Integrated Evidence from VigiBase and Clinical Trials: A Comprehensive Pharmacovigilance Analysis of Seven Glucagon-Like Peptide 1 Receptor Agonists (GLP-1 RAs).

INTRODUCTION: Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are key therapies for type 2 diabetes and obesity, regulating blood glucose by mimicking endogenous GLP-1. Despite efficacy, GLP-1 RAs are associated with adverse reactions across multiple organ systems. To address the gap in class-wide comparative safety analyses beyond previous studies limited to single drugs or organ systems, this study systematically evaluated adverse events for all approved GLP-1 RAs to identify hidden risks and support clinical decision-making. METHODS: We conducted a disproportionality analysis using the World Health Organization pharmacovigilance database (VigiBase) data up to January 2025. Reporting odds ratio (ROR) and information component (IC) were calculated for seven GLP-1 RAs. Signals were considered significant when ROR > 1 and IC > 0. Subgroup analyses were stratified by gender and age. We aimed to synthesize and analyze existing randomized controlled trials (RCT) to validate VigiBase mining results. RESULTS: Among 348,649 reports, gastrointestinal disorders were the most frequent System Organ Class. Notable signals included tirzepatide with "abdominal pain" (ROR = 53.54), liraglutide with "drug ineffective" (ROR = 31.14) and "pancreatitis" (ROR = 4.24), exenatide with "injection site pain" (ROR = 70.14), and albiglutide with "device use error" (ROR = 1424.33). Male patients and younger adults (18-44 years) generally showed higher positive reporting rates. CONCLUSIONS: This study provides a comprehensive safety comparison across all seven approved GLP-1 RAs, confirming known risks and revealing drug-specific signals-such as injection-related issues and paradoxical hyperglycemia. These findings aid personalized treatment strategies and post-marketing surveillance.