Metformin Use in Pregnancy: Promises and Uncertainties

Robert S Lindsay,Mary R Loeken

doi:10.1097/01.ogx.0000530379.09409.2a

Abstract

(Abstracted from Diabetologia 2017;60:1612–1619) Metformin has been prescribed in pregnancy for more than 40 years, but it is since its increased use in polycystic ovarian syndrome treatment that exposure of the fetus to metformin in early pregnancy and its safety for both mother and child have been investigated more robustly. This review discusses the history, key trials, and controversies associated with metformin use in pregnancy.

Highlights

Metformin has been prescribed in pregnancy for over 40 years; for much of this time, use has been limited both in numbers and geographically, and the evidence base has been confined to observational studies
It was as metformin use became more popular in polycystic ovarian syndrome (PCOS) that a more robust literature developed, investigating exposure of the fetus to metformin in early pregnancy and, safety of its use
This study suggested that metformin may have superior outcomes to the only other oral glucose-lowering agent used in pregnancy, glibenclamide, only few head-tohead studies were used in the analysis [15]

Summary

Early use

The initial development and use of metformin (outside of pregnancy) are reviewed elsewhere in this issue of Diabetologia [1]. The safety concerns related to phenformin use resulted in the withdrawal of metformin in many, not all, countries [3] These early concerns are charted in influential reports of the Aberdeen International Colloquia on Carbohydrate Metabolism in Pregnancy and the Newborn. In South Africa and other countries, where metformin was routinely used to treat type 2 diabetes, exposure inevitably began to occur in early pregnancy leading to the separate analysis of safety in early pregnancy, regarding miscarriage and congenital anomaly. It was as metformin use became more popular in polycystic ovarian syndrome (PCOS) that a more robust literature developed, investigating exposure of the fetus to metformin in early pregnancy and, safety of its use

Safety and efficacy of metformin during pregnancy

RagC GTPase mTOR

International use of metformin

Findings

Conclusions