Gestational Weight Gain and Pregnancy Outcomes After GLP-1 Receptor Agonist Discontinuation

Importance Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are contraindicated in pregnancy. Discontinuation of GLP-1RAs proximal to pregnancy could affect gestational weight gain and pregnancy outcomes. Objective To compare gestational weight gain and pregnancy outcomes with and without exposure to GLP-1RAs before or during early pregnancy. Design, Setting, and Participants Retrospective cohort study of 149 790 singleton pregnancies delivered between June 1, 2016, and March 31, 2025, within a single academic health system. Exposure A GLP-1RA order between 3 years before and 90 days after conception, with propensity score matching of each exposed pregnancy to 3 unexposed pregnancies. Main Outcomes and Measures The primary outcome was gestational weight gain. Secondary outcomes were excess gestational weight gain, large and small for gestational age birth weight, birth weight percentile for gestational age and sex, birth length, preterm delivery, cesarean delivery, gestational diabetes, and hypertensive disorders of pregnancy. Results Among 149 790 pregnancies during the study period, 1792 (448 exposed and 1344 unexposed) were matched for the primary analysis. Exposed pregnancies had mean maternal age of 34.0 years (SD, 4.7 years) and prepregnancy body mass index of 36.1 (SD, 6.5; calculated as weight in kilograms divided by height in meters squared); 378 of 448 (84%) had obesity and 104 of 448 (23%) had preexisting diabetes; 136 (30%) were Hispanic, 49 (11%) were non-Hispanic Black, and 223 (50%) were non-Hispanic White; and 43 (10%) had public insurance. The GLP-1RA–exposed pregnancies had greater gestational weight gain (mean, 13.7 kg SD, 9.2) than propensity score–matched unexposed pregnancies (mean, 10.5 kg SD, 8.0), a difference of 3.3 kg (95% CI, 2.3-4.2; P lt; .001). The GLP-1RA–exposed group had a higher risk of excess gestational weight gain (65% vs 49%; risk ratio RR, 1.32; 95% CI, 1.19-1.47), greater mean birth weight percentile (58.4% vs 54.8%; difference, 3.6%; 95% CI, 0.2%-6.9%), and higher risk of preterm delivery (17% vs 13%; RR, 1.34; 95% CI, 1.06-1.69), gestational diabetes (20% vs 15%; RR, 1.30; 95% CI, 1.01-1.68), and hypertensive disorders of pregnancy (46% vs 36%; RR, 1.29; 95% CI, 1.12-1.49). There was no difference in birth length, risk of large or small for gestational age birth weight, or cesarean delivery. Conclusions and Relevance In a cohort composed primarily of women with obesity, GLP-1RA use with subsequent prepregnancy or early pregnancy discontinuation was associated with more gestational weight gain and a higher risk of preterm delivery, gestational diabetes, and hypertensive disorders of pregnancy.