Maternal use of such drugs during pregnancy (compared with insulin) was not associated with congenital malformations.

Because of limited data on the effects of noninsulin diabetes medications on fetal development, the American Diabetes Association recommends insulin for managing type 2 diabetes in pregnancy (Diabetes Care 2023; 46: Suppl 1: S254-S266). However, both intentional use of metformin and unintentional exposure to other second-line drugs during pregnancy have increased. In this observational, population-based study, researchers assessed noninsulin diabetes medication use and risk for major congenital malformations among 3.5 million pregnancies in six countries from 2009 to 2021.

Of 52,000 pregnant women with type 2 diabetes, 15,000 used diabetes medications between 90 days before pregnancy and the end of the first trimester. The prevalence of major congenital malformations was 3.8% in all infants; 5.3% in those whose mothers had type 2 diabetes, 5.3% in those exposed to metformin, 7.8% in those exposed to insulin and 6.1% to 9.7% in those exposed to all other noninsulin diabetes drugs. Adjusted risks for major congenital malformations and cardiac malformations were not significantly different between infants exposed to insulin and those exposed to each of the noninsulin medications.

Comment: These results provide some reassurance that infants exposed to noninsulin diabetes medications are not at significant excess risk for congenital malformations, but residual confounding is possible. For now, insulin remains the first-line standard of care, although recent randomised trials have been exploring whether add-on metformin therapy confers any additional benefit (NEJM JW Gen Med Feb 1 2024 and JAMA 2023; 330: 1547-1556 and JAMA 2023; 330: 2182-2190).

Paul S. Mueller, MD, MPH, FACP, Regional Vice President – Southwest Wisconsin, Mayo Clinic Health System, La Crosse; Professor of Medicine and Biomedical Ethics, Mayo Clinic College of Medicine and Science, Rochester, USA., Regional Vice President – Southwest Wisconsin, Mayo Clinic Health System, La Crosse; Professor of Medicine and Biomedical Ethics, Mayo Clinic College of Medicine and Science, Rochester, USA.

Cesta CE, et al. Safety of GLP-1 receptor agonists and other second-line antidiabetics in early pregnancy. JAMA Intern Med 2024;184: 144-152.

This summary is taken from the following Journal Watch titles: General Medicine, Ambulatory Medicine, Women’s Health.