GLP-1 receptor agonists and gallbladder disease risk: insights into molecular mechanisms and clinical implications

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become essential medications in the management of type 2 diabetes mellitus and obesity due to their ability to improve glucose control and facilitate weight loss by enhancing insulin secretion, reducing glucagon release, and slowing gastric emptying. These mechanisms make GLP-1RAs highly effective for metabolic disorders, benefiting patients who require both glycemic control and weight reduction. However, despite their clinical efficacy, GLP-1RAs have been associated with an increased risk of gallbladder disease, including gallstone formation known as cholelithiasis and inflammation of the gallbladder called cholecystitis, especially with prolonged use and higher doses. This review explores the potential mechanisms by which GLP-1RAs may contribute to biliary disease, focusing on the roles of cholecystokinin suppression, bile acid receptor signaling, and alterations in gut-brain pathways. In addition, we present a novel algorithm designed to outline strategies to address the risks of biliary disease in patients treated with GLP-1RAs.