Regional Differences in GLP-1 Receptor Agonists Related Biliary Disease: A Pharmacovigilance Study of VigiBase®

Abstract

Glucagon-like peptide-1 receptor agonists are highly recommended for treatment of type 2 diabetes as one of the second-line therapies with additional benefits of cardiorenal disease. Despite the diverse therapeutic advantages, safety issues remain controversial regarding the pancreatic-related adverse events associated with the use of incretin-based drugs. We aimed to examine regional differences in biliary diseases related safety for GLP-1 RAs compared with all other antidiabetic drugs. In this study, individual case safety reports for GLP-1 RAs and comparison group were retrieved from the World Health Organization’s global database, VigiBase during 2005 to 2023. Disproportionality analysis was performed to examine Reporting odds ratio and 95% confidence interval for each adverse event of interest, adjusted for sex and age group by using logistic regression. Disproportionate reporting was observed in America for biliary track disorders associated with the GLP-1 RAs compared with all other antidiabetic drugs. However, for gallbladder-related disorders, an increased risk was identified in most regions (America: ROR 2.34; 95%CI 2.06-2.66, Europe: ROR 5.71; 4.62-7.05, Asia: ROR 4.12; 2.98-5.69). As this study cannot determine the causality between GLP-1 RAs and the biliary disease, a multinational confirmatory study is inevitable to validate the regional differences in the association between GLP-1 RAs and biliary disease.