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

Area of Science:

• Pharmacovigilance
• Gastroenterology
• Endocrinology

Background:

• Biliary adverse events (AEs) are a known concern with glucagon-like peptide-1 receptor agonists (GLP-1RAs).
• However, significant differences in the reporting of these AEs within the GLP-1RA drug class have not been clearly established.

Purpose of the Study:

• To compare the reporting rates of specific biliary outcomes across various GLP-1RAs.
• To identify potential within-class variations in the risk profile of these agents.

Main Methods:

• A disproportionality analysis was conducted using the FAERS database.
• Biliary outcomes (cholelithiasis, cholecystitis, biliary colic, bile duct stone, cholangitis) were compared across semaglutide, tirzepatide, liraglutide, exenatide, and dulaglutide, with semaglutide as the reference.
• Proportional reporting ratios (PRR) and reporting odds ratios (ROR) were calculated, alongside subgroup and sensitivity analyses.

Main Results:

• Analysis of 3460 reports indicated varied reporting for biliary outcomes. Exenatide and tirzepatide had lower reporting for bile duct stones, while exenatide and dulaglutide showed lower reporting for biliary colic.
• Dulaglutide had higher reporting for cholangitis. Exenatide, liraglutide, and tirzepatide showed increased reporting for cholecystitis and cholelithiasis compared to semaglutide.
• Subgroup and sensitivity analyses confirmed heterogeneity, particularly for bile duct stone and biliary colic.

Conclusions:

• Reporting of biliary AEs differs significantly among GLP-1RAs, indicating agent-specific risks.
• These findings underscore the importance of individualized prescribing decisions and patient counseling regarding potential biliary AEs associated with specific GLP-1RAs.