Metformin Therapy During Pregnancy

Abstract

Type 2 diabetes and gestational diabetes mellitus (GDM) are closely related disorders characterized by increased insulin resistance. Metformin, a biguanide compound, exerts its clinical effect by both reducing hepatic glucose output and by increasing insulin sensitivity. This results in a decreased glucose level without an associated high risk of either hypoglycemia or weight gain. These characteristics have established metformin as an ideal first-line treatment for people with type 2 diabetes and, hypothetically, a particularly attractive drug for use in pregnancy. However, metformin is known to cross the placenta (1,2), and its use in pregnancy has been limited by concerns regarding potential adverse effects on both the mother and the fetus. Historically, some of the earliest reports of the use of metformin during pregnancy have come from South Africa, where it has been used since the late 1970s for women with both type 2 diabetes and GDM (3–6). While perinatal mortality for these women was still higher than that seen in the general obstetric population, it was nonetheless lower than in women who had gone untreated and similar to those who were changed to insulin. No “headline” adverse events or side effects were reported. Confidence regarding the use of metformin in pregnancy has been reinforced by the results of several observational studies and randomized trials over the past decade. Two meta-analyses of observational studies—one of women using metformin and/or sulphonylureas and one of women using metformin alone during the first trimester—did not show an increase in congenital malformations or neonatal deaths (7,8). While increased perinatal mortality and pre-eclampsia was noted in …