Glucagon-like peptide-1 receptor agonist use in pregnancy: a review

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are peptide analogues that are used to treat type 2 diabetes mellitus (T2DM) and obesity. The first medication in this class, Exenatide, was approved in 2005, and these medications, specifically Semaglutide, have become more popular in recent years due to their pronounced effects on glycemic control, weight reduction, and cardiovascular health. Due to successful weight loss from these medications, many women previously diagnosed with oligomenorrhea and unable to conceive have experienced unplanned pregnancies while taking the medications. However, there is currently little data for clinicians to use in counseling patients in cases of accidental periconceptional exposure. In some studies examining small animals exposed to GLP-1RAs in pregnancy, there has been evidence of adverse outcomes in the offspring, including decreased fetal growth, skeletal and visceral anomalies, and embryonic death. Although there are no prospective studies in humans, case reports, cohort studies, and population-based studies have not shown a pattern of congenital anomalies in infants. A recent large, observational, population-based cohort study examined 938 pregnancies affected by T2DM and compared outcomes from periconceptional exposure to GLP-1RAs and insulin. The authors concluded there was not a significantly increased risk of major congenital malformations in patients taking GLP-1RAs, although there was no information on maternal glycemic control or diabetic fetopathy. As diabetic embryopathy is directly related to the degree of maternal hyperglycemia and not the diagnosis of diabetes itself, it is not possible to make this conclusion without this information. Furthermore, there is little evidence available regarding fetal growth restriction, embryonic or fetal death, or other potential complications. At this time, patients should be counseled there is not enough evidence to predict any adverse effects, or the lack thereof, of periconceptional exposure of GLP-1RAs during pregnancy. We recommend that all patients use contraception to prevent unintended pregnancy while taking GLP-1RAs.