Plain Language Summary
Introduction
Methods
Study Design
Data Sources and Searches
Study Selection
Data Extraction and Quality Assessment
Data Synthesis and Analysis
Results
Literature Search
Study Characteristics
First author and title of original trial | Type of treatment | Treatment indication | Sample size (pregnant women) | Dose of metformin (mg/day) and dose of placebo or insulin | Number of women requiring additional insulin | Age (years ± SD) | Pre- or early pregnancy BMI (kg/m2 ± SD) | First author and year of publication of follow-up studies |
---|---|---|---|---|---|---|---|---|
Rowan, J.A. Metformin versus insulin for the treatment of gestational diabetes [38] | Metformin | GDMa | 363 | 500–2500 | 168 (46.3%) | 33.5 ± 5.4 | 32.2 ± 8.2 | Battin 2017 [26] Rowan 2011 [25] Wouldes 2016 [27] Rowan 2018 [33] |
Insulin | GDMa | 370 | Usual practice | N/A | 33.0 ± 5.1 | 31.9 ± 7.6 | ||
Vanky, E. Metformin versus placebo from first trimester to delivery in polycystic ovary syndrome: a randomized, controlled multicenter study [37] | Metformin | PCOS | 135 | 1000–2000 | 0 (0%) | 29.6 ± 4.4 | 29.5 ± 7.0 | Carlsen 2012 [28] Hanem 2018 [34]d |
Placebo | PCOS | 138 | 1000–2000 | 3 (2%) | 29.2 ± 4.4 | 28.5 ± 7.2 | ||
Ijäs, H. Metformin should be considered in the treatment of gestational diabetes: a prospective randomised study [39] | Metformin | GDMb | 47 | 750–2250 | 15 (32%) | 32.3 ± 5.6 | 31.5 ± 6.5 | Ijäs 2014 [29] |
Insulin | GDMb | 50 | Usual practice | N/A | 31.7 ± 6.1 | 30.8 ± 5.4 | ||
Tertti, K. Metformin vs. insulin in gestational diabetes. A randomized study characterizing metformin patients needing additional insulin [40] | Metformin | GDMc | 110 | 500–2000 | 23 (20.9%) | 31.9 ± 5.0 | 29.4 ± 5.9 | Tertti 2015 [30] Tertti 2016 [31] |
Insulin | GDMc | 107 | Usual practice | N/A | 32.1 ± 5.4 | 28.9 ± 4.7 | ||
Vanky, E. Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study [41] | Metformin | PCOS | 18 | 850–1700 | 0 (0%) | 28.9 ± 4.8 | 32.1 ± 6.1 | Rø 2012 [32] Hanem 2018 [34]d |
Placebo | PCOS | 22 | Identical as metformin | 2 (9%) | 28.3 ± 3.7 | 29.3 ± 8.0 |
Name first author and article of original trial | First author and year of publication | Origin of population and duration of follow-up RCT (years) | Maternal treatment during gestation | Number of offspring | Male (%) | Gestational age at randomisation (weeks; mean ± SD) | Age of offspring (months; mean ± SD) | |
---|---|---|---|---|---|---|---|---|
Rowan, J.A. Metformin versus insulin for the treatment of gestational diabetes [38] | Battin 2015 [26] | Australia, New Zealand 2004–2008 | Metformin | 83 | 48.2 | 20–33b | 29 (22–38)d | |
Insulin | 87 | 47.1 | 20–33b | |||||
Rowan 2011 [25] | Australia, New Zealand 2004–2008 | Metformin | 154 | 56 | 30.4 ± 3.3 | 28.7 ± 3.6 | ||
Insulin | 164 | 48 | 30.0 ± 3.3 | 29.4 ± 3.8 | ||||
Rowan 2018 [33] | Australia, New Zealand 2009–2011 | Australia | Metformin | 58 | 60 | 31.3 ± 2.8 | 7.0 ± 1.0e | |
Insulin | 51 | 45 | 31.6 ± 2 | 7.4 ± 1.1e | ||||
New Zealand | Metformin | 45 | 62 | 29.9 ± 3.6 | 8.9 ± 0.5e | |||
Insulin | 54 | 52 | 29.5 ± 3.4 | 8.9 ± 0.4e | ||||
Wouldes 2016 [27] | Australia, New Zealand 2004–2008 | Australia | Metformin | 39 | 56 | 20–33 | 33.2 ± 1.9 | |
Insulin | 44 | 46 | 20–33b | 33.6 ± 1.4 | ||||
New Zealand | Metformin | 64 | 52 | 20–33b | 27.4 ± 2.5 | |||
Insulin | 64 | 45 | 20–33b | 27.3 ± 2.4 | ||||
Vanky, E. Metformin versus placebo from first trimester to delivery in polycystic ovary syndrome: a randomized, controlled multicenter study [37] | Carlsen 2012 [28] | Norway 2006–2010 | Metformin | 102 | 49 | 10.6 (5–12)c | ≈ 12 | |
Placebo | 94 | 47 | 10.7 (5–12)c | |||||
Hanem 2018 [34]a | Norway 2014–2016 | Metformin | 81 | Not given | 5–12b | ≈ 1 and 4 | ||
Placebo | 79 | |||||||
Ijäs, H. Metformin should be considered in the treatment of gestational diabetes: a prospective randomised study [39] | Ijäs 2014 [29] | Finland 2007–2011 | Metformin | 45 | 47 | 30.0 ± 4.5 | ≈ 6, 12 and 18 | |
Insulin | 48 | 46 | 30.4 ± 4.1 | |||||
Tertti, K. Metformin vs. insulin in gestational diabetes. A randomized study characterizing metformin patients needing additional insulin [40] | Tertti 2015 [30] | Finland 2008–2012 | Metformin | 75 | 47 | 30.3 ± 2.0 | 24 (23–24)c | |
Insulin | 71 | 46 | 30.4 ± 1.8 | 24 (23–24)c | ||||
Tertti 2016 [31] | Finland 2013–2014 | Metformin | 25 | 100 | 22–34b | 60.4 ± 17.0 | ||
Insulin | 27 | 100 | 22–34b | 60.7 ± 15.4 | ||||
Vanky, E. Metformin reduces pregnancy complications without affecting androgen levels in pregnant polycystic ovary syndrome women: results of a randomized study [41] | Rø 2012 [32] | Norway 2008–2011 | Metformin | 12 | 67 | 5–12b | 8.2 ± 0.6b | |
Placebo | 13 | 23 | 5–12b | 8.1 ± 0.8b |