Next-generation incretin therapeutics for polyendocrine metabolic ovarian syndrome: navigating current pipeline and clinical considerations

INTRODUCTION: Polyendocrine metabolic ovarian syndrome (PMOS), formerly known as polycystic ovary syndrome (PCOS), is a complex metabolic-reproductive disorder managed with lifestyle interventions, metformin, and symptom-directed therapies. Incretin-based therapies offer substantial metabolic benefits, but their reproductive efficacy, durability, and phenotypic safety remain incompletely defined. AREAS COVERED: This narrative review examines the therapeutic evolution from single glucagon-like peptide-1 (GLP-1) receptor agonists to dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonism with tirzepatide and triple GIP/GLP-1/glucagon receptor agonism with retatrutide. A structured PubMed search of studies published from January 2023 to October 2026 was supplemented by ClinicalTrials.gov and reference-list screening. Evidence was evaluated across metabolic, hormonal, and reproductive outcomes. EXPERT OPINION: Single GLP-1 receptor agonists, particularly semaglutide, improve weight, adiposity, and insulin resistance, with emerging evidence of reproductive benefits. Multi-incretin therapies may provide greater reductions in body weight, visceral and ectopic fat, and insulin resistance. However, PMOS-specific reproductive evidence remains limited. Whether reproductive benefits are independent of weight loss, persist after treatment withdrawal, or differ across PMOS phenotypes is uncertain. Phenotype-stratified randomized trials with standardized reproductive, metabolic, cardiovascular and safety endpoints are needed to determine whether multi-incretins provide durable benefits beyond weight control while maintaining reproductive safety and accessibility.