First-trimester GLP-1 exposure not tied to higher risk of adverse pregnancy outcomes

Clinical Takeaway: Unintentional early pregnancy exposure to GLP-1 receptor agonists may be less concerning than previously feared. Although these data don't establish safety, they may help inform counseling when pregnancy occurs before a GLP-1 can be discontinued.

GLP-1 receptor agonist use has increased rapidly among women of reproductive age for both type 2 diabetes and obesity. Yet clinicians have had little human data to guide counseling when pregnancy occurs during treatment.

In this large US study, investigators examined pregnancy outcomes among women who'd recently used a GLP-1 receptor agonist and either continued treatment into the first trimester or didn't continue treatment after the last menstrual period.

The study found no definitive increase in the risk of nonlive birth, major congenital malformations, small-for-gestational-age birth, or large-for-gestational-age birth among women who continued GLP-1 therapy into early pregnancy compared with those who didn't.

Among more than 3,500 pregnancies, the risk of nonlive birth was similar between groups. Rates of major congenital malformations and abnormal fetal growth also didn't differ significantly, although the confidence intervals were wide enough that a clinically important increase or decrease in risk couldn't be excluded.

The findings are clinically important because current evidence on GLP-1 exposure during pregnancy remains limited and many pregnancies are unplanned. As use of semaglutide, tirzepatide, and related agents continues to expand, clinicians are increasingly faced with questions about inadvertent first-trimester exposure.

The authors emphasized that the results shouldn't be interpreted as proof of safety. However, the study provides some of the strongest human data to date on early-pregnancy GLP-1 exposure and may help inform risk discussions when treatment is continued inadvertently.

Source: Brown JP, et al. 2026 June 9. Ann Intern Med. Continuing Glucagon-Like Peptide-1 Receptor Agonists Into the First Trimester of Pregnancy and Pregnancy Outcomes: A Target Trial Emulation Study Using Claims Information