GLP-1 receptor agonists and preconception planning: bridging the gap between obesity treatment and reproductive safety, a narrative review.

BACKGROUND

Obesity and associated metabolic disorders such as type 2 diabetes mellitus and polycystic ovary syndrome are rising globally, contributing to infertility and adverse pregnancy outcomes. This review synthesizes current evidence on pharmacokinetics, safety in preconception and early pregnancy, and clinical management strategies for glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in women of reproductive age. Ethical and health system considerations are also explored to inform clinical practice and highlight future research priorities.

METHODS

A comprehensive search of PubMed, Scopus, Web of Science, and Google Scholar identified 132 articles. After screening and full-text review, 9 studies met the inclusion criteria for synthesis.

RESULTS

Semaglutide (~7 days) and tirzepatide (~5 days) have long half-lives, requiring discontinuation at least 35 days and 25-35 days, respectively, before conception, while liraglutide requires ≥3 days. Human data show no significant increase in congenital anomalies with inadvertent early exposure, although evidence is limited and observational. Alternatives such as metformin, lifestyle modification, and bariatric surgery remain safer options.

CONCLUSION

GLP-1 RAs may aid preconception metabolic optimization; however, evidence remains limited and largely observational. Preconception discontinuation timed to each agent's half-life is prudent to minimize potential fetal exposure. Prospective studies and pregnancy registries are needed to confirm reproductive safety and refine guidance.