This systematic review and meta-analysis examined whether periconceptional or first-trimester exposure to GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide, tirzepatide, exenatide, lixisenatide, albiglutide) was associated with hypertensive disorders of pregnancy (HDP), pooling data from 3 retrospective US cohort studies (2014–2025) covering 10,880 pregnancies (4,942 exposed, 5,938 unexposed).
Pooled analysis showed no statistically significant association between GLP-1 RA exposure and HDP risk (OR 0.91, 95% CI 0.57–1.47); 2 of 3 studies found lower HDP risk in exposed women (ORs 0.56 and 0.84), while 1 found higher risk, with high heterogeneity across studies.
- Only 3 retrospective cohort studies were available, all from the US, limiting generalizability. - Two studies relied on ICD-10 codes for HDP diagnosis, which may underreport or misclassify cases. - Abrupt GLP-1 RA discontinuation before conception may cause gestational weight rebound, confounding the HDP risk estimate.
Current evidence does not support a significant protective or harmful effect of periconceptional or first-trimester GLP-1 RA use on HDP risk; clinicians should counsel patients that data are insufficient to guide decisions, and large prospective studies are needed before changing practice.
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