GLP-1 Receptor Agonists and Gallbladder Disease: UEG Journal | June 2026

Introduction:

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become a cornerstone in the management of type 2 diabetes because of their excellent glycemic, cardiovascular, and weight-loss benefits. However, concerns remain regarding their potential association with gallbladder and biliary diseases.

Why was this study needed?

Previous studies suggested a possible increase in gallbladder complications with GLP-1 RAs, but long-term real-world data evaluating individual biliary outcomes and differences between specific GLP-1 agents have been limited.

What did the study show?

• This large real-world cohort included over 156,000 patients with type 2 diabetes, with follow-up extending to three years.
• GLP-1 RA therapy was associated with higher risks of cholelithiasis, choledocholithiasis, cholecystitis, and subsequent cholecystectomy.
• No significant increase was observed in acute pancreatitis or the need for ERCP.
• The biliary risk varied among individual agents, with semaglutide and dulaglutide showing a higher risk of gallstones, whereas liraglutide and exenatide were not significantly associated with increased risk.
• Steatotic liver disease, obesity, and alcohol use independently increased the likelihood of gallbladder and biliary complications.

Clinical Impact:

The overall benefits of GLP-1 RAs continue to outweigh these modest biliary risks for most patients. Clinicians should remain vigilant in individuals with pre-existing gallstones, steatotic liver disease, obesity, or heavy alcohol use, and promptly evaluate new biliary symptoms during treatment.

Take-Home Message:

GLP-1 receptor agonists remain highly effective therapies for type 2 diabetes, but they are associated with a modest increase in gallbladder and biliary complications. Careful patient selection, counseling, and monitoring can help maximize benefits while minimizing biliary adverse events.