GLP-1–Based Multi-Agonists Show Promise in Managing PCOS Metabolic and Reproductive Complications

Polycystic ovary syndrome (PCOS) is a multifaceted disorder marked by reproductive and metabolic disturbances such as oligo-/anovulation, hyperandrogenism, polycystic ovaries, obesity, insulin resistance, and type 2 diabetes. Current therapies remain largely symptomatic and provide only partial relief, highlighting the need for novel approaches.

A recent study explored the potential of glucagon-like peptide-1 (GLP-1)–based multi-agonists as therapeutic agents for PCOS. Researchers tested three candidates—GLP-1/Estrogen (GLP-1/E), GLP-1/gastric inhibitory peptide (GLP-1/GIP), and GLP-1/GIP/Glucagon—in two distinct mouse models of PCOS that expressed varying reproductive and metabolic traits, and compared outcomes with standard metformin therapy.

Among the agents tested, GLP-1/E demonstrated the greatest efficacy, surpassing both metformin and other GLP-1–based agonists in improving metabolic dysfunction. It also restored ovarian cyclicity in a PCOS model with ovulatory impairment, without eliciting adverse estrogenic effects on the uterus. Proteomic analyses revealed alterations in hypothalamic pathways, suggesting that GLP-1/E’s central actions may underlie its superior outcomes across different PCOS phenotypes.

These findings highlight the potential of GLP-1–based multi-agonists—particularly GLP-1/E—as a personalized treatment strategy to address both metabolic and reproductive dimensions of PCOS.

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