Semaglutide exposure before/during pregnancy increases risks for excessive weight gain, gestational diabetes, C-sections.
Background
Managing overweight and obesity during pregnancy is crucial, as both are linked to adverse maternal and fetal outcomes, including gestational diabetes (GDM) and excessive gestational weight gain (GWG). Current interventions often fall short, highlighting a need for effective strategies. Semaglutide, a potent GLP-1R agonist, is highly effective for weight loss in non-pregnant individuals. However, its safety and impact on pregnancy outcomes when exposed before or during gestation remain a significant clinical concern, as weight loss medications are generally contraindicated in pregnancy.
Study Design
This retrospective cohort study utilized a national-level dataset (Truveta) linking electronic medical records and pharmacy dispensing data. Researchers identified women with prepregnancy overweight or obesity who delivered between January 2022 and January 2026. Participants were categorized into three groups: pregnancy-exposed users (semaglutide before and into pregnancy), former users (semaglutide before pregnancy only), and nonusers. To control for confounding, 1:1 propensity score matching was performed based on maternal age, race/ethnicity, prepregnancy BMI, prepregnancy diabetes, and hypertension. Outcomes like gestational diabetes, pregnancy-related hypertension, and cesarean delivery were identified using International Classification of Diseases, Tenth Revision codes (ICD-10 codes).
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 demonstrated significantly higher risks across several adverse outcomes. They had an adjusted odds ratio (aOR) of 2.88 (95% CI, 2.04-4.05) for excessive gestational weight gain, an aOR of 1.59 (95% CI, 1.03-2.44) for gestational diabetes, and an aOR of 1.78 (95% CI, 1.03-3.08) for excessive fetal growth. Former users (n=801) also showed elevated risks, with an aOR of 1.98 (95% CI, 1.56-2.51) for excessive gestational weight gain, an aOR of 1.43 (95% CI, 1.05-1.93) for gestational diabetes, and an aOR of 1.54 (95% CI, 1.01-2.36) for excessive fetal growth. The most pronounced risk was for cesarean delivery:
Pregnancy-exposed users faced a 3.35-fold higher adjusted odds of cesarean delivery (95% CI, 2.15-5.22) compared to nonusers.
Key Findings
- Pregnancy-exposed semaglutide users had 2.88-fold higher odds of excessive gestational weight gain (95% CI, 2.04-4.05).
- Pregnancy-exposed users showed 1.59-fold higher odds of gestational diabetes (95% CI, 1.03-2.44).
- Cesarean delivery odds were 3.35-fold higher in pregnancy-exposed users (95% CI, 2.15-5.22).
- Former semaglutide users also had increased risks for excessive gestational weight gain (aOR=1.98) and gestational diabetes (aOR=1.43).
- Excessive fetal growth was 1.78-fold more likely in pregnancy-exposed users (95% CI, 1.03-3.08).
Why It Matters
This study provides critical real-world data underscoring the potential risks associated with semaglutide exposure before and during pregnancy. For individuals using GLP-1R agonists for weight management, these findings strongly reinforce the importance of discontinuation prior to conception and meticulous pregnancy planning. Clinicians should counsel patients about these elevated risks, particularly for excessive gestational weight gain, gestational diabetes, and cesarean delivery, even if exposure is limited to the periconceptional period. This research highlights the need for strict adherence to current guidelines recommending against GLP-1R agonist use during pregnancy.
semaglutide
pregnancy
gestational-weight-gain
gestational-diabetes
cesarean-delivery
obesity