Preprints.org · Oct 16, 2026

Continuing Semaglutide into the First Trimester of Pregnancy Is Not Associated with Maternal or Newborn Complications in Routine Care

By Matson R, Venkatakrishnan A, Varma G et al.

Semaglutide is recommended to be stopped 2 months before planned pregnancy, but maternal-fetal outcomes following continued exposure remain incompletely characterized. We examined 363,778 pregnancies between January 2018 and March 2025 in de-identified electronic health records from a large U.S. federated data network. Of these, 572 pregnancies had a semaglutide prescription within 90 days before the last menstrual period (LMP), after excluding pregnancies involving other glucagon-like peptide-1 (GLP-1) therapies, type 1 diabetes, or multiple gestation. Semaglutide was prescribed in 246 of the 572 pregnancies (43.0%) during the first trimester (0 to 13 weeks), in 54 of the 360 pregnancies (15.0%) that reached the second trimester (14 to 27 weeks), and in 45 of the 345 pregnancies (13.0%) that reached the third trimester (28 weeks to delivery). Of the 246 pregnancies with a semaglutide prescription order in the first trimester, large language model (LLM)-curated review of the clinical notes confirmed use in 225 women (91.5%) and use once the pregnancy was known in 186 women (75.6%). Further, among pregnancies with a recorded semaglutide dose, the most common highest dose increased from 0.25–0.5 mg during the 3 months before pregnancy (47.5%) to 1–1.7 mg in the first trimester (46.2%), while the proportion prescribed 2–2.4 mg increased from 18.8% to 23.4%. Among 572 semaglutide users and 101,159 similar pregnancies without GLP-1 use exactly matched on age group, LMP year, type 2 diabetes, obesity, and PCOS, similar rates of pregnancies reached the second trimester (62.9% vs 66.7%; P=0.08), third trimester (60.3% vs 64.1%; P=0.08), and delivery (61.4% vs 65.5%; P=0.06). Among the 572 semaglutide users, 146 women prescribed semaglutide during the first trimester gave birth (“semaglutide-continued”) and 185 women had no semaglutide prescription during pregnancy gave birth (“semaglutide-discontinued”). Comparing these groups did not show any significant differences (q≥0.05) in the risk of preeclampsia/eclampsia, gestational hypertension, new high blood pressure from 20 weeks, gestational diabetes, gallbladder disease, cesarean delivery, or postpartum hemorrhage. Among newborns to the semaglutide-continued versus newborns to the semaglutide-discontinued groups, rates of preterm birth, stillbirth or neonatal death also did not differ. Furthermore, among infants with a recorded 5-minute Apgar score (Appearance, Pulse, Grimace, Activity, and Respiration), the mean scores (8.5 versus 8.6) and the rates of scores less than 7 were both indistinguishable between the semaglutide-continued and the semaglutide-discontinued groups. In a secondary comparison of 858 semaglutide-exposed and 3,995 metformin-exposed pregnancies, defined by a prescription from 90 days before the LMP through the first trimester, pregnancy loss or stillbirth did not differ significantly. Among pregnancies that resulted in a delivery, maternal complications, cesarean delivery, preterm birth, and newborn outcomes, including the 5-minute Apgar score, did not differ significantly between the semaglutide-exposed and metformin-exposed groups. Overall, semaglutide prescribing during pregnancy was not associated with significant differences in maternal or newborn outcomes studied in this routine care setting. These observations motivate the need for larger retrospective and prospective studies to rigorously establish the safety of semaglutide exposure during pregnancies with underlying cardiometabolic burden.

doi.org/10.20944/preprints202610.1639.v1Open accessPopulations