Safety of GLP-1 and dual GLP-1/GIP receptor agonists in preconception, pregnancy, and lactation: a systematic review of maternal, fetal, and neonatal outcomes

Abstract

Background and Aim Use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists is increasing among reproductive-aged women for obesity, diabetes, polycystic ovary syndrome (PCOS), and cardiometabolic disease. However, the safety of these agents in pregnancy and lactation remains sparse, while inadvertent first-trimester exposure is becoming more common. The aim of this review is to systematically evaluate maternal, fetal, neonatal, and lactation outcomes following preconception, in-pregnancy, or postpartum exposure to GLP-1 and dual GLP-1/GIP receptor agonists.Methods We conducted a systematic review of PubMed/MEDLINE, Web of Science, Scopus, and the Cochrane Library from inception to 23 September 2025. Human studies reporting exposure to GLP-1 or dual GLP-1/GIP receptor agonists during preconception, pregnancy, or lactation were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias using validated tools. Given clinical heterogeneity, findings were synthesised narratively in accordance with PRISMA 2020 guidelines.Results Thirty-six studies met the inclusion criteria. Across large observational cohorts, periconceptional or early-pregnancy exposure to GLP-1-based therapies was not consistently associated with increased risk of major congenital malformations in adjusted analyses, fetal growth restriction, stillbirth, or neonatal mortality compared with insulin-treated or disease-matched controls. Maternal outcomes, including gestational diabetes, hypertensive disorders of pregnancy, preterm birth, and gestational weight gain, were heterogeneous without a reproducible safety signal. Indeed, in women with PCOS, GLP-1RAs seem promising in various aspects. Lactation data were sparseone pharmacokinetic study reported no detectable semaglutide transfer into human milk.Conclusion Current evidence suggests that preconceptional or early-pregnancy exposure to GLP-1-based therapies is not consistently associated with increased maternal, fetal, or neonatal risk, although data on continued use throughout gestation remain limited.