Metformin in pregnancy to avert gestational diabetes in women at high risk: Meta‐analysis of randomized controlled trials

Abstract

Previous randomized and observational studies on the efficacy of metformin in pregnancy to reduce incident gestational diabetes mellitus (GDM) in women at high risk (obesity, polycystic ovary syndrome [PCOS], or pregestational insulin resistance) have been conflicting and several groups are planning further randomized controlled trials (RCTs) to answer this question conclusively. This work assesses the efficacy of metformin in pregnancy to avert one outcome-incident GDM in women at high risk.We included RCTs comparing metformin with usual care or placebo controls in terms of incident GDM and recruiting women at high risk during early pregnancy. Eleven eligible trials enrolled 2370 adult women whose intervention arm consisted of metformin started at conception or before 20 weeks of gestation. Risk of GDM was similar in intervention compared with controls (risk ratio [RR] 1.03; 95% confidence interval [CI], 0.85-1.24). The data were of sufficient quality meeting the criteria for consistency and directness. We conclude that metformin does not contribute to averting the GDM outcome in women at high risk when initiated in pregnancy. The evidence provided by this synthesis affirms that further broad clinical trials investigating this question are no longer needed.

Association of Metformin With Pregnancy Outcomes in Women With Polycystic Ovarian Syndrome Undergoing In Vitro Fertilization

“…Moreover, metformin treatment does not lower the risk of developing gestational diabetes in high-risk women. 38 Because of the physiological role of metformin in anticell growth and proapoptosis, metformin treatment should be carefully considered during pregnancy.…”

Metformin for Preventing Type 2 Diabetes Mellitus in Women with a Previous Diagnosis of Gestational Diabetes: A Narrative Review

“…Ambiguity around screening guidelines 49,57,58 Health care system level Lack of care coordination when transitioning from secondary care to primary care in postpartum period 30,49,59 of serum androgen concentrations, Vanky and colleagues found, as a secondary outcome, metformin to be safe during pregnancy, but with no difference in the incidence of GDM between the intervention and control groups, as well as no difference in the primary outcome. 82 This was confirmed by more recent and larger RCTs of women with PCOS 83 and obesity 84 in pregnancy, a Cochrane review, 85 and a recent systematic review and meta-analysis, 81 all of which reported no preventive effect of metformin use during pregnancy on the incidence of GDM, albeit that this was not the primary outcome in the RCTs. More high-quality studies are required to examine the preventive effect of metformin use during pregnancy, particularly given the pharmacokinetic and physiological changes caused by pregnancy, 86,87 including an increase in insulin resistance in second and third trimesters.…”

“…79,80 Metformin has been examined for efficacy in the prevention of GDM in high-risk pregnant women (e.g., those with obesity, insulin resistance, and polycystic ovarian syndrome [PCOS]). 81 In a small pilot RCT (n ¼ 40) in women with PCOS taking metformin before pregnancy with a primary outcome 37 Experiencing emotional distress and feeling overwhelmed 37,57 Demands of baby's schedule 37 Perception of good personal health 37 Fear of receiving bad news at follow-up appointments 37 Dissatisfaction with care/poor experiences with medical care 37 Logistics of accessing health care 37…”

Therapeutic Potentials of Low-Dose Tacrolimus for Aberrant Endometrial Features in Polycystic Ovary Syndrome

“…Metformin may improve the menstrual cycle within 1-3 months; nonetheless, multiple reports from systemic reviews and randomized clinical trials indicate that metformin may not improve implantation and/or live birth rates or reduce miscarriage in women with PCOS [98][99][100]. More importantly, the use of metformin during pregnancy did not reduce maternal weight gain or avert gestational diabetes mellitus when initiated during pregnancy in at-risk women [101,102], nor did it reduce the relatively high obstetrical risk associated with increased rates of cesarean sections and the delivery of babies that were large for their gestational age and macrosomic babies (i.e., >4 or 4.5 kg at birth) [101][102][103].…”