SUN-115 - Addressing the Evidence Gap: A Case Series of Glucagon-Like Peptide-1 Receptor Agonist Use in Prepregnancy and Early Pregnancy

Background: Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use has reshaped the management of obesity and metabolic disease for many. However, data informing their safety and efficacy in prepregnancy and pregnancy remains limited. Current Food and Drug Administration (FDA) labeling and national society guidelines recommend against GLP-1 RA use in the immediate prepregnancy and pregnancy periods, citing teratogenic effects observed in animal models, and potential adverse obstetric outcomes. However, human data informing these associations remains limited and conflicting. Nevertheless, guidelines recommend discontinuing GLP-1 RAs 1 to 2 months prior to pregnancy. These recommendations are not distinguished by indication. In sum, a paucity of reproductive-specific data on GLP-1 RA use continues to constrain evidence-based guideline updates.
Case Presentations: We report 3 cases of women between the ages of 30 to 40 with singleton pregnancies exposed to GLP-1 RAs prior to pregnancy through early gestation (up to 8 weeks’). All patients were managed at a single academic center with longitudinal follow-up over 2 years for mother and infant. Indications for therapy included glycemic control and weight management in the setting of type 2 diabetes mellitus. During pregnancy, the patients were treated with insulin and/or metformin for glycemic control. Two patients were exposed to semaglutide and one to tirzepatide in the prepregnancy and early gestation periods. Among patients exposed to semaglutide, one underwent a scheduled cesarean delivery without adverse pregnancy outcomes (APO); the neonate’s weight was appropriate for gestational age (AGA) with no congenital abnormalities noted on initial or subsequent follow-up. The second semaglutide-exposed pregnancy was induced at 37 weeks gestation due to a small for gestational age ( < 2nd percentile) neonate. This fetus had been diagnosed with trisomy 18 earlier in pregnancy, with neonatal demise occurring shortly after birth. The patient exposed to tirzepatide underwent cesarean delivery following arrest of descent after a trial of labor. The pregnancy was complicated by preeclampsia without severe features diagnosed during delivery. The neonate was AGA with no abnormalities on initial or follow-up evaluations.

Discussion: While there is no consistent pattern of adverse obstetric or neonatal outcomes following GLP-1 RA exposure prior to and during early gestation in these 3 patients, complications of fetal growth restriction and preeclampsia were observed, as well as cesarean delivery in all patients. The occurrence of fetal growth restriction in one pregnancy is likely from the known trisomy diagnosis. However, the role of the GLP-1 RA exposure is unclear. Prospective studies are needed to further evaluate reproductive safety of this novel medication class.

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