Cohort Study: Risk of Gallstones and Biliary Complications With Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes.

BACKGROUND

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for type 2 diabetes mellitus (T2DM) because of their benefits in glycemic control, weight reduction, and cardiovascular outcomes. This study evaluated the risk of gallbladder disease among diabetic patients treated with GLP-1 RAs.

METHODS

A retrospective cohort analysis was performed using the TriNetX research network. Adults ≥ 18 years with T2DM who received GLP-1 RAs were identified and compared with matched controls. Propensity score matching (1:1) was used to balance baseline characteristics. Outcomes included cholelithiasis/choledocholithiasis, cholecystitis, pancreatitis, endoscopic retrograde cholangiopancreatography (ERCP), and cholecystectomy. Subgroup analyses were performed according to GLP-1 RA agents.

RESULTS

A total of 156,376 patients were included; 43,077 patients were in the GLP-1 RA cohort and 113,299 patients were in the control group. After matching, 39,140 patients remained in each group. At two years, patients with GLP-1 RA use had higher rates of cholelithiasis/choledocholithiasis (aOR 1.44, 95% CI 1.24-1.65), whereas rates of cholecystectomy were non-significant. By three years, GLP-1 RA use remained associated with higher rates of cholelithiasis/choledocholithiasis (aOR 1.43, 95% CI 1.24-1.63), cholecystitis (aOR 1.45, 95% CI 1.14-1.83), and cholecystectomy (aOR 1.54, 95% CI 1.17-2.02). There were no significant differences in the rates of pancreatitis or ERCP. Semaglutide and dulaglutide demonstrated higher cholelithiasis, whereas liraglutide and exenatide were not associated with a significant increase.

CONCLUSION

GLP-1 RAs use in patients with T2DM was associated with modestly higher rates of cholelithiasis/choledocholithiasis, cholecystitis, and cholecystectomy, whereas there were no significant differences in rates of pancreatitis or ERCP.