Neonatal and obstetric outcomes following periconceptional exposure to glucagon-like peptide-1 receptor agonists: a systematic review and meta-analysis

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OBJECTIVE: To evaluate the association between periconceptional exposure to glucagon-like peptide-1 receptor agonists and fetal, pregnancy-related, obstetric, and delivery outcomes. DATA SOURCES: PubMed, Embase, and Web of Science were searched from database inception through November 2025 to identify relevant studies. STUDY ELIGIBILITY CRITERIA: Cohort and observational studies comparing human pregnancies with periconceptional glucagon-like peptide-1 receptor agonist exposure to unexposed comparator groups were included. Case reports and case series were also included for narrative synthesis. Studies involving nonhuman animals were excluded from the primary meta-analysis but referenced in the background synthesis. STUDY APPRAISAL AND SYNTHESIS METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Random-effects meta-analyses were performed using odds ratios or mean differences with 95% confidence intervals. Heterogeneity was assessed using the I-squared statistic. Sensitivity analyses were conducted using comparator-specific control groups to account for maternal disease. RESULTS: Twenty-two studies, comprising 49,395 human pregnancies with periconceptional glucagon-like peptide-1 receptor agonist exposure, were included. Meta-analysis of 10 cohort and observational studies showed no statistically significant association between exposure and major congenital malformations, cardiac malformations, gestational age and weight, preterm delivery, live birth, spontaneous pregnancy loss, hypertensive disorders of pregnancy, or cesarean delivery. A small but statistically significant association with renal malformations was detected (odds ratio, 1.23; 95% confidence interval, 1.09-1.39); however, this was largely driven by a single large cohort with substantial baseline imbalances. Heterogeneity was moderate to high for several outcomes. Narrative synthesis of case reports and series identified no consistent pattern of adverse outcomes. CONCLUSION: Current human evidence does not demonstrate a consistent association between periconceptional glucagon-like peptide-1 receptor agonist exposure and major adverse fetal, pregnancy, obstetric, or labor outcomes. The observed risk for renal malformations should be interpreted with caution as it likely reflects residual confounding by maternal disease severity. These findings provide cautious reassurance following inadvertent exposure but do not support routine use during pregnancy, highlighting the need for robust studies with long-term follow-up.

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