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

Background: Biliary adverse events (AEs) have been reported with glucagon-like peptide-1 receptor agonists (GLP-1RAs), but within-class differences remain unclear. Methods: 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. Results: After deduplication, 3,460 reports were analyzed: semaglutide 1,797, tirzepatide 1,363, liraglutide 1,033, exenatide 999, and dulaglutide 574. Compared with semaglutide, exenatide (PRR 0.39 (0.23–0.65) p<0.001) and tirzepatide (PRR 0.58 (0.39–0.84), p= 0.004) showed lower reporting for bile duct stone, while dulaglutide (PRR 0.50 (0.30–0.82), p=0.003) and exenatide (PRR 0.30 (0.19–0.47), p<0.001) showed lower reporting for biliary colic (PRR 0.30 and 0.50). Dulaglutide showed higher reporting for cholangitis (PRR 1.65 (1.05–2.60), p=0.045). Exenatide (PRR 1.12 (1.08–1.16), p<0.001), liraglutide (PRR 1.07 (1.03–1.12), p<0.001), and tirzepatide (PRR 1.05 (1.01–1.09), p=0.018) showed higher reporting for cholecystitis . Exenatide (PRR 1.33 (1.23–1.44), p<0.001), liraglutide (PRR 1.21 (1.11–1.31), p<0.001) and tirzepatide (PRR 1.15 (1.06–1.25), p<0.001) also showed higher reporting for cholelithiasis . Subgroup findings were consistent with heterogeneity mainly observed for bile duct stone and biliary colic. Sensitivity analyses were largely concordant, although rarer outcomes lost significance. Conclusions: Biliary AE reporting varies across GLP-1RAs, highlighting agent-specific differences within class and the need for individualized prescribing and counseling.