Glucagon-Like Peptide-1 Receptor Agonists and Risk of Adverse Maternal Pregnancy Outcomes: A Systematic Review and...

To assess associations between pregestational and early-gestational exposure to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and maternal pregnancy complications.

A comprehensive search across the PubMed and EMBASE databases was conducted from inception to November 2025.

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.

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.

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.