Comparative Effects of Metformin and GLP-1 Agonists on Polyendocrine Metabolic Ovary Syndrome and Gallbladder Disease

Abstract

Polyendocrine metabolic ovarian syndrome (PMOS) is a common endocrine disorder affecting 5% to 15% of reproductive-aged individuals and is frequently accompanied by hyperinsulinemia and obesity. These metabolic disturbances contribute to gallbladder dysmotility and increased cholesterol synthesis, elevating the risk of cholelithiasis, cholecystitis, and cholangitis. Metformin is widely used to manage dyslipidemia, type 2 diabetes mellitus, and obesity in patients with PMOS, but emerging therapies such as glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) may offer additional benefit. This study used the TriNetX network to compare the incidence of gallbladder disease between patients with PMOS treated with metformin and those treated with GLP-1 RAs. After 1:1 propensity score matching on age, type 2 diabetes mellitus, obesity, body mass index, and lipid-lowering therapy, two cohorts of 53,258 patients were analyzed. Glucagon-like peptide-1 RAs were associated with a lower incidence of cholelithiasis and cholecystitis than metformin, whereas cholangitis rates were similar. These findings suggest that GLP-1 RAs may confer a protective effect through weight reduction and improved insulin sensitivity. Further study is warranted to confirm the effect of GLP-1 RAs on cholelithiasis and cholecystitis.