Semaglutide exposure in early pregnancy shows no major fetal anomalies in 16-patient case series

The escalating use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) like semaglutide has significantly improved blood sugar control and body weight, often enhancing fertility. This has led to an increasing number of individuals inadvertently becoming pregnant while on these medications. Current data on the safety and outcomes of GLP-1 RA exposure during the crucial first trimester of pregnancy, particularly regarding major congenital malformations and maternal metabolic health, remains scarce. This gap in knowledge creates a clinical dilemma for managing obesity and diabetes in early pregnancy when GLP-1 RAs are discontinued, necessitating more real-world evidence.

This case series retrospectively reviewed 16 patients receiving obstetric care at a tertiary perinatal center. All participants had inadvertent exposure to subcutaneous semaglutide (dose not specified) from up to 2 months preconception and continued administration during a portion of the first trimester. All patients had spontaneous, unplanned singleton pregnancies and were classified as overweight or obese. Researchers reviewed electronic medical records to assess fetal, obstetrical, maternal, and neonatal outcomes, including the incidence of major malformations, maternal glucose control, and gestational weight gain. No specific control arm was utilized, as this was an observational case series, focusing on real-world outcomes.

Among the 16 patients inadvertently exposed to semaglutide in the first trimester, no major fetal anomalies were identified. Despite the continuation of semaglutide into early pregnancy, no individual experienced weight loss during pregnancy. Following the discontinuation of semaglutide, most patients required a combination of both metformin and insulin to achieve adequate diabetes control, highlighting the challenge of managing glycemic control post-cessation. The study observed one instance of iatrogenic preterm birth at 35 weeks due to preeclampsia. > The overall rate of preeclampsia within this cohort was 18.8%, which is notable given the patient population's baseline risk factors. Furthermore, the rate of excessive gestational weight gain (EGWG) was 37.5%, which was considered lower than expected for a cohort with a high baseline prevalence of obesity, suggesting a potential residual benefit or unique metabolic profile in these patients. All pregnancies were singleton, and conception was spontaneous and unplanned.