Pregnancy outcomes following maternal GLP-1 receptor agonist exposure: a systematic review and meta-analysis

The objective of this systematic review and meta-analysis was to assess the risk of any and major congenital malformations and other adverse pregnancy outcomes following maternal exposure to glucagon-like peptide-1 receptor agonists during the periconceptional period and pregnancy. We conducted a systematic literature search of the PubMed, MEDLINE, Embase, Web of Science, and Reprotox electronic databases from inception through January 2026. Seven cohort studies encompassing over 40,000 exposed pregnancies were included. Maternal exposure to glucagon-like peptide-1 receptor agonists at any time during pregnancy was not associated with a statistically significant increase in any congenital malformations (OR, 1.11; 95% CI 0.82-1.51). First-trimester exposure did not significantly increase the risk of major congenital malformations (OR, 1.39; 95% CI 0.73-2.65). Furthermore, no significant risk increase was observed for stillbirth, spontaneous abortion, small for gestational age, or preterm birth. A significant association for urinary malformations was noted (OR, 1.24; 95% CI 1.05-1.47) based exclusively on unadjusted data. Maternal exposure to glucagon-like peptide-1 receptor agonists does not demonstrate a statistically significant association with major congenital malformations, stillbirth, spontaneous abortion, small for gestational age, or preterm birth. The urinary malformation signal relies on unadjusted estimates, likely reflecting residual confounding. These findings provide cautiously reassuring evidence regarding reproductive safety, though the certainty of evidence remains low.