OBJECTIVE: To examine gestational weight gain and pregnancy outcomes (eg, gestational diabetes, preterm birth) among individuals with overweight or obesity who had semaglutide exposure before and during pregnancy.
METHODS: This is a retrospective cohort study using a national-level dataset that links electronic medical record and pharmacy dispensing data (Truveta). Women with prepregnancy overweight or obesity who delivered between January 2022 and January 2026 were classified into three groups based on semaglutide use: 1) pregnancy-exposed users (before and into pregnancy), 2) former users (before pregnancy only), and 3) nonusers. Preterm birth was defined as delivery between 24 and 37 completed weeks of gestation. Gestational diabetes, pregnancy-related hypertension, intrauterine growth restriction, excessive fetal growth, and cesarean delivery were identified using International Classification of Diseases, Tenth Revision codes. To reduce confounding, 1:1 propensity score matching was performed based on maternal age, race and ethnicity, prepregnancy body mass index (BMI), prepregnancy diabetes, and prepregnancy hypertension. In the matched cohorts, linear and logistic regression models were used with additional adjustment for residual confounding.
RESULTS: Pregnancy-exposed users (n=429) had a mean age of 32.7±4.9 years at delivery, a mean prepregnancy BMI of 36.9±6.8, and a median total exposure time in pregnancy of 44 days. Compared with nonusers (n=2,203), pregnancy-exposed users had higher risk of excessive gestational weight gain (adjusted odds ratio [aOR]=2.88, 95% CI, 2.04-4.05), gestational diabetes (aOR=1.59, 95% CI, 1.03-2.44), excessive fetal growth (aOR=1.78, 95% CI, 1.03-3.08), and cesarean delivery (aOR=3.35, 95% CI, 2.15-5.22). Similarly, former users (n=801) also had higher risks of excessive gestational weight gain (aOR=1.98, 95% CI, 1.56-2.51), gestational diabetes (aOR=1.43, 95% CI, 1.05-1.93), excessive fetal growth (aOR=1.54, 95% CI, 1.01-2.36), and cesarean delivery (aOR=3.92, 95% CI, 2.81-5.47) compared with nonusers. No statistically significant differences in gestational weight gain or pregnancy outcomes were observed between pregnancy-exposed users and former users.
CONCLUSION: Semaglutide exposure prior to and during pregnancy was associated with higher risks of adverse pregnancy outcomes compared with no semaglutide use. There were no differences when comparing those who discontinued prior to or during pregnancy, suggesting that the elevated risks are more likely attributable to rebound effects after treatment discontinuation rather than to intrauterine exposure itself.
GLP-1 Therapies