Pancreaticobiliary side effects of GLP-1 agonists: a meta-analysis of published randomized control trials and a real-world pharmacovigilance profile

To the Editor, Glucagon-like peptide-1 receptor agonists (GLP-1 RA) is a key therapeutic management strategy for obesity1,2. Concerns have arisen regarding the pancreaticobiliary side effects of GLP-1 RA, especially with non-licensed use or use in patient cohorts beyond traditional trial populations3,4. The aim of this meta-analysis was to determine the incidence rate of pancreaticobiliary side effects of GLP-1 RA within RCTs and to compare the incidence to world-wide patient-level data. This meta-analysis was prospectively registered on PROSPERO (ID: CRD420251018806) and reported in accordance to PRISMA5. The primary outcome measure was the incidence of Pancreaticobiliary events following GLP-1 RAs use. The secondary outcome measure was individual biliary and pancreatic events. Pancreaticobiliary events serves as a composite measure of both biliary and pancreatic events. Pancreatic events were defined as episodes of acute pancreatitis or hyperamylasaemia. Biliary events were defined as symptomatic gallstones with episodes of biliary colic, cholecystitis, or if included studies recorded side-effect symptoms attributed to biliary disease. A Bayesian hierarchical logistic regression was constructed and subsequently fitted to the data. To explore real-world data trends of GLP-1 RAs use, publicly available adverse drug event databases were explored. Further methodological details are available in the Supplementary material.