Efficacy and safety of metformin during pregnancy in women with gestational diabetes mellitus or polycystic ovary syndrome: a systematic review

Metabolism. 2013 Nov;62(11):1522-34. doi: 10.1016/j.metabol.2013.06.006. Epub 2013 Jul 23.


Background: Metformin is an effective oral anti-hyperglycemic agent that is widely used to manage diabetes mellitus type 2 in the general population and more recently, in pregnancy. However, as metformin crosses the placenta, its use during pregnancy raises concerns regarding potential adverse effects on the mother and fetus.

Objective: (i) To provide background for the use of metformin during pregnancy through a narrative review and (ii) to critically appraise the published evidence on the efficacy and safety of using metformin during pregnancy through a systematic review.

Results: Metformin appears to be effective and safe for the treatment of gestational diabetes mellitus (GDM), particularly for overweight or obese women. However, patients with multiple risk factors for insulin resistance may not meet their treatment goals with metformin alone and may require supplementary insulin. Evidence suggests that there are potential advantages for the use of metformin over insulin in GDM with respect to maternal weight gain and neonatal outcomes. Furthermore, patients are more accepting of metformin than insulin. The use of metformin throughout pregnancy in women with polycystic ovary syndrome reduces the rates of early pregnancy loss and preterm labor and protects against fetal growth restriction. There have been no demonstrable teratogenic effects, intra-uterine deaths or developmental delays with the use of metformin.

Conclusions: The publications reviewed in this paper support the efficacy and safety of metformin during pregnancy with respect to immediate pregnancy outcomes. Because there are no guidelines for the continuous use of metformin in pregnancy, the duration of treatment is based on clinical judgment and experience on a case-by-case basis.

Keywords: FDA; FFA; Food and Drug Administration; Free Fatty Acid; GMD; Gestational Diabetes Mellitus; Gestational diabetes mellitus; MIG; Metformin; Metformin versus insulin for gestational diabetes; OGLA; Oral glucose lowering agents; PCOS; Polycystic ovary syndrome; Pregnancy; Systematic review; T2DM; Type 2 Diabetes Mellitus.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Clinical Trials as Topic
  • Diabetes, Gestational / drug therapy*
  • Female
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / adverse effects
  • Insulin / therapeutic use
  • Insulin Resistance
  • Metformin / adverse effects
  • Metformin / pharmacology
  • Metformin / therapeutic use*
  • Obesity / complications
  • Polycystic Ovary Syndrome / drug therapy*
  • Pregnancy
  • Pregnancy Complications
  • Pregnancy Outcome
  • Treatment Outcome


  • Hypoglycemic Agents
  • Insulin
  • Metformin