Differential Biliary Adverse Event Signals Among Glp-1 Receptor Agonists: A FAERS Disproportionality Analysis

Biliary adverse events (AEs) have been reported with glucagon-like peptide-1 receptor agonists (GLP-1RAs), but within-class differences remain unclear.

We conducted a disproportionality analysis of FAERS comparing biliary outcomes (cholelithiasis, cholecystitis, biliary colic, bile duct stone, and cholangitis) across semaglutide, tirzepatide, liraglutide, exenatide, and dulaglutide; semaglutide was used as the reference agent. Proportional reporting ratios (PRR), reporting odds ratios (ROR), 95% confidence intervals, and Fisher exact tests were calculated. Subgroup analyses and sensitivity analyses were performed.

After deduplication, 3460 reports were analyzed: semaglutide 1797, tirzepatide 1363, liraglutide 1033, exenatide 999, and dulaglutide 574. Compared with semaglutide, exenatide and tirzepatide showed lower reporting for bile duct stone (PRR 0.39 and 0.58), while exenatide and dulaglutide showed lower reporting for biliary colic (PRR 0.30 and 0.50). Dulaglutide showed higher reporting for cholangitis (PRR 1.65). Exenatide, liraglutide, and tirzepatide showed higher reporting for cholecystitis (PRR 1.12, 1.07, and 1.05) and cholelithiasis (PRR 1.33, 1.21, and 1.15). Subgroup findings were consistent with heterogeneity mainly observed for bile duct stone and biliary colic. Sensitivity analyses was largely concordant, although rarer outcomes lost significance.

Biliary AE reporting varies across GLP-1RAs, highlighting agent-specific differences within class and the need for individualized prescribing and counseling.