Diabetes Drugs Targeting Incretins Linked to Gallbladder and Liver Problems in FDA Safety Database

This pharmacovigilance study extracted case reports involving incretin therapies and hepatobiliary adverse events from the FDA Adverse Event Reporting System (FAERS) spanning January 2006 to December 2023. Associations were analyzed using reporting odds ratios and empirical Bayesian geometric means. Descriptive analyses characterized demographic and clinical features. Subgroup analyses evaluated specific drug-event associations.

As GLP-1 receptor agonists and DPP-4 inhibitors are prescribed to millions of people worldwide for diabetes (and increasingly for weight loss), understanding their safety profile is critical. This large-scale analysis identifies hepatobiliary events as a potential concern — particularly gallbladder problems — that clinicians should monitor for, especially in patients with pre-existing gallbladder risk factors.

As incretin-based therapies expand beyond diabetes to obesity treatment, their safety profile under broader use becomes increasingly important. This study adds to growing pharmacovigilance signals about gallbladder complications with these drug classes. The finding that rapid weight loss from GLP-1 agonists may contribute to gallstone formation has implications for the millions of people using these drugs for weight management.

FAERS is a spontaneous reporting system subject to reporting bias, underreporting, and the inability to establish causation. Reporting odds ratios cannot account for confounding factors like obesity, rapid weight loss, and diabetes itself — all of which are independent risk factors for gallbladder disease. The study cannot determine incidence rates or absolute risk. Duplicate reports may exist in FAERS data. The Weber effect (increased reporting for newer drugs) could inflate associations for more recently approved agents.