Gestational Weight Gain and Hypertensive Disorders of Pregnancy With Prepregnancy and Early Pregnancy Glucagon-Like Peptide-1 Receptor Agonist Exposure

Abstract

Objective: To evaluate the associations among peripregnancy glucagon-like peptide-1 receptor agonist (GLP-1RA) exposure with hypertensive disorders of pregnancy (HDP) and gestational weight gain.

Methods: We conducted a retrospective cohort study that included patients who delivered between 2014 and 2024 and had GLP-1RA exposure up to 1 year before pregnancy. Participants were identified through electronic medical record query with manual medical record abstraction to confirm exposure stop dates. Exposure to GLP-1RAs was classified by indication: pregestational diabetes mellitus or weight management. Unexposed control groups for each indication cohort were identified from an existing institutional data repository from 2021 to 2022. Demographic and clinical characteristics and obstetric outcomes were compared. The two primary outcomes were gestational weight gain and HDP. Gestational weight gain was quantified as below, meeting, or exceeding recommended gestational weight gain. Crude odds ratios and adjusted odds ratios (aORs) were estimated using multivariable modeling. Regression analysis was stratified as GLP-1RA exposure prepregnancy only or during pregnancy.

Results: We included 243 patients who were exposed to GLP-1RA up to 1 year before pregnancy, with 65.4% having evidence of use during pregnancy. Overall, 103 (42.4%) patients used GLP-1RA for pregestational diabetes and 140 (57.6%) patients used it for weight management, compared with 175 unexposed patients in the pregestational diabetes control group and 200 unexposed patients in the weight-management control group (body mass index [BMI] 30-39.9: n=100; BMI 40 or higher: n=100). Exposure to GLP-1RAs was not associated with gestational weight gain in the pregestational diabetes cohort but was associated with decreased odds of gestational weight gain below recommendations (aOR 0.38, 95% CI, 0.18-0.80) in the weight-management cohort. Exposure to GLP-1RAs was associated with lower odds of HDP when compared with unexposed individuals with pregestational diabetes (aOR 0.52, 95% CI, 0.30-0.90) and with unexposed individuals who were undergoing weight management (aOR 0.51, 95% CI, 0.30-0.87). These associations were slightly more robust among patients exposed during pregnancy.

Conclusion: In individuals undergoing weight management, peripregnancy GLP-1RA exposure was associated with decreased risk of gestational weight gain below recommendations, which may reflect rebound weight gain after cessation. Peripregnancy GLP-1RA exposure was associated with lower odds of developing HDP for both the pregestational diabetes and weight-management cohorts. Additional studies are needed to guide GLP-1RA use in pregnancy and to better elucidate any risks of exposure.