GLP-1RAs exhibit varied biliary adverse event reporting, with exenatide and dulaglutide showing lower colic risk

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective for type 2 diabetes and obesity, but concerns exist regarding biliary adverse events (AEs) like cholelithiasis and cholecystitis. While these AEs are generally attributed to rapid weight loss, within-class differences among GLP-1RAs in their propensity to cause specific biliary issues remain poorly understood. Understanding these distinctions is crucial for individualized patient counseling and prescribing, as current guidelines often treat GLP-1RAs as a homogenous class for this risk.

Researchers conducted a disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) database to compare biliary outcomes across five GLP-1RAs: semaglutide, tirzepatide, liraglutide, exenatide, and dulaglutide. Semaglutide was used as the reference agent for comparison. The study calculated proportional reporting ratios (PRR), reporting odds ratios (ROR), 95% confidence intervals, and Fisher exact tests for biliary outcomes including cholelithiasis, cholecystitis, biliary colic, bile duct stone, and cholangitis. Subgroup and sensitivity analyses were also performed to assess consistency.

After deduplication, a total of 3460 reports were analyzed, with semaglutide accounting for 1797, tirzepatide for 1363, liraglutide for 1033, exenatide for 999, and dulaglutide for 574. Significant differential reporting was observed across the GLP-1RA class for various biliary events. Compared with semaglutide, exenatide and tirzepatide showed lower reporting for bile duct stone (PRR 0.39 and 0.58, respectively). Similarly, exenatide and dulaglutide demonstrated lower reporting for biliary colic (PRR 0.30 and 0.50). Conversely, dulaglutide exhibited higher reporting for cholangitis (PRR 1.65).

Exenatide, liraglutide, and tirzepatide consistently showed higher reporting for both cholecystitis (PRR 1.12, 1.07, and 1.05) and cholelithiasis (PRR 1.33, 1.21, and 1.15) compared to semaglutide. Subgroup findings largely aligned with the main results, though heterogeneity was noted for bile duct stone and biliary colic.