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

Abstract

ABSTRACT 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. ueg270238-sec-0001 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. ueg270238-sec-0002 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. ueg270238-sec-0003 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. ueg270238-sec-0004 Key Summary Summarize the established knowledge on this subject ◦ Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) are widely used in type 2 diabetes mellitus and have been linked to gallbladder and biliary adverse events. simple What are the significant and/or new findings of this study? ◦ In this large real‐world cohort with up to three years of follow‐up, use of GLP‐1 RA was associated with increased risks of cholelithiasis, choledocholithiasis, cholecystitis and cholecystectomy, without higher rates of pancreatitis or ERCP. ◦ Biliary risk varied by individual GLP‐1 RA agent, with higher cholelithiasis observed with semaglutide and dulaglutide but not with liraglutide or exenatide. ◦ In multivariable analyses, steatotic liver disease, alcohol use, and obesity were independent predictors of gallbladder and biliary events, whereas glycemic control, hyperlipidaemia, and tobacco use were not. simple bullet highlights http://www.w3.org/1999/xlink anchor jats-graphic-1 portrait UEG2-14-e70238-g001.jpg anchor graphic portrait graphical