GLP-1 receptor agonist use in type 2 diabetes was associated with modestly higher gallstone and biliary complication rates but not higher pancreatitis or rates.
Evidence
This TriNetX retrospective matched cohort study compared 39,140 GLP-1 RA users with 39,140 controls and found higher three-year odds of /choledocholithiasis, , and cholecystectomy.
Caveat
Because treatment was not randomized and agent subgroup signals varied, residual confounding and prescribing differences may partly explain the observed biliary risks.
Simplified
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 /choledocholithiasis, , pancreatitis, endoscopic retrograde cholangiopancreatography (), 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.
Key numbers
1.44
Higher Rate of
Adjusted Odds Ratio (aOR) for /choledocholithiasis at two years.
1.45
Increased Risk
Adjusted Odds Ratio (aOR) for at three years.
1.54
Cholecystectomy Rate Increase
Adjusted Odds Ratio (aOR) for cholecystectomy at three years.
Full Text
We can’t show the full text here under this license.
