Periconceptional Use of GLP-1 Receptor Agonists and the Risk of Major Congenital Malformations: A Systematic Review and Meta-analysis.

Authors

Xiangxian Liu, Beijia Xiong, Rui Yang, Haining Wang, Ye Liu

Published in

Endocrine connections. Jul 07, 2026. Epub Jul 07, 2026.

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for metabolic diseases, but their reproductive safety remains controversial. We assessed the impact of periconceptional GLP-1RAs exposure on birth outcomes to inform their use in reproductive-aged women. PubMed, Embase, Web of Science (through December 2025) were searched for RCTs/cohorts reporting offspring or pregnancy outcomes in women exposed to GLP-1RAs within three months before conception or during pregnancy. The primary outcome was major congenital malformations (MCMs), compared between neonates with or without maternal GLP-1RAs exposure. Secondary outcomes were spontaneous abortion, stillbirth, preterm birth, large for gestational age (LGA), and small for gestational age (SGA). One prospective and five retrospective studies involving 286599 women (43577 exposed, 243022 unexposed to GLP-1RAs) were included. Meta-analysis showed no significant difference in MCMs risk among the GLP-1RAs exposure group, compared to the non-exposure group (relative risk [RR] 1.02, 95% CI 0.96-1.08). Risks of preterm birth (RR 1.09, 95% CI 0.80-1.49), LGA (RR 2.31, 95% CI 0.56-9.44), SGA (RR 0.71, 95% CI 0.39-1.27), and stillbirth (RR 1.16, 95% CI 0.24-5.69) weren't significantly elevated. The incidence of spontaneous abortion was comparable between the two groups in one study. Evidence suggests that periconceptional GLP-1RAs exposure in women isn't associated with increased risk of MCMs or other adverse birth outcomes. But given the observational design and limited exposed pregnancies, these findings should not be interpreted as proof of safety. Large prospective cohorts and RCTs are needed to confirm the safety of GLP-1RAs usage before pregnancy.

PMID:
42447044
Bibliographic data and abstract were imported from PubMed on 15 Jul 2026.

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