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. 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 ROR025 > 1 and IC025 > 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. Among 348,649 reports, gastrointestinal disorders were the most frequent System Organ Class. Notable signals included tirzepatide with “abdominal pain” (ROR025 = 53.54), liraglutide with “drug ineffective” (ROR025 = 31.14) and “pancreatitis” (ROR025 = 4.24), exenatide with “injection site pain” (ROR025 = 70.14), and albiglutide with “device use error” (ROR025 = 1424.33). Male patients and younger adults (18–44 years) generally showed higher positive reporting rates. 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.
Li et al. (Tue,) studied this question.