)

‐0.02 [‐0.20, 0.16]

17.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

18 Change in weight from baseline (kg) Show forest plot

7

689

Mean Difference (IV, Random, 95% CI)

0.81 [‐0.61, 2.23]

18.1 First‐generation SU

1

132

Mean Difference (IV, Random, 95% CI)

3.2 [2.29, 4.11]

18.2 Second‐generation SU

5

338

Mean Difference (IV, Random, 95% CI)

‐0.22 [‐0.47, 0.03]

18.3 Third‐generation SU

1

219

Mean Difference (IV, Random, 95% CI)

1.5 [0.28, 2.72]

19 Adverse events Show forest plot

11

1111

Risk Ratio (M‐H, Random, 95% CI)

0.65 [0.51, 0.82]

19.1 First‐generation SU

2

246

Risk Ratio (M‐H, Random, 95% CI)

0.63 [0.52, 0.76]

19.2 Second‐generation SU

8

646

Risk Ratio (M‐H, Random, 95% CI)

0.64 [0.39, 1.03]

19.3 Third‐generation SU

1

219

Risk Ratio (M‐H, Random, 95% CI)

0.64 [0.53, 0.78]

20 Serious adverse events Show forest plot

3

229

Risk Ratio (M‐H, Random, 95% CI)

0.52 [0.09, 3.03]

20.1 First‐generation SU

1

98

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.14, 6.55]

20.2 Second‐generation SU

2

131

Risk Ratio (M‐H, Random, 95% CI)

0.15 [0.01, 2.81]

20.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

21 Drop‐outs due to adverse events Show forest plot

12

1335

Risk Ratio (M‐H, Random, 95% CI)

0.37 [0.22, 0.63]

21.1 First‐generation SU

2

246

Risk Ratio (M‐H, Random, 95% CI)

0.28 [0.12, 0.67]

21.2 Second‐generation SU

9

870

Risk Ratio (M‐H, Random, 95% CI)

0.48 [0.24, 0.96]

21.3 Third‐generation SU

1

219

Risk Ratio (M‐H, Random, 95% CI)

0.19 [0.02, 1.64]

22 Mild hypoglycaemia Show forest plot

6

636

Risk Ratio (M‐H, Random, 95% CI)

8.59 [2.62, 28.12]

22.1 First‐generation SU

1

98

Risk Ratio (M‐H, Random, 95% CI)

2.88 [0.12, 69.07]

22.2 Second‐generation SU

4

319

Risk Ratio (M‐H, Random, 95% CI)

12.63 [0.73, 219.86]

22.3 Third‐generation SU

1

219

Risk Ratio (M‐H, Random, 95% CI)

9.73 [2.33, 40.63]

23 Moderate hypoglycaemia Show forest plot

3

183

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.2 Second‐generation SU

3

183

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24 Severe hypoglycaemia Show forest plot

5

500

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24.1 First‐generation SU

1

98

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24.2 Second‐generation SU

3

183

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24.3 Third‐generation SU

1

219

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

25 Cancer Show forest plot

3

443

Risk Ratio (M‐H, Random, 95% CI)

0.90 [0.11, 7.27]

25.1 First‐generation SU

1

98

Risk Ratio (M‐H, Random, 95% CI)

0.32 [0.01, 7.67]

25.2 Second‐generation SU

2

345

Risk Ratio (M‐H, Random, 95% CI)

1.98 [0.13, 31.35]

25.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

26 Intervention failure Show forest plot

5

831

Risk Ratio (M‐H, Random, 95% CI)

0.32 [0.18, 0.57]

26.1 First‐generation SU

1

98

Risk Ratio (M‐H, Random, 95% CI)

0.32 [0.01, 7.67]

26.2 Second‐generation SU

3

514

Risk Ratio (M‐H, Random, 95% CI)

0.25 [0.07, 0.92]

26.3 Third‐generation SU

1

219

Risk Ratio (M‐H, Random, 95% CI)

0.34 [0.17, 0.65]
Figuras y tablas -
Comparison 5. Sulphonylureas versus alpha‐glucosidase inhibitors
Ir a la tabla de la revisión
Comparison 6. Sulphonylureas versus incretin‐based intervention

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

3

2249

Risk Ratio (M‐H, Random, 95% CI)

1.57 [0.62, 4.00]

1.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.2 Second‐generation SU

2

1503

Risk Ratio (M‐H, Random, 95% CI)

1.39 [0.52, 3.68]

1.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

6.01 [0.25, 147.05]

2 All‐cause mortality; best‐worst case scenario Show forest plot

1

1092

Risk Ratio (M‐H, Random, 95% CI)

0.39 [0.18, 0.84]

2.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 Second‐generation SU

1

1092

Risk Ratio (M‐H, Random, 95% CI)

0.39 [0.18, 0.84]

2.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 All‐cause mortality; worst‐best case scenario Show forest plot

1

1092

Risk Ratio (M‐H, Random, 95% CI)

3.67 [1.50, 8.97]

3.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.2 Second‐generation SU

1

1092

Risk Ratio (M‐H, Random, 95% CI)

3.67 [1.50, 8.97]

3.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4 Cardiovascular mortality Show forest plot

2

1157

Risk Ratio (M‐H, Random, 95% CI)

6.01 [0.25, 147.05]

4.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

6.01 [0.25, 147.05]

5 Non‐fatal macrovascular outcomes Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

1.61 [0.82, 3.17]

5.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

1.61 [0.82, 3.17]

5.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Non‐fatal myocardial infarction Show forest plot

2

1157

Risk Ratio (M‐H, Random, 95% CI)

0.66 [0.10, 4.19]

6.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.65 [0.03, 15.85]

6.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.07, 6.40]

7 Non‐fatal stroke Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

3.91 [0.36, 42.79]

7.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

3.91 [0.36, 42.79]

7.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 Amputation of lower extremity Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9 Cardial revascularisation Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10 Peripheral revascularisation Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11 Microvascular outcomes Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

1.09 [0.52, 2.29]

11.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

1.09 [0.52, 2.29]

11.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12 Nephropathy Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.09, 10.70]

12.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.09, 10.70]

12.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13 Retinopathy Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

1.10 [0.50, 2.43]

13.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

1.10 [0.50, 2.43]

13.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14 Retinal photocoagulation Show forest plot

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

15 Change in fasting blood glucose from baseline (mmol/L) Show forest plot

3

1948

Mean Difference (IV, Random, 95% CI)

0.34 [‐0.44, 1.13]

15.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

15.2 Second‐generation SU

2

1202

Mean Difference (IV, Random, 95% CI)

0.11 [‐1.07, 1.28]

15.3 Third‐generation SU

1

746

Mean Difference (IV, Random, 95% CI)

0.8 [0.34, 1.26]

16 Change in HbA1c from baseline (%) Show forest plot

3

1950

Mean Difference (IV, Random, 95% CI)

0.35 [0.05, 0.64]

16.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

16.2 Second‐generation SU

2

1204

Mean Difference (IV, Random, 95% CI)

0.26 [‐0.23, 0.75]

16.3 Third‐generation SU

1

746

Mean Difference (IV, Random, 95% CI)

0.5 [0.32, 0.68]

17 Change in BMI from baseline (kg/m2) Show forest plot

1

400

Mean Difference (IV, Random, 95% CI)

0.7 [0.52, 0.88]

17.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

17.2 Second‐generation SU

1

400

Mean Difference (IV, Random, 95% CI)

0.7 [0.52, 0.88]

17.3 Third‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

18 Change in weight from baseline (kg) Show forest plot

3

1952

Mean Difference (IV, Random, 95% CI)

1.96 [0.63, 3.28]

18.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

18.2 Second‐generation SU

2

1206

Mean Difference (IV, Random, 95% CI)

1.31 [0.33, 2.29]

18.3 Third‐generation SU

1

746

Mean Difference (IV, Random, 95% CI)

3.30 [2.64, 3.96]

19 Adverse events Show forest plot

2

1157

Risk Ratio (M‐H, Random, 95% CI)

0.89 [0.74, 1.08]

19.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.90, 1.04]

19.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.73, 0.92]

20 Serious adverse events Show forest plot

2

1157

Risk Ratio (M‐H, Random, 95% CI)

1.22 [0.77, 1.94]

20.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

20.2 Second‐generation SU

1

411

Risk Ratio (M‐H, Random, 95% CI)

1.37 [0.71, 2.63]

20.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

1.09 [0.56, 2.10]

21 Drop‐outs due to adverse events Show forest plot

3

2249

Risk Ratio (M‐H, Random, 95% CI)

0.89 [0.64, 1.24]

21.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

21.2 Second‐generation SU

2

1503

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.67, 1.50]

21.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

0.70 [0.40, 1.24]

22 Mild hypoglycaemia Show forest plot

3

2249

Risk Ratio (M‐H, Random, 95% CI)

2.07 [1.44, 2.97]

22.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

22.2 Second‐generation SU

2

1503

Risk Ratio (M‐H, Random, 95% CI)

1.99 [1.02, 3.87]

22.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

2.41 [1.71, 3.40]

23 Severe hypoglycaemia Show forest plot

3

2249

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.2 Second‐generation SU

2

1503

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24 Intervention failure Show forest plot

3

2249

Risk Ratio (M‐H, Random, 95% CI)

1.31 [0.56, 3.05]

24.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24.2 Second‐generation SU

2

1503

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.41, 2.43]

24.3 Third‐generation SU

1

746

Risk Ratio (M‐H, Random, 95% CI)

2.09 [1.22, 3.59]
Figuras y tablas -
Comparison 6. Sulphonylureas versus incretin‐based intervention
Ir a la tabla de la revisión
Comparison 7. Sulphonylureas versus meglitinide

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

7

2038

Risk Ratio (M‐H, Random, 95% CI)

1.44 [0.47, 4.42]

1.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.2 Second‐generation SU

7

2038

Risk Ratio (M‐H, Random, 95% CI)

1.44 [0.47, 4.42]

1.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 All‐cause mortality; best‐worst case scenario Show forest plot

2

209

Risk Ratio (M‐H, Random, 95% CI)

0.07 [0.00, 1.16]

2.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 Second‐generation SU

2

209

Risk Ratio (M‐H, Random, 95% CI)

0.07 [0.00, 1.16]

2.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 All‐cause mortality; worst‐best case scenario Show forest plot

2

209

Risk Ratio (M‐H, Random, 95% CI)

15.17 [0.88, 261.61]

3.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3.2 Second‐generation SU

2

209

Risk Ratio (M‐H, Random, 95% CI)

15.17 [0.88, 261.61]

3.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4 Cardiovascular mortality Show forest plot

7

2038

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.27, 3.53]

4.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4.2 Second‐generation SU

7

2038

Risk Ratio (M‐H, Random, 95% CI)

0.97 [0.27, 3.53]

4.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Non‐fatal macrovascular outcomes Show forest plot

3

866

Risk Ratio (M‐H, Random, 95% CI)

0.50 [0.20, 1.20]

5.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5.2 Second‐generation SU

3

866

Risk Ratio (M‐H, Random, 95% CI)

0.50 [0.20, 1.20]

5.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Non‐fatal myocardial infarction Show forest plot

3

726

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.26, 4.08]

6.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6.2 Second‐generation SU

3

726

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.26, 4.08]

6.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7 Non‐fatal stroke Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 Amputation of lower extremity Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9 Cardial revascularisation Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10 Peripheral revascularisation Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11 Microvascular outcomes Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12 Nephropathy Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

12.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13 Retinopathy Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

13.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14 Retinal photocoagulation Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

14.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

15 Change in fasting blood glucose from baseline (mmol/L) Show forest plot

10

2329

Mean Difference (IV, Random, 95% CI)

‐0.21 [‐0.45, 0.03]

15.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

15.2 Second‐generation SU

9

2205

Mean Difference (IV, Random, 95% CI)

‐0.27 [‐0.51, ‐0.02]

15.3 Third‐generation SU

1

124

Mean Difference (IV, Random, 95% CI)

0.20 [‐0.22, 0.62]

16 Change in HbA1c from baseline (%) Show forest plot

10

2345

Mean Difference (IV, Random, 95% CI)

0.05 [‐0.09, 0.19]

16.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

16.2 Second‐generation SU

9

2221

Mean Difference (IV, Random, 95% CI)

0.07 [‐0.08, 0.22]

16.3 Third‐generation SU

1

124

Mean Difference (IV, Random, 95% CI)

‐0.10 [‐0.40, 0.20]

17 Change in BMI from baseline (kg/m2) Show forest plot

3

333

Mean Difference (IV, Random, 95% CI)

‐0.05 [‐0.25, 0.14]

17.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

17.2 Second‐generation SU

2

209

Mean Difference (IV, Random, 95% CI)

0.00 [‐0.19, 0.20]

17.3 Third‐generation SU

1

124

Mean Difference (IV, Random, 95% CI)

‐0.30 [‐0.66, 0.06]

18 Change in weight from baseline (kg) Show forest plot

5

1176

Mean Difference (IV, Random, 95% CI)

0.05 [‐0.40, 0.51]

18.1 First‐generation SU

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

18.2 Second‐generation SU

4

1052

Mean Difference (IV, Random, 95% CI)

0.13 [‐0.50, 0.76]

18.3 Third‐generation SU

1

124

Mean Difference (IV, Random, 95% CI)

0.10 [‐1.77, 1.97]

19 Adverse events Show forest plot

5

1829

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.95, 1.06]

19.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19.2 Second‐generation SU

5

1829

Risk Ratio (M‐H, Random, 95% CI)

1.00 [0.95, 1.06]

19.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

20 Drop‐outs due to adverse events Show forest plot

8

2151

Risk Ratio (M‐H, Random, 95% CI)

1.03 [0.79, 1.33]

20.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

20.2 Second‐generation SU

7

2019

Risk Ratio (M‐H, Random, 95% CI)

1.01 [0.78, 1.32]

20.3 Third‐generation SU

1

132

Risk Ratio (M‐H, Random, 95% CI)

5.0 [0.24, 102.19]

21 Serious adverse events Show forest plot

5

1829

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.74, 1.39]

21.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

21.2 Second‐generation SU

5

1829

Risk Ratio (M‐H, Random, 95% CI)

1.02 [0.74, 1.39]

21.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

22 Mild hypoglycaemia Show forest plot

6

1863

Risk Ratio (M‐H, Random, 95% CI)

1.20 [0.96, 1.49]

22.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

22.2 Second‐generation SU

6

1863

Risk Ratio (M‐H, Random, 95% CI)

1.20 [0.96, 1.49]

22.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23 Moderate hypoglycaemia Show forest plot

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.2 Second‐generation SU

1

34

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

23.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

24 Severe hypoglycaemia Show forest plot

6

1863

Risk Ratio (M‐H, Fixed, 95% CI)

2.87 [0.91, 8.99]

24.1 First‐generation SU

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

24.2 Second‐generation SU

6

1863

Risk Ratio (M‐H, Fixed, 95% CI)

2.87 [0.91, 8.99]

24.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

25 Cancer Show forest plot

2

290

Risk Ratio (M‐H, Random, 95% CI)

6.44 [0.27, 156.37]

25.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

25.2 Second‐generation SU

2

290

Risk Ratio (M‐H, Random, 95% CI)

6.44 [0.27, 156.37]

25.3 Third‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

26 Intervention failure Show forest plot

5

1656

Risk Ratio (M‐H, Random, 95% CI)

0.96 [0.69, 1.35]

26.1 First‐generation SU

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

26.2 Second‐generation SU

4

1524

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.69, 1.38]

26.3 Third‐generation SU

1

132

Risk Ratio (M‐H, Random, 95% CI)

0.67 [0.12, 3.86]
Figuras y tablas -
Comparison 7. Sulphonylureas versus meglitinide
Ir a la tabla de la revisión
Comparison 8. Second‐generation sulphonylureas versus first‐generation sulphonylureas

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

0.90 [0.72, 1.11]

2 Cardiovascular mortality Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.72, 1.34]

3 Non‐fatal myocardial infarction Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

0.80 [0.55, 1.16]

4 Non‐fatal stroke Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

1.32 [0.80, 2.17]

5 Amputation of lower extremity Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

1.01 [0.29, 3.46]

6 Microvascular outcomes Show forest plot

1

1234

Odds Ratio (M‐H, Random, 95% CI)

0.70 [0.48, 1.03]

7 Retinal photocoagulation Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.56, 1.20]

8 Change in fasting blood glucose from baseline (mmol/L) Show forest plot

2

936

Mean Difference (IV, Random, 95% CI)

0.62 [0.31, 0.94]

9 Change in HbA1c from baseline (%) Show forest plot

2

1014

Mean Difference (IV, Random, 95% CI)

‐1.44 [‐4.48, 1.60]

10 Change in weight from baseline (kg) Show forest plot

2

1014

Mean Difference (IV, Random, 95% CI)

1.80 [‐0.63, 4.23]

11 Mild hypoglycaemia Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

2.51 [1.83, 3.42]

12 Severe hypoglycaemia Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

3.52 [0.73, 16.89]

13 Cancer Show forest plot

1

1234

Risk Ratio (M‐H, Random, 95% CI)

0.81 [0.50, 1.31]

14 Intervention failure Show forest plot

3

1364

Risk Ratio (M‐H, Random, 95% CI)

1.96 [0.67, 5.75]
Figuras y tablas -
Comparison 8. Second‐generation sulphonylureas versus first‐generation sulphonylureas
Ir a la tabla de la revisión