Endocrinology AdvisorSemaglutide Exposure in Pregnancy Related to Adverse Outcomes

ℹ️ Observational Association Only Evidence

Researchers used linked electronic medical record and pharmacy data from 30 US health systems to examine pregnancy outcomes among patients with overweight or obesity who used semaglutide before or during pregnancy. The analysis included 1,230 semaglutide users and 2,203 nonusers. Both pregnancy-exposed and former users had higher risks for several outcomes, suggesting that metabolic changes after discontinuation or underlying clinical characteristics may contribute more than direct in utero exposure.

Clinical Considerations

• Pregnancy-exposed users gained 5.12 kg more during gestation than matched nonusers.
• Exposure was associated with excessive gestational weight gain (aOR, 2.88) and gestational diabetes (aOR, 1.59).
• Excessive fetal growth was more frequent among exposed users, with an adjusted OR of 1.78.
• Cesarean delivery showed the largest association among pregnancy-exposed users: aOR, 3.35; 95% CI, 2.15–5.22.
• Former users showed similar outcome patterns, and differences between former and pregnancy-exposed users were not statistically significant.
• Exposure timing may have been misclassified, and the study could not assess congenital anomalies or fully control for diabetes, pregnancy intention, lifestyle, and other factors.

Practice Applications

• Review semaglutide use and discontinuation timing during preconception counseling.
• Recognize that post-discontinuation weight and metabolic changes may complicate pregnancy risk assessment.
• Monitor gestational weight gain and glycemic status in patients with recent GLP-1 therapy.
• Avoid attributing the observed outcomes directly to fetal semaglutide exposure based on this study.
• Interpret the findings alongside underlying obesity, diabetes, prior cesarean delivery, and medication indication.