OBJECTIVE To investigate the safety of glucagon-like peptide-1 receptor agonist(GLP-1RA) in pregnant patients and provide evidence-based support for pharmaceutical services and clinical treatment for patients.
METHODS PubMed, Embase, The Cochrane Library, CNKI and Wanfang Database were systematically searched to collect studies of GLP-1RA exposure in pregnant women from inception to June 9, 2025. Two reviewers independently screened literature, extracted data, and assessed the risk of bias in included studies. Meta-analysis was then performed by using Review Manager 5.4 software.
RESULTS A total of 14 studies were included, comprising 3 cohort studies and 11 case series/case report studies. The results of the meta-analysis of the 3 cohort studies showed that, compared with pregnant women not exposed to GLP-1RA, exposure to GLP-1RA during pregnancy did not increase the risk of major congenital malformations in newborns(RR=0.99, 95%CI 0.79 to 1.24, P=0.90), preterm birth(RR=0.63, 95%CI 0.41 to 0.97 P=0.03), or small for gestational age(RR=0.68, 95%CI 0.39 to 1.19 P=0.18). However, it might reduce the live birth rate(RR=0.90, 95%CI 0.83 to 0.97 P=0.008). Results from 11 case series/reports showed that 24 pregnancies were exposed to GLP-1RA, including 15 exposures to semaglutide, 3 exposures to dulaglutide, and 3 exposures to liraglutide, and 3 pregnancies exposed to exenatide. Among these, only 1 fetus had severe cardiac abnormalities, and 1 male infant exhibited mild bilateral renal pyelectasis, while the remaining 22 were healthy newborns.
CONCLUSION Current limited evidence suggests that while exposure to GLP-1RA during pregnancy may reduce live birth rate, it does not increase incidence of major congenital malformations, preterm birth, or small-for-gestational-age newborns. Disease and different GLP-1RA may be confounding factors, and further high-quality data are needed for validation.
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