Semaglutide and Liraglutide Linked to Higher-Than-Expected Rates of Gallbladder and Biliary Problems

Researchers extracted adverse event reports from the FDA Adverse Event Reporting System (FAERS) between Q1 2013 and Q1 2024 using OpenVigil 2.1. They used four standard signal detection methods (ROR, PRR, BCPNN, and EBGM) to assess whether biliary adverse events were reported more frequently than expected for these drug classes.

With tens of millions of people now taking GLP-1 receptor agonists, even rare adverse effects can affect large numbers of patients. This analysis raises a safety signal that gallbladder and biliary problems may be more common with semaglutide and liraglutide than previously appreciated, warranting clinical awareness.

Gallbladder problems have been an emerging concern with GLP-1 receptor agonists, potentially related to rapid weight loss or direct effects on gallbladder motility. This pharmacovigilance study adds quantitative evidence from real-world data, joining clinical trial observations that have noted elevated cholecystitis and cholelithiasis rates with these drugs.

FAERS data has well-known limitations: it relies on voluntary reporting (under-reporting is common), cannot establish causation, may be influenced by reporting biases (e.g., higher awareness of GLP-1 RA side effects drives more reports), and lacks denominators to calculate true incidence rates. Confounders like obesity itself (a gallstone risk factor) and rapid weight loss cannot be controlled for in this analysis.