Long‐term pharmacotherapy for obesity and overweight

Raj S Padwal; Diana Rucker; Stephanie K Li; Cintia Curioni; David CW Lau

doi:10.1002/14651858.CD004094.pub2

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Figure 1

QUOROM statement.

This QUOROM (quality of reporting of meta‐analyses) diagram reflects the updated search only (December 2002 to December 2006)

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Figure 2

Orlistat funnel plot.

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Analysis 1.1

Comparison 1 Orlistat: Anthropometric Outcomes, Outcome 1 Orlistat: Change in Weight (%).

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Analysis 1.2

Comparison 1 Orlistat: Anthropometric Outcomes, Outcome 2 Orlistat: Change in Weight (kg).

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Analysis 1.3

Comparison 1 Orlistat: Anthropometric Outcomes, Outcome 3 Orlistat: 5% Responders (absolute % difference).

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Analysis 1.4

Comparison 1 Orlistat: Anthropometric Outcomes, Outcome 4 Orlistat: 10% Responders (absolute % difference).

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Analysis 1.5

Comparison 1 Orlistat: Anthropometric Outcomes, Outcome 5 Orlistat: Change in Waist Circumference (cm).

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Analysis 1.6

Comparison 1 Orlistat: Anthropometric Outcomes, Outcome 6 Orlistat: Change in Body Mass Index (kg/m2).

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Analysis 1.7

Comparison 1 Orlistat: Anthropometric Outcomes, Outcome 7 Orlistat: Sensitivity Analysis According to Baseline CV Risk (Absolute Weight Loss).

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Analysis 1.8

Comparison 1 Orlistat: Anthropometric Outcomes, Outcome 8 Orlistat: Sensitivity Analysis According to Baseline CV Risk (% Weight Loss).

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Analysis 2.1

Comparison 2 Orlistat: Change in Blood Pressure, Outcome 1 Orlistat: Change in Systolic Blood Pressure (mm Hg).

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Analysis 2.2

Comparison 2 Orlistat: Change in Blood Pressure, Outcome 2 Orlistat: Change in Diastolic Blood Pressure (mm Hg).

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Analysis 3.1

Comparison 3 Orlistat: Change in Lipid Parameters, Outcome 1 Orlistat: Change in Total Cholesterol Levels.

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Analysis 3.2

Comparison 3 Orlistat: Change in Lipid Parameters, Outcome 2 Orlistat: Change in LDL cholesterol levels.

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Analysis 3.3

Comparison 3 Orlistat: Change in Lipid Parameters, Outcome 3 Orlistat: Change in HDL cholesterol Levels.

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Analysis 3.4

Comparison 3 Orlistat: Change in Lipid Parameters, Outcome 4 Orlistat: Change in Triglyceride Levels.

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Analysis 4.1

Comparison 4 Orlistat: Subgroup Analysis in Diabetes, Outcome 1 Change in Weight (%).

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Analysis 4.2

Comparison 4 Orlistat: Subgroup Analysis in Diabetes, Outcome 2 Change in Weight (kg).

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Analysis 4.3

Comparison 4 Orlistat: Subgroup Analysis in Diabetes, Outcome 3 Change in Fasting Glucose Levels (mmol/L).

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Analysis 4.4

Comparison 4 Orlistat: Subgroup Analysis in Diabetes, Outcome 4 Orlistat: Change in HgbA1c (%).

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Analysis 5.1

Comparison 5 Orlistat: GI Adverse Events, Outcome 1 Orlistat: Overall GI Adverse Events (Absolute % Difference).

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Analysis 5.2

Comparison 5 Orlistat: GI Adverse Events, Outcome 2 Orlistat: Fecal Incontinence (Absolute % Difference).

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Analysis 5.3

Comparison 5 Orlistat: GI Adverse Events, Outcome 3 Orlistat: Discontinuation Due to GI Side Effects (Absolute % Difference).

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Analysis 6.1

Comparison 6 Sibutramine: Anthropometric Outcomes, Outcome 1 Sibutramine: Change in Weight (%).

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Analysis 6.2

Comparison 6 Sibutramine: Anthropometric Outcomes, Outcome 2 Sibutramine: Change in Weight (kg).

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Analysis 6.3

Comparison 6 Sibutramine: Anthropometric Outcomes, Outcome 3 Sibutramine: 5% Responders (absolute % difference).

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Analysis 6.4

Comparison 6 Sibutramine: Anthropometric Outcomes, Outcome 4 Sibutramine: 10% Responders (absolute % difference).

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Analysis 6.5

Comparison 6 Sibutramine: Anthropometric Outcomes, Outcome 5 Sibutramine: Change in Waist Circumference (cm).

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Analysis 6.6

Comparison 6 Sibutramine: Anthropometric Outcomes, Outcome 6 Sibutramine: Change in Body Mass Index (kg/m2).

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Analysis 6.7

Comparison 6 Sibutramine: Anthropometric Outcomes, Outcome 7 Sibutramine: Sensitivity Analysis According to Baseline CV Risk (Absolute Weight Loss).

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Analysis 6.8

Comparison 6 Sibutramine: Anthropometric Outcomes, Outcome 8 Sibutramine: Sensitivity Analysis According to Baseline CV Risk (% Weight Loss).

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Analysis 7.1

Comparison 7 Sibutramine: Change in Blood Pressure, Outcome 1 Sibutramine: Change in Systolic Blood Pressure (mm Hg).

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Analysis 7.2

Comparison 7 Sibutramine: Change in Blood Pressure, Outcome 2 Sibutramine: Change in Diastolic Blood Pressure (mm Hg).

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Analysis 8.1

Comparison 8 Sibutramine: Change in Lipid Parameters, Outcome 1 Sibutramine: Change in HDL cholesterol (mmol/L).

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Analysis 8.2

Comparison 8 Sibutramine: Change in Lipid Parameters, Outcome 2 Sibutramine: Change in Triglycerides (mmol/L).

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Analysis 9.1

Comparison 9 Sibutramine: Subgroup Analysis in Diabetes, Outcome 1 Change in Weight (%).

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Analysis 9.2

Comparison 9 Sibutramine: Subgroup Analysis in Diabetes, Outcome 2 Change in Weight (kg).

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Analysis 10.1

Comparison 10 Sibutramine: Change in Heart Rate, Outcome 1 Change in Heart Rate (beats/min).

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Analysis 11.1

Comparison 11 Rimonabant: Anthropometric Outcomes, Outcome 1 Rimonabant: Change in Weight (kg).

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Analysis 11.2

Comparison 11 Rimonabant: Anthropometric Outcomes, Outcome 2 Rimonabant: 5% Responders (absolute % difference).

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Analysis 11.3

Comparison 11 Rimonabant: Anthropometric Outcomes, Outcome 3 Rimonabant: 10% Responders (absolute % difference).

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Analysis 11.4

Comparison 11 Rimonabant: Anthropometric Outcomes, Outcome 4 Rimonabant: Change in Waist Circumference (cm).

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Analysis 12.1

Comparison 12 Rimonabant: Change in Blood Pressure, Outcome 1 Rimonabant: Change in Systolic Blood Pressure (mm Hg).

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Analysis 12.2

Comparison 12 Rimonabant: Change in Blood Pressure, Outcome 2 Rimonabant: Change in Diastolic Blood Pressure (mm Hg).

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Analysis 13.1

Comparison 13 Rimonabant: Change in Lipid Parameters, Outcome 1 Rimonabant: Change in Total Cholesterol (mmol/L).

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Analysis 13.2

Comparison 13 Rimonabant: Change in Lipid Parameters, Outcome 2 Rimonabant: Change in LDL Cholesterol (mmol/L).

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Analysis 13.3

Comparison 13 Rimonabant: Change in Lipid Parameters, Outcome 3 Rimonabant: Change in HDL Cholesterol (mmol/L).

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Analysis 13.4

Comparison 13 Rimonabant: Change in Lipid Parameters, Outcome 4 Rimonabant: Change in Triglycerides (mmol/L).

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Analysis 14.1

Comparison 14 Rimonabant: Adverse Events, Outcome 1 Rimonabant: Discontinuation due to Adverse Event (Absolute % Difference).

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Analysis 14.2

Comparison 14 Rimonabant: Adverse Events, Outcome 2 Rimonabant: Serious Adverse Event (Absolute % Difference).

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Analysis 14.3

Comparison 14 Rimonabant: Adverse Events, Outcome 3 Rimonabant: Psychiatric Disorders (Absolute % Difference).

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Comparison 1. Orlistat: Anthropometric Outcomes

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Orlistat: Change in Weight (%) Show forest plot	13	6196	Mean Difference (IV, Random, 95% CI)	‐2.93 [‐3.35, ‐2.50]

2 Orlistat: Change in Weight (kg) Show forest plot	14	9457	Mean Difference (IV, Random, 95% CI)	‐2.87 [‐3.21, ‐2.53]

3 Orlistat: 5% Responders (absolute % difference) Show forest plot	14	9389	Risk Difference (M‐H, Random, 95% CI)	0.21 [0.18, 0.24]

4 Orlistat: 10% Responders (absolute % difference) Show forest plot	13	8857	Risk Difference (M‐H, Random, 95% CI)	0.12 [0.09, 0.14]

5 Orlistat: Change in Waist Circumference (cm) Show forest plot	9	4631	Mean Difference (IV, Random, 95% CI)	‐2.06 [‐2.86, ‐1.26]

6 Orlistat: Change in Body Mass Index (kg/m2) Show forest plot	3	1276	Mean Difference (IV, Random, 95% CI)	‐1.05 [‐1.40, ‐0.71]

7 Orlistat: Sensitivity Analysis According to Baseline CV Risk (Absolute Weight Loss) Show forest plot	15	9833	Mean Difference (IV, Random, 95% CI)	‐2.75 [‐3.13, ‐2.36]

7.1 Change in Weight in Lower Risk Population (kg)	7	6655	Mean Difference (IV, Random, 95% CI)	‐3.00 [‐3.59, ‐2.41]
7.2 Change in Weight in Higher Risk Population (kg)	8	3178	Mean Difference (IV, Random, 95% CI)	‐2.59 [‐3.16, ‐2.02]
8 Orlistat: Sensitivity Analysis According to Baseline CV Risk (% Weight Loss) Show forest plot	13	6196	Mean Difference (IV, Random, 95% CI)	‐2.93 [‐3.35, ‐2.50]

8.1 Change in Weight in Lower Risk Population (%)	6	3378	Mean Difference (IV, Random, 95% CI)	‐3.42 [‐4.01, ‐2.83]
8.2 Change in Weight in Higher Risk Population (%)	7	2818	Mean Difference (IV, Random, 95% CI)	‐2.68 [‐3.25, ‐2.11]

Comparison 1. Orlistat: Anthropometric Outcomes

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Comparison 2. Orlistat: Change in Blood Pressure

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Orlistat: Change in Systolic Blood Pressure (mm Hg) Show forest plot	13	6965	Mean Difference (IV, Random, 95% CI)	‐1.52 [‐2.19, ‐0.86]

2 Orlistat: Change in Diastolic Blood Pressure (mm Hg) Show forest plot	12	8322	Mean Difference (IV, Random, 95% CI)	‐1.38 [‐2.03, ‐0.74]

Comparison 2. Orlistat: Change in Blood Pressure

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Comparison 3. Orlistat: Change in Lipid Parameters

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Orlistat: Change in Total Cholesterol Levels Show forest plot	13	5206	Mean Difference (IV, Random, 95% CI)	‐0.32 [‐0.37, ‐0.28]

2 Orlistat: Change in LDL cholesterol levels Show forest plot	13	5206	Mean Difference (IV, Random, 95% CI)	‐0.26 [‐0.30, ‐0.22]

3 Orlistat: Change in HDL cholesterol Levels Show forest plot	11	4152	Mean Difference (IV, Random, 95% CI)	‐0.03 [‐0.04, ‐0.02]

4 Orlistat: Change in Triglyceride Levels Show forest plot	11	4456	Mean Difference (IV, Random, 95% CI)	‐0.03 [‐0.12, 0.07]

Comparison 3. Orlistat: Change in Lipid Parameters

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Comparison 4. Orlistat: Subgroup Analysis in Diabetes

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in Weight (%) Show forest plot	5	1678	Mean Difference (IV, Random, 95% CI)	‐2.61 [‐3.06, ‐2.16]

2 Change in Weight (kg) Show forest plot	4	1737	Mean Difference (IV, Random, 95% CI)	‐2.30 [‐1.00, ‐1.60]

3 Change in Fasting Glucose Levels (mmol/L) Show forest plot	5	1678	Mean Difference (IV, Random, 95% CI)	‐1.03 [‐1.49, ‐0.57]

4 Orlistat: Change in HgbA1c (%) Show forest plot	5	1678	Mean Difference (IV, Random, 95% CI)	‐0.38 [‐0.59, ‐0.18]

Comparison 4. Orlistat: Subgroup Analysis in Diabetes

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Comparison 5. Orlistat: GI Adverse Events

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Orlistat: Overall GI Adverse Events (Absolute % Difference) Show forest plot	14	8938	Risk Difference (M‐H, Random, 95% CI)	0.24 [0.20, 0.29]

2 Orlistat: Fecal Incontinence (Absolute % Difference) Show forest plot	4	1636	Risk Difference (M‐H, Random, 95% CI)	0.06 [0.05, 0.08]

3 Orlistat: Discontinuation Due to GI Side Effects (Absolute % Difference) Show forest plot	12	5994	Risk Difference (M‐H, Random, 95% CI)	0.02 [0.01, 0.03]

Comparison 5. Orlistat: GI Adverse Events

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Comparison 6. Sibutramine: Anthropometric Outcomes

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Sibutramine: Change in Weight (%) Show forest plot	8	1725	Mean Difference (IV, Random, 95% CI)	‐4.34 [‐5.01, ‐3.67]

1.1 Weight Loss Studies	7	1536	Mean Difference (IV, Random, 95% CI)	‐4.54 [‐5.11, ‐3.96]
1.2 Weight Maintenance Studies	1	189	Mean Difference (IV, Random, 95% CI)	‐2.40 [‐4.44, ‐0.36]
2 Sibutramine: Change in Weight (kg) Show forest plot	10	2348	Mean Difference (IV, Random, 95% CI)	‐4.16 [‐4.73, ‐3.59]

2.1 Weight Loss Studies	7	1536	Mean Difference (IV, Random, 95% CI)	‐4.20 [‐4.77, ‐3.64]
2.2 Weight Maintenance Studies	3	812	Mean Difference (IV, Random, 95% CI)	‐4.01 [‐5.73, ‐2.28]
3 Sibutramine: 5% Responders (absolute % difference) Show forest plot	7	1464	Risk Difference (M‐H, Random, 95% CI)	0.32 [0.27, 0.37]

3.1 Weight Loss Studies	6	1304	Risk Difference (M‐H, Random, 95% CI)	0.32 [0.27, 0.38]
3.2 Weight Maintenance Studies	1	160	Risk Difference (M‐H, Random, 95% CI)	0.31 [0.18, 0.45]
4 Sibutramine: 10% Responders (absolute % difference) Show forest plot	7	1464	Risk Difference (M‐H, Random, 95% CI)	0.18 [0.11, 0.25]

4.1 Weight Loss Studies	6	1304	Risk Difference (M‐H, Random, 95% CI)	0.17 [0.10, 0.23]
4.2 Weight Maintenance Studies	1	160	Risk Difference (M‐H, Random, 95% CI)	0.31 [0.16, 0.45]
5 Sibutramine: Change in Waist Circumference (cm) Show forest plot	8	1837	Mean Difference (IV, Random, 95% CI)	‐3.99 [‐4.70, ‐3.28]

5.1 Weight Loss Studies	6	1237	Mean Difference (IV, Random, 95% CI)	‐3.97 [‐4.92, ‐3.03]
5.2 Weight Maintenance Studies	2	600	Mean Difference (IV, Random, 95% CI)	‐4.11 [‐5.52, ‐2.70]
6 Sibutramine: Change in Body Mass Index (kg/m2) Show forest plot	5	956	Mean Difference (IV, Random, 95% CI)	‐1.54 [‐1.79, ‐1.30]

7 Sibutramine: Sensitivity Analysis According to Baseline CV Risk (Absolute Weight Loss) Show forest plot	10	2348	Mean Difference (IV, Random, 95% CI)	‐4.16 [‐4.73, ‐3.59]

7.1 Change in Weight in Lower Risk Population (kg)	5	1470	Mean Difference (IV, Random, 95% CI)	‐3.99 [‐5.04, ‐2.95]
7.2 Change in Weight in Higher Risk Population (kg)	5	878	Mean Difference (IV, Random, 95% CI)	‐4.28 [‐4.97, ‐3.58]
8 Sibutramine: Sensitivity Analysis According to Baseline CV Risk (% Weight Loss) Show forest plot	8	1725	Mean Difference (IV, Random, 95% CI)	‐4.34 [‐5.01, ‐3.67]

8.1 Change in Weight in Lower Risk Population (%)	3	847	Mean Difference (IV, Random, 95% CI)	‐3.87 [‐5.68, ‐2.06]
8.2 Change in Weight in Higher Risk Population (%)	5	878	Mean Difference (IV, Random, 95% CI)	‐4.53 [‐5.23, ‐3.83]

Comparison 6. Sibutramine: Anthropometric Outcomes

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Comparison 7. Sibutramine: Change in Blood Pressure

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Sibutramine: Change in Systolic Blood Pressure (mm Hg) Show forest plot	7	1906	Mean Difference (IV, Random, 95% CI)	1.69 [0.11, 3.28]

1.1 Weight Loss Studies	6	1442	Mean Difference (IV, Random, 95% CI)	1.02 [‐0.39, 2.43]
1.2 Weight Maintenance Studies	1	464	Mean Difference (IV, Random, 95% CI)	4.3 [1.57, 7.03]
2 Sibutramine: Change in Diastolic Blood Pressure (mm Hg) Show forest plot	7	1906	Mean Difference (IV, Random, 95% CI)	2.42 [1.51, 3.32]

2.1 Weight Loss Studies	6	1442	Mean Difference (IV, Random, 95% CI)	2.15 [1.26, 3.03]
2.2 Weight Maintenance Studies	1	464	Mean Difference (IV, Random, 95% CI)	3.9 [1.98, 5.82]

Comparison 7. Sibutramine: Change in Blood Pressure

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Comparison 8. Sibutramine: Change in Lipid Parameters

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Sibutramine: Change in HDL cholesterol (mmol/L) Show forest plot	5	977	Mean Difference (IV, Random, 95% CI)	0.04 [0.01, 0.08]

1.1 Weight Loss Studies	4	818	Mean Difference (IV, Random, 95% CI)	0.06 [0.03, 0.10]
1.2 Weight Maintenance Studies	1	159	Mean Difference (IV, Random, 95% CI)	0.01 [0.00, 0.02]
2 Sibutramine: Change in Triglycerides (mmol/L) Show forest plot	4	785	Mean Difference (IV, Random, 95% CI)	‐0.18 [‐0.30, ‐0.07]

2.1 Weight Loss Studies	3	626	Mean Difference (IV, Random, 95% CI)	‐0.21 [‐0.40, ‐0.03]
2.2 Weight Maintenance Studies	1	159	Mean Difference (IV, Random, 95% CI)	‐0.16 [‐0.31, ‐0.01]

Comparison 8. Sibutramine: Change in Lipid Parameters

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Comparison 9. Sibutramine: Subgroup Analysis in Diabetes

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in Weight (%) Show forest plot	3	450	Mean Difference (IV, Random, 95% CI)	‐4.99 [‐6.20, ‐3.78]

2 Change in Weight (kg) Show forest plot	3	450	Mean Difference (IV, Random, 95% CI)	‐4.91 [‐6.18, ‐3.64]

Comparison 9. Sibutramine: Subgroup Analysis in Diabetes

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Comparison 10. Sibutramine: Change in Heart Rate

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Change in Heart Rate (beats/min) Show forest plot	7	1658	Mean Difference (IV, Random, 95% CI)	4.53 [3.49, 5.57]

1.1 Weight Loss Studies	5	1035	Mean Difference (IV, Random, 95% CI)	4.16 [2.86, 5.45]
1.2 Weight Maintenance Studies	2	623	Mean Difference (IV, Random, 95% CI)	5.44 [2.94, 7.94]

Comparison 10. Sibutramine: Change in Heart Rate

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Comparison 11. Rimonabant: Anthropometric Outcomes

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Rimonabant: Change in Weight (kg) Show forest plot	4	4099	Mean Difference (IV, Random, 95% CI)	‐4.67 [‐5.26, ‐4.07]

2 Rimonabant: 5% Responders (absolute % difference) Show forest plot	4	4099	Risk Difference (M‐H, Random, 95% CI)	0.33 [0.29, 0.37]

3 Rimonabant: 10% Responders (absolute % difference) Show forest plot	4	4099	Risk Difference (M‐H, Random, 95% CI)	0.19 [0.15, 0.23]

4 Rimonabant: Change in Waist Circumference (cm) Show forest plot	4	4098	Mean Difference (IV, Random, 95% CI)	‐3.89 [‐4.47, ‐3.30]

Comparison 11. Rimonabant: Anthropometric Outcomes

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Comparison 12. Rimonabant: Change in Blood Pressure

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Rimonabant: Change in Systolic Blood Pressure (mm Hg) Show forest plot	3	2273	Mean Difference (IV, Random, 95% CI)	‐1.78 [‐2.81, ‐0.76]

2 Rimonabant: Change in Diastolic Blood Pressure (mm Hg) Show forest plot	3	2273	Mean Difference (IV, Random, 95% CI)	‐1.23 [‐1.93, ‐0.54]

Comparison 12. Rimonabant: Change in Blood Pressure

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Comparison 13. Rimonabant: Change in Lipid Parameters

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Rimonabant: Change in Total Cholesterol (mmol/L) Show forest plot	3	2223	Mean Difference (IV, Random, 95% CI)	‐0.04 [‐0.11, 0.03]

2 Rimonabant: Change in LDL Cholesterol (mmol/L) Show forest plot	3	2223	Mean Difference (IV, Random, 95% CI)	‐0.05 [‐0.12, 0.01]

3 Rimonabant: Change in HDL Cholesterol (mmol/L) Show forest plot	4	4050	Mean Difference (IV, Random, 95% CI)	0.10 [0.08, 0.11]

4 Rimonabant: Change in Triglycerides (mmol/L) Show forest plot	4	4049	Mean Difference (IV, Random, 95% CI)	‐0.24 [‐0.30, ‐0.17]

Comparison 13. Rimonabant: Change in Lipid Parameters

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Comparison 14. Rimonabant: Adverse Events

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Rimonabant: Discontinuation due to Adverse Event (Absolute % Difference) Show forest plot	4	4105	Risk Difference (M‐H, Random, 95% CI)	0.06 [0.05, 0.08]

2 Rimonabant: Serious Adverse Event (Absolute % Difference) Show forest plot	4	4105	Risk Difference (M‐H, Random, 95% CI)	0.02 [0.00, 0.03]

3 Rimonabant: Psychiatric Disorders (Absolute % Difference) Show forest plot	4	4105	Risk Difference (M‐H, Random, 95% CI)	0.03 [0.02, 0.05]

Comparison 14. Rimonabant: Adverse Events

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