Evaluating the Evolving Real-World Adverse Events of GLP-1RAs Using FDA Adverse Event Reporting System (FAERS).

Abstract

This study aimed to assess the spectrum and frequency of adverse events (AEs) linked to glucagon-like peptide-1 receptor agonists (GLP-1RAs) using the US FDA Adverse Event Reporting System (FAERS). Emphasis was placed on emerging safety concerns in context-specific use. A retrospective analysis of FAERS reports between 2012 and 2025 was conducted. Five commonly prescribed FDA-approved GLP-1RAs were included. Disproportionality analyses were applied to detect AE signals. Subgroup analyses evaluated associations by indication, GLP-1RAs compared to other drugs, and AEs specific to individual GLP-1RAs. From over 18 million FAERS reports, 137,451 involved GLP-1RAs. The most frequent AEs were gastrointestinal, nutritional and metabolic, and psychiatric disorders, occurring at higher rates compared to other drugs. In diabetes use, GLP-1RAs were associated with retinopathy, hearing loss, and cataracts. In contrast, when prescribed for weight management/obesity, nutritional, metabolic, and psychiatric AEs predominated. We also developed an open-access portal for AE exploration, available at http://glp1.tanlab.org. GLP-1RAs are linked to a broad range of AEs across indications. These findings stress the need for careful clinical monitoring and long-term safety evaluation. This study also illustrates how real-world evidence can inform safety communications, as well as hypothesis generation for research on next-generation GLP-1RAs.