Glucagon-Like Peptide-1 Receptor Agonists and Risk of Adverse Maternal Pregnancy Outcomes

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OBJECTIVE: To assess associations between pregestational and early-gestational exposure to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and maternal pregnancy complications. DATA SOURCES: A comprehensive search across the PubMed and EMBASE databases was conducted from inception to November 2025. METHODS OF STUDY SELECTION: Eligibility criteria for inclusion were 1) exposure to GLP-1 RAs before or during gestation; 2) cohort, case-control, or randomized controlled trial (RCT) study reporting quantitative data on maternal obstetric outcomes; and 3) study population greater than 10. Two reviewers independently abstracted study data and assessed quality and risk of bias using the Newcastle-Ottawa Quality Assessment Scale for observational studies and the Risk of Bias for Randomized Crossover Trials tool for RCTs. Odds ratios (ORs) were pooled using random effects with the Knapp-Hartung adjustment to reduce chance of false-positives and the restricted maximum likelihood estimator for heterogeneity testing. TABULATION, INTEGRATION, AND RESULTS: Eight studies totaling 186,598 pregnancies (47,159 exposed) were included. No statistically significant differences were seen for gestational diabetes (OR 0.99, 95% CI, 0.61-1.61), preterm birth (OR 1.01, 95% CI, 0.76-1.33), preeclampsia (OR 1.05, 95% CI, 0.60-1.84), or hypertensive disorder of pregnancy (OR 0.79, 95% CI, 0.34-1.83), although results from leave-one-out sensitivity testing suggest that GLP-1 RA exposure may have a protective effect against developing gestational diabetes (OR 0.81, 95% CI, 0.67-0.98). Newcastle-Ottawa Quality Assessment Scale results demonstrated variability in study quality and high heterogeneity attributable to differences in exposure and outcome definitions, cohort selection, and control for confounders. CONCLUSION: Use of a GLP-1 RA in the peri-fertilization period was not associated with change in odds of maternal pregnancy complications. Exploratory sensitivity results suggest that peri-fertilization exposure may lower odds of gestational diabetes. Further research is necessary to explore these hypotheses-generating results.

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