Glucagon-like Peptide-1 Receptor Agonists among Pregnancies with Pregestational Diabetes and Its Relationship with Congenital Malformations

Background: Pregestational diabetes is a common complication seen in pregnancy, with significant increases seen in the use of glucagon-like peptide-1 receptor agonists (GLP-1 RA) for diabetes management in reproductive aged individuals. Objective: The objective of this study was to describe the perinatal outcomes and prevalence of congenital malformations associated with the use of GLP-1 RA in individuals with pregestational diabetes. Study Design: This study was a retrospective cohort study of patients with pregestational diabetes and pregnancies obtained from the Epic Cosmos database between May 1, 2022 and April 30, 2025. Demographics, perinatal outcomes, and prevalence of congenital malformations were compared by GLP-1 RA exposure in pregnancy. Categorical variables were compared with Chi-square and continuous variables were compared using student t-tests. No individual level data was available, so covariate adjustment was not performed. Results: The total sample population was 143,593 patients with pregestational diabetes, with 24.4% (n=35,083) of patients using a GLP-1 RA at some time point in pregnancy. Patients with GLP-1 RA usage were more likely to develop pre-eclampsia (13.1% vs. 11.9%, p<0.00001), have a cesarean delivery (44.4% vs. 38.9%, p<0.0001), have a first trimester pregnancy loss/termination (9.8% vs. 7.5%, p<0.00001), and a preterm delivery (23.1% vs. 20.8%, p<0.0001) when compared to patients without GLP-1 RA use. There was no statistically significant difference in the overall rate of any congenial malformation by GLP-1 RA use (3.3% in both groups, p=0.63). However, patients with GLP-1 RA usage were more likely to have fetuses with genital malformations (0.7% vs. 0.6%, p=0.02) and urinary malformations (0.5% vs. 0.4%, p=0.01) compared to patients without GLP-1 RA use. Conclusions: GLP-1 RA therapy in a large cohort of pregnant patients with pregestational diabetes was associated with an overall low rate of malformations but found an increase in genital and urinary malformations.