Safety of glucagon-like peptide-1 receptor agonists in pregnancy and lactation: a systematic review

Background The rapid adoption of glucagon-like peptide-1 receptor agonists (GLP-1RAs) among women of reproductive age necessitates assessment of their safety during pregnancy and lactation. Purpose This systematic review aims to identify knowledge gaps concerning the safety of GLP1-RAs during pregnancy and lactation. Methods We conducted a systematic review on Medline, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and CINAHL Plus for preclinical and clinical data on GLP1-RA exposure during pregnancy and/or lactation. The search was last updated in February 2026. Preclinical (animal) studies, human case reports, cohort studies, interventional studies, and product information from both the European Medicine Agency and the US Food and Drug Administration were included. We extracted data on maternal health outcomes, congenital malformations or morbidities in offspring, as well as data on transfer across the placenta or into breastmilk. Results We identified 5708 articles, of which 41 met the inclusion criteria. We included seven human cohorts, 12 case reports, four animal studies, two lactation studies, two preclinical placenta studies, and 14 product information sheets. The human cohorts reported on 38,261 exposed pregnancies (out of a total of 4,510,913 pregnancies) ranging in exposure from preconception to early pregnancy. The human cohorts did not identify any significant association between GLP-1RA exposure in early pregnancy and congenital abnormalities in the offspring. There was no data on exposure during late pregnancy. Animal studies showed visceral and skeletal malformations and reduced weight in the offspring, although these effects were commonly observed at dosages exceeding those used clinically in humans. The included studies showed that GLP-1RAs do not transfer across the placenta or into breastmilk in significant amounts in humans. Conclusion No consistent major safety concerns regarding GLP-1RAs during pregnancy and lactation were identified in human cohorts, although some animal studies reported adverse effects. Individual studies were small and inherently challenging to combine due to variations in inclusion criteria and confounder adjustments. Future study designs should consider these methodological challenges and focus on the balance between safety and efficacy of GLP-1RAs use during pregnancy and lactation.