# The Effects of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists on Polycystic Ovarian Syndrome: A Scoping Review

## TL;DR

This review explores how GLP-1 receptor agonists and related drugs may help treat polycystic ovarian syndrome by improving insulin resistance and weight loss.

## Contribution

The paper introduces and evaluates new incretin mimetics, including dual and triple agonists, as potential treatments for PCOS.

## Key findings

- GLP-1 receptor agonists, dual agonists, and triple agonists improved weight loss and insulin sensitivity in PCOS patients.
- Dual and triple agonists showed greater benefits than GLP-1 agonists alone due to GIP upregulation.
- Some studies reported improvements in PCOS-specific symptoms like dysmenorrhea and ovarian morphology.

## Abstract

Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy in reproductive-aged women worldwide; however, treatment modalities often lack cohesion due to its multifactorial pathophysiology. PCOS is suspected of inducing insulin resistance. Research has explored the use of newly developed incretin mimetics as standard therapy for insulin resistance in insulin-dependent tissues associated with PCOS. The aim of this review was to explore the classes of incretin mimetics, such as glucagon-like peptide-1 (GLP-1) receptor agonists or semaglutide, dual agonists of the GLP-1 receptor and gastric inhibitory peptide (GIP) or tirzepatide, and a new triple agonist, or retatrutide (which is currently seeking Food and Drug Administration (FDA) approval), and their suggested benefits as a treatment for PCOS. A literature review was conducted using EBSCO Medline and PubMed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All three classes of incretin mimetics showed significant improvement in weight loss and insulin sensitivity when compared to traditional pharmacological management with metformin and estradiol-progesterone combination pills in patients with PCOS. The added upregulation of GIP in dual-acting and triple-acting agonists, such as tirzepatide and retatrutide, respectively, resulted in greater reductions in weight loss and insulin sensitivity when compared to medications that acted at the GLP-1 receptor alone. Some research demonstrated symptom improvements specific to PCOS presentation, such as dysmenorrhea and the classic dysmorphic ovarian morphology. Further research is warranted to determine the exact mechanism behind how incretin mimetics may improve the hormonal dysregulation in patients with PCOS, as well as how to best use these medications in conjunction with the current standard of care treatments.