The Role of Glp-1 Receptor Agonists in Insulin Resistance with Concomitant Obesity Treatment in Polycystic Ovary Syndrome

Int J Mol Sci. 2022 Apr 14;23(8):4334. doi: 10.3390/ijms23084334.


Insulin resistance is documented in clamp studies in 75% of women with polycystic ovary syndrome (PCOS). Although it is not included in the diagnostic criteria of PCOS, there is a crucial role of this metabolic impairment, which along with hormonal abnormalities, increase each other in a vicious circle of PCOS pathogenesis. Insulin resistance in this group of patients results from defects at the molecular level, including impaired insulin receptor-related signaling pathways enhanced by obesity and its features: Excess visceral fat, chronic inflammation, and reactive oxygen species. While lifestyle intervention has a first-line role in the prevention and management of excess weight in PCOS, the role of anti-obesity pharmacological agents in achieving and maintaining weight loss is being increasingly recognized. Glucagon-like peptide-1 receptor agonists (GLP1-RAs) not only act by reducing body weight but also can affect the mechanisms involved in insulin resistance, like an increasing expression of glucose transporters in insulin-dependent tissues, decreasing inflammation, reducing oxidative stress, and modulating lipid metabolism. They also tend to improve fertility either by increasing LH surge in hypothalamus-pituitary inhibition due to estrogen excess connected with obesity or decreasing too high LH levels accompanying hyperinsulinemia. GLP1-RAs seem promising for effective treatment of obese PCOS patients, acting on one of the primary causes of PCOS at the molecular level.

Keywords: glucagon-like peptide-1 receptor agonists (GLP-1RAs); infertility; inflammation; insulin resistance (IR); lipid metabolism; obesity; oxidative stress; polycystic ovary syndrome (PCOS).

Publication types

  • Review

MeSH terms

  • Anti-Obesity Agents* / therapeutic use
  • Female
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Humans
  • Inflammation / complications
  • Insulin / therapeutic use
  • Insulin Resistance*
  • Obesity / complications
  • Obesity / drug therapy
  • Obesity / metabolism
  • Polycystic Ovary Syndrome* / complications
  • Polycystic Ovary Syndrome* / drug therapy
  • Polycystic Ovary Syndrome* / metabolism


  • Anti-Obesity Agents
  • Glucagon-Like Peptide-1 Receptor
  • Insulin