GLP1-Based Multi-Agonist Therapy for PCOS

Polycystic ovary syndrome (PCOS) is a multifactorial disorder characterized by reproductive and metabolic disturbances, including oligo-/anovulation, hyperandrogenism, and polycystic ovarian morphology. It is frequently associated with obesity, insulin resistance, and type 2 diabetes, all of which substantially increase long-term health risks. Current therapies are primarily symptomatic, offering only partial relief for both metabolic and reproductive dysfunctions.

A recent preclinical study highlights the promise of glucagon-like peptide-1 (GLP1)-based multi-agonists in PCOS management. Investigators compared three therapeutic combinations—GLP1/estrogen (GLP1/E), GLP1/gastric inhibitory peptide (GLP1/GIP), and GLP1/GIP/glucagon—across two mouse models of PCOS with differing reproductive and metabolic profiles. Outcomes were benchmarked against standard metformin therapy.

Among the tested agents, GLP1/E demonstrated superior efficacy in improving metabolic complications and restoring ovarian cyclicity in a model with ovulatory dysfunction. Notably, these benefits were achieved without undesirable estrogenic effects on the uterus. Proteomic analyses also revealed modulation of hypothalamic pathways, suggesting central nervous system mechanisms may underlie the differential efficacy of GLP1/E.

These findings underscore the therapeutic potential of GLP1-based multi-agonists—particularly GLP1/E—as a personalized strategy for addressing the dual metabolic and reproductive challenges of PCOS.

Source: Sánchez-Garrido MA, et al. Nat Commun. 2024 Oct 1;15(1):8498. doi: 10.1038/s41467-024-52898-y.