Scolaris Content Display Scolaris Content Display

Study flow diagram
Figures and Tables -
Figure 1

Study flow diagram

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
Figures and Tables -
Figure 2

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

Risk of bias summary: review authors' judgements about each risk of bias item for each included study
Figures and Tables -
Figure 3

Risk of bias summary: review authors' judgements about each risk of bias item for each included study

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 1 Hypertensive disorders of pregnancy: pre‐eclampsia.
Figures and Tables -
Analysis 1.1

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 1 Hypertensive disorders of pregnancy: pre‐eclampsia.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 2 Hypertensive disorders of pregnancy: pregnancy‐induced hypertension.
Figures and Tables -
Analysis 1.2

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 2 Hypertensive disorders of pregnancy: pregnancy‐induced hypertension.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 3 Caesarean section.
Figures and Tables -
Analysis 1.3

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 3 Caesarean section.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 4 Large‐for‐gestational age.
Figures and Tables -
Analysis 1.4

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 4 Large‐for‐gestational age.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 5 Perinatal mortality.
Figures and Tables -
Analysis 1.5

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 5 Perinatal mortality.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 6 Miscarriage.
Figures and Tables -
Analysis 1.6

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 6 Miscarriage.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 7 Induction of labour.
Figures and Tables -
Analysis 1.7

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 7 Induction of labour.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 8 Postpartum haemorrhage.
Figures and Tables -
Analysis 1.8

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 8 Postpartum haemorrhage.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 9 Weight gain in pregnancy (kg).
Figures and Tables -
Analysis 1.9

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 9 Weight gain in pregnancy (kg).

Study

Metformin (N=9)

Insulin (N=6)

Hickman 2013

Median (IQR): 3.16 (2.88, 4.50)

Median (IQR): 10.78 (8.15, 14.42)

Figures and Tables -
Analysis 1.10

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 10 Weight gain in pregnancy (kg).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 11 Adherence to the intervention (how often did you forget to take treatment?).
Figures and Tables -
Analysis 1.11

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 11 Adherence to the intervention (how often did you forget to take treatment?).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 12 Adherence to the intervention.
Figures and Tables -
Analysis 1.12

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 12 Adherence to the intervention.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 13 Views of the intervention (which medication would you choose in next pregnancy?).
Figures and Tables -
Analysis 1.13

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 13 Views of the intervention (which medication would you choose in next pregnancy?).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 14 Views of the intervention (which part of diabetes treatment was easy?).
Figures and Tables -
Analysis 1.14

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 14 Views of the intervention (which part of diabetes treatment was easy?).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 15 Views of the intervention (which part of diabetes treatment was difficult?).
Figures and Tables -
Analysis 1.15

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 15 Views of the intervention (which part of diabetes treatment was difficult?).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 16 Views of the intervention (choose same treatment in the future).
Figures and Tables -
Analysis 1.16

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 16 Views of the intervention (choose same treatment in the future).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 17 Adverse effects of the intervention (side effects).
Figures and Tables -
Analysis 1.17

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 17 Adverse effects of the intervention (side effects).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 18 Breastfeeding.
Figures and Tables -
Analysis 1.18

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 18 Breastfeeding.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 19 Glycaemic control (fasting blood glucose throughout pregnancy (mg/dL)).
Figures and Tables -
Analysis 1.19

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 19 Glycaemic control (fasting blood glucose throughout pregnancy (mg/dL)).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 20 Glycaemic control (random blood glucose throughout pregnancy (mg/dL)).
Figures and Tables -
Analysis 1.20

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 20 Glycaemic control (random blood glucose throughout pregnancy (mg/dL)).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 21 Glycaemic control (change in HbA1c from enrolment to third trimester/birth (%)).
Figures and Tables -
Analysis 1.21

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 21 Glycaemic control (change in HbA1c from enrolment to third trimester/birth (%)).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 22 Glycaemic control (HbA1c < 7% at third trimester/birth).
Figures and Tables -
Analysis 1.22

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 22 Glycaemic control (HbA1c < 7% at third trimester/birth).

Study

Metformin (N=8)

Insulin (N=6)

Hickman 2013

HbA1c 2nd trimester (%)

Median (IQR): 5.55 (5.54, 5.70)

HbA1c 2nd trimester (%)

Median (IQR): 5.70 (5.35, 6.28)

Hickman 2013

HbA1c 3rd trimester (%)

Median (IQR): 5.85 (5.73, 6.00)

HbA1c 3rd trimester (%)

Median (IQR): 5.85 (5.53, 6.55)

Hickman 2013

Delivery glucose (mg/dL)

Median (IQR): 96.00 (92.00, 113.00)

Delivery glucose (mg/dL)

Median (IQR): 127.50 (109.25, 122.00)

Hickman 2013

Postpartum fasting glucose (mg/dL)

Median (IQR): 97.50 (78.50, 108.75)

Postpartum fasting glucose (mg/dL)

Median (IQR): 125.50 (109.75, 136.75)

Figures and Tables -
Analysis 1.23

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 23 Glycaemic control.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 24 Congenital anomaly (major malformations).
Figures and Tables -
Analysis 1.24

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 24 Congenital anomaly (major malformations).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 25 Stillbirth.
Figures and Tables -
Analysis 1.25

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 25 Stillbirth.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 26 Neonatal mortality.
Figures and Tables -
Analysis 1.26

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 26 Neonatal mortality.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 27 Gestational age at birth (weeks).
Figures and Tables -
Analysis 1.27

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 27 Gestational age at birth (weeks).

Study

Metformin

Insulin

P value

Hickman 2013

Median (IQR): 38.40 (37.10, 38.86)

N=9

Median (IQR): 37.50 (35.79, 38.00)

N=6

Refuerzo 2015

Median (range): 37 (35‐40)

N=8

Median (range): 37 (35‐41)

N=13

0.977

Figures and Tables -
Analysis 1.28

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 28 Gestational age at birth (weeks).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 29 Preterm birth.
Figures and Tables -
Analysis 1.29

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 29 Preterm birth.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 30 Apgar score < 7 at 5 minutes.
Figures and Tables -
Analysis 1.30

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 30 Apgar score < 7 at 5 minutes.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 31 Macrosomia (> 4000 g).
Figures and Tables -
Analysis 1.31

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 31 Macrosomia (> 4000 g).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 32 Small‐for‐gestational age.
Figures and Tables -
Analysis 1.32

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 32 Small‐for‐gestational age.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 33 Birthweight (kg).
Figures and Tables -
Analysis 1.33

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 33 Birthweight (kg).

Study

Metformin (N=8)

Insulin (N=6)

Hickman 2013

Median (IQR): 3071.50 (2978.75, 3237.75)

Median (IQR): 3295.50 (2964.25, 3566.75)

Figures and Tables -
Analysis 1.34

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 34 Birthweight (g).

Study

Metformin (N=8)

Insulin (N=6)

Hickman 2013

Median (IQR): 33.50 (32.48, 34.63)

Median (IQR): 33.50 (32.25, 34.75)

Figures and Tables -
Analysis 1.35

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 35 Head circumference (cm).

Study

Metformin (N=8)

Insulin (N=6)

Hickman 2013

Median (IQR): 49.00 (48.07, 50.53)

Median (IQR): 49.50 (48.45, 52.25)

Figures and Tables -
Analysis 1.36

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 36 Length (cm).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 37 Shoulder dystocia.
Figures and Tables -
Analysis 1.37

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 37 Shoulder dystocia.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 38 Bone fracture (birth injury/birth trauma with clavicle fracture).
Figures and Tables -
Analysis 1.38

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 38 Bone fracture (birth injury/birth trauma with clavicle fracture).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 39 Respiratory distress syndrome.
Figures and Tables -
Analysis 1.39

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 39 Respiratory distress syndrome.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 40 Hypoglycaemia.
Figures and Tables -
Analysis 1.40

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 40 Hypoglycaemia.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 41 Hyperbilirubinaemia (jaundice).
Figures and Tables -
Analysis 1.41

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 41 Hyperbilirubinaemia (jaundice).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 42 Infection (sepsis).
Figures and Tables -
Analysis 1.42

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 42 Infection (sepsis).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 43 Relevant biomarkers (blood glucose level at birth (mg/dL)).
Figures and Tables -
Analysis 1.43

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 43 Relevant biomarkers (blood glucose level at birth (mg/dL)).

Study

Metformin (N=6)

Insulin (N=4)

Hickman 2013

Median (IQR): 1.25 (0.92, 1.65)

Median (IQR): 3.95 (2.78, 5.13)

Figures and Tables -
Analysis 1.44

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 44 Relevant biomarker (cord C peptide).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 45 Number of antenatal admissions.
Figures and Tables -
Analysis 1.45

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 45 Number of antenatal admissions.

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 46 Neonatal intensive care unit admission.
Figures and Tables -
Analysis 1.46

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 46 Neonatal intensive care unit admission.

Study

Metformin

Insulin

P value

Refuerzo 2015

Median (range): 3 (1‐8)

N=8

Median (range): 2 (1‐12)

N=13

0.697

Figures and Tables -
Analysis 1.47

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 47 Length of postnatal stay (baby) (days).

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 48 Cost of maternal care (total cost of treatment throughout pregnancy (USD)).
Figures and Tables -
Analysis 1.48

Comparison 1 Oral anti‐diabetic agent (metformin) versus insulin, Outcome 48 Cost of maternal care (total cost of treatment throughout pregnancy (USD)).

Summary of findings for the main comparison. Maternal outcomes: oral anti‐diabetic agent (metformin) compared with insulin for women with established type 2 diabetes mellitus

Maternal outcomes: oral anti‐diabetic agent (metformin) compared with insulin for women with established type 2 diabetes mellitus

Patient or population: women with type 2 diabetes
Setting: USA (2 RCTs), Pakistan (1 RCT)
Intervention: oral anti‐diabetic agent (metformin)
Comparison: insulin

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with insulin

Risk with oral anti‐diabetic (metformin)

Hypertensive disorders of pregnancy: pre‐eclampsia

Study population

RR 0.63
(0.33 to 1.20)

227
(2 RCTs)

⊕⊝⊝⊝
VERY LOW 1,2

186 per 1000

117 per 1000
(61 to 223)

Hypertensive disorders of pregnancy: pregnancy‐induced hypertension

Study population

RR 0.58
(0.37 to 0.91)

206
(1 RCT)

⊕⊕⊝⊝
LOW 3

360 per 1000

209 per 1000
(133 to 328)

Caesarean section

Study population

RR 0.73
(0.61 to 0.88)

241
(3 RCTs)

⊕⊕⊝⊝
LOW 1

765 per 1000

558 per 1000
(466 to 673)

Induction of labour

Study population

RR 1.42
(0.62 to 3.28)

35
(2 RCTs)

⊕⊝⊝⊝
VERY LOW 2,4

316 per 1000

448 per 1000
(196 to 1000)

Perineal trauma

Study population

(0 RCTs)

None of the included RCTs reported this outcome

See comment

See comment

Postnatal depression

Study population

(0 RCTs)

None of the included RCTs reported these outcomes

See comment

See comment

Postnatal weight retention

Study population

(0 RCTs)

None of the included RCTs reported these outcomes

See comment

See comment

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Study limitations (‐2): most of the weight in this analysis was from 1 RCT with very serious design limitations

2 Imprecision (‐2): wide 95% CI crossing the line of no effect and small sample sizes of RCTs

3 Study limitations (‐2): 1 RCT with very serious design limitations contributed data

4 Study limitations (‐1): 2 RCTs with design limitations contributed data

Figures and Tables -
Summary of findings for the main comparison. Maternal outcomes: oral anti‐diabetic agent (metformin) compared with insulin for women with established type 2 diabetes mellitus
Summary of findings 2. Infant outcomes: oral anti‐diabetic agent (metformin) compared with insulin for women with established type 2 diabetes mellitus

Infant outcomes: oral anti‐diabetic (metformin) compared with insulin for women with established diabetes

Patient or population: women with type 2 diabetes mellitus
Setting: USA (2 RCTs) and Pakistan (1 RCT)
Intervention: oral anti‐diabetic agent (metformin)
Comparison: insulin

Outcomes

Anticipated absolute effects* (95% CI)

Relative effect
(95% CI)

№ of participants
(studies)

Quality of the evidence
(GRADE)

Comments

Risk with insulin

Risk with oral anti‐diabetic (metformin)

Large‐for‐gestational age

Study population

RR 1.12
(0.73 to 1.72)

206
(1 RCT)

⊕⊝⊝⊝
VERY LOW 1,2

270 per 1000

302 per 1000
(197 to 464)

Perinatal mortality

Study population

220
(2 RCTs)

⊕⊝⊝⊝
VERY LOW 3,4

No perinatal mortality in the 2 RCTs

See comment

See comment

Hypoglycaemia

Study population

RR 0.34
(0.18 to 0.62)

241
(3 RCTs)

⊕⊝⊝⊝
VERY LOW 5,6

277 per 1000

94 per 1000
(50 to 172)

Neonatal mortality or morbidity composite

Study population

(0 studies)

None of the included RCTs reported this outcome

See comment

See comment

Childhood/adulthood neurosensory disability

Study population

(0 studies)

None of the included RCTs reported this outcome

See comment

See comment

Childhood/adulthood adiposity

Study population

(0 studies)

None of the included RCTs reported this outcome

See comment

See comment

Childhood/adulthood diabetes

Study population

(0 studies)

None of the included RCTs reported this outcome

See comment

See comment

*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RCT: randomised controlled trial; RR: risk ratio

GRADE Working Group grades of evidence
High quality: We are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect
Very low quality: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

1 Study limitations (‐2): 1 RCT with very serious design limitations contributed data

2 Imprecision (‐2): wide 95% CI crossing the line of no effect and small sample size of RCT

3 Study limitations (‐1): 2 RCTs with design limitations contributed data

4 Imprecision (‐2): no events

5 Study limitations (‐2): most of the weight in this analysis was from 1 RCT with very serious design limitations

6 Imprecision (‐1): small sample sizes of RCTs

Figures and Tables -
Summary of findings 2. Infant outcomes: oral anti‐diabetic agent (metformin) compared with insulin for women with established type 2 diabetes mellitus
Comparison 1. Oral anti‐diabetic agent (metformin) versus insulin

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Hypertensive disorders of pregnancy: pre‐eclampsia Show forest plot

2

227

Risk Ratio (M‐H, Fixed, 95% CI)

0.63 [0.33, 1.20]

2 Hypertensive disorders of pregnancy: pregnancy‐induced hypertension Show forest plot

1

206

Risk Ratio (M‐H, Fixed, 95% CI)

0.58 [0.37, 0.91]

3 Caesarean section Show forest plot

3

241

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.61, 0.88]

4 Large‐for‐gestational age Show forest plot

1

206

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.73, 1.72]

5 Perinatal mortality Show forest plot

2

220

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

6 Miscarriage Show forest plot

1

15

Risk Ratio (M‐H, Fixed, 95% CI)

2.1 [0.10, 44.40]

7 Induction of labour Show forest plot

2

35

Risk Ratio (M‐H, Fixed, 95% CI)

1.42 [0.62, 3.28]

8 Postpartum haemorrhage Show forest plot

1

14

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

9 Weight gain in pregnancy (kg) Show forest plot

1

206

Mean Difference (IV, Fixed, 95% CI)

‐1.30 [‐1.57, ‐1.03]

10 Weight gain in pregnancy (kg) Show forest plot

Other data

No numeric data

11 Adherence to the intervention (how often did you forget to take treatment?) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

11.1 Never or rarely

1

206

Risk Ratio (M‐H, Fixed, 95% CI)

1.37 [1.14, 1.64]

11.2 2 to 4 times/week

1

206

Risk Ratio (M‐H, Fixed, 95% CI)

0.45 [0.28, 0.72]

12 Adherence to the intervention Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

12.1 No missed appointments

1

15

Risk Ratio (M‐H, Fixed, 95% CI)

2.0 [0.59, 6.79]

12.2 Log book completed > 50%

1

15

Risk Ratio (M‐H, Fixed, 95% CI)

1.9 [0.89, 4.04]

13 Views of the intervention (which medication would you choose in next pregnancy?) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

13.1 Metformin

1

206

Risk Ratio (M‐H, Fixed, 95% CI)

7.70 [4.52, 13.14]

13.2 Insulin

1

206

Risk Ratio (M‐H, Fixed, 95% CI)

0.07 [0.03, 0.19]

13.3 Not sure

1

206

Risk Ratio (M‐H, Fixed, 95% CI)

0.11 [0.04, 0.29]

14 Views of the intervention (which part of diabetes treatment was easy?) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

14.1 Doing finger pricks

1

206

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

14.2 Diet control

1

206

Risk Ratio (M‐H, Fixed, 95% CI)

0.02 [0.00, 0.30]

14.3 Drug treatment

1

206

Risk Ratio (M‐H, Fixed, 95% CI)

1.33 [1.19, 1.49]

15 Views of the intervention (which part of diabetes treatment was difficult?) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

15.1 Doing finger pricks

1

206

Risk Ratio (M‐H, Fixed, 95% CI)

3.46 [2.42, 4.95]

15.2 Diet control

1

206

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.31, 1.84]

15.3 Drug treatment

1

206

Risk Ratio (M‐H, Fixed, 95% CI)

0.14 [0.08, 0.26]

16 Views of the intervention (choose same treatment in the future) Show forest plot

1

11

Risk Ratio (M‐H, Fixed, 95% CI)

11.14 [0.78, 159.58]

17 Adverse effects of the intervention (side effects) Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

17.1 Gastrointestinal side effects resulting in dose limitation

1

206

Risk Ratio (M‐H, Fixed, 95% CI)

12.27 [0.70, 215.04]

17.2 Gastrointestinal side effects resulting in treatment cessation

1

206

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

17.3 Lactic acidosis

1

206

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

18 Breastfeeding Show forest plot

1

11

Risk Ratio (M‐H, Fixed, 95% CI)

1.59 [0.79, 3.23]

19 Glycaemic control (fasting blood glucose throughout pregnancy (mg/dL)) Show forest plot

1

206

Mean Difference (IV, Fixed, 95% CI)

0.01 [‐0.90, 0.92]

20 Glycaemic control (random blood glucose throughout pregnancy (mg/dL)) Show forest plot

1

206

Mean Difference (IV, Fixed, 95% CI)

‐0.22 [‐1.63, 1.19]

21 Glycaemic control (change in HbA1c from enrolment to third trimester/birth (%)) Show forest plot

1

21

Mean Difference (IV, Fixed, 95% CI)

‐0.48 [‐1.05, 0.09]

22 Glycaemic control (HbA1c < 7% at third trimester/birth) Show forest plot

1

18

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.76, 1.39]

23 Glycaemic control Show forest plot

Other data

No numeric data

24 Congenital anomaly (major malformations) Show forest plot

1

15

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

25 Stillbirth Show forest plot

2

220

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

26 Neonatal mortality Show forest plot

2

220

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

27 Gestational age at birth (weeks) Show forest plot

1

206

Mean Difference (IV, Fixed, 95% CI)

‐0.30 [‐0.66, 0.06]

28 Gestational age at birth (weeks) Show forest plot

Other data

No numeric data

29 Preterm birth Show forest plot

2

35

Risk Ratio (M‐H, Fixed, 95% CI)

0.42 [0.08, 2.30]

30 Apgar score < 7 at 5 minutes Show forest plot

1

14

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

31 Macrosomia (> 4000 g) Show forest plot

2

35

Risk Ratio (M‐H, Fixed, 95% CI)

0.37 [0.04, 3.10]

32 Small‐for‐gestational age Show forest plot

1

206

Risk Ratio (M‐H, Fixed, 95% CI)

8.49 [2.02, 35.66]

33 Birthweight (kg) Show forest plot

2

227

Mean Difference (IV, Fixed, 95% CI)

‐0.13 [‐0.29, 0.04]

34 Birthweight (g) Show forest plot

Other data

No numeric data

35 Head circumference (cm) Show forest plot

Other data

No numeric data

36 Length (cm) Show forest plot

Other data

No numeric data

37 Shoulder dystocia Show forest plot

2

35

Risk Ratio (M‐H, Fixed, 95% CI)

4.67 [0.21, 102.47]

38 Bone fracture (birth injury/birth trauma with clavicle fracture) Show forest plot

2

220

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.14, 6.57]

39 Respiratory distress syndrome Show forest plot

3

241

Risk Ratio (M‐H, Fixed, 95% CI)

0.52 [0.24, 1.13]

40 Hypoglycaemia Show forest plot

3

241

Risk Ratio (M‐H, Fixed, 95% CI)

0.34 [0.18, 0.62]

41 Hyperbilirubinaemia (jaundice) Show forest plot

2

220

Risk Ratio (M‐H, Fixed, 95% CI)

0.44 [0.24, 0.81]

42 Infection (sepsis) Show forest plot

2

220

Risk Ratio (M‐H, Fixed, 95% CI)

0.26 [0.08, 0.81]

43 Relevant biomarkers (blood glucose level at birth (mg/dL)) Show forest plot

1

206

Mean Difference (IV, Fixed, 95% CI)

3.57 [0.26, 6.88]

44 Relevant biomarker (cord C peptide) Show forest plot

Other data

No numeric data

45 Number of antenatal admissions Show forest plot

1

15

Risk Ratio (M‐H, Fixed, 95% CI)

0.22 [0.03, 1.66]

46 Neonatal intensive care unit admission Show forest plot

3

241

Risk Ratio (M‐H, Fixed, 95% CI)

0.37 [0.27, 0.52]

47 Length of postnatal stay (baby) (days) Show forest plot

Other data

No numeric data

48 Cost of maternal care (total cost of treatment throughout pregnancy (USD)) Show forest plot

1

206

Mean Difference (IV, Fixed, 95% CI)

‐65.3 [‐77.92, ‐52.68]

Figures and Tables -
Comparison 1. Oral anti‐diabetic agent (metformin) versus insulin