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

Mariana M Ramírez-Mejía; Guadalupe Ponciano-Rodriguez; Mohammed Eslam; Nahum Méndez-Sánchez

doi:10.1177/20420188251406456

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

Ther Adv Endocrinol Metab. 2025 Dec 23:16:20420188251406456. doi: 10.1177/20420188251406456. eCollection 2025.

Authors

Mariana M Ramírez-Mejía^{1

2}, Guadalupe Ponciano-Rodriguez³, Mohammed Eslam⁴, Nahum Méndez-Sánchez⁵

Affiliations

¹ Plan of Combined Studies in Medicine, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
² Liver Research Unit, Medica Sur Clinic and Foundation, Mexico City, Mexico.
³ Public Health Department, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.
⁴ Storr Liver Centre, Westmead Institute for Medical Research, Westmead Hospital and University of Sydney, Westmead, NSW, Australia.
⁵ Liver Research Unit, Medica Sur Clinic and Foundation, 150 Puente de Piedra, Tlalpan, Mexico City 14050, Mexico Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico.

Abstract

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.

Keywords: FXR; GLP-1 receptor agonists; TGR5; bile stasis; cholecystokinin; gallstones.

Plain language summary

GLP-1 receptor agonist medications and gallbladder disease: understanding the mechanisms and what it means for patients Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are commonly used to help people with type 2 diabetes and obesity by improving blood sugar control and promoting weight loss. They work by increasing insulin levels, reducing glucagon (a hormone that raises blood sugar) and slowing digestion. Because of these effects, they are very effective in controlling metabolic conditions. However, while these drugs provide significant benefits, they have also been linked to an increased risk of gallbladder problems, including gallstones (cholelithiasis) and inflammation of the gallbladder (cholecystitis), especially when used for a long time or at high doses. This review examines how GLP-1RAs can affect the gallbladder, including changes in digestive hormones, bile acids, and gut-brain signaling. It also presents a new approach to help physicians manage these risks in patients using these drugs.

Publication types

Review