6D-09 - Disproportionality Analysis of Adverse Events Associated with GLP-1 Receptor Agonists: Insights from FAERS Data from 2015 to 2024

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for type 2 diabetes and obesity management. However, their safety profile remains a topic of interest, particularly concerning metabolic, gastrointestinal, and systemic adverse effects.

Objectives: This study aims to characterize the disproportionality of adverse event (AE) reporting associated with GLP-1 RAs using the U.S. FDA Adverse Event Reporting System (FAERS).

Methods: A disproportionality analysis was conducted using FAERS from 2015 to 2024 to evaluate the association between GLP-1 RAs and AEs. Individual case safety reports (ICSRs) for exenatide, dulaglutide, lixisenatide, liraglutide, semaglutide, and tirzepatide were analyzed. The primary outcome was AE occurrence, classified by system organ class (SOC) using the Medical Dictionary for Regulatory Activities (MedDRA). The reporting odds ratio (ROR) and 95% confidence interval (CI) were calculated to assess disproportionality. A positive signal was defined as a lower confidence limit (LCL) >1.0. The ROR compared AE odds for GLP-1 RAs versus all other drugs in FAERS. Data analysis was performed using SAS 9.4.

Results: GLP-1 RAs exhibited significant disproportionality signals across multiple SOCs. The highest signal was observed for metabolism and nutrition disorders (ROR: 2.27, 95% CI: 2.24–2.30), followed by product issues (ROR: 2.22, 95% CI: 2.19–2.25) and gastrointestinal disorders (ROR: 2.00, 95% CI: 1.98–2.02). Other SOCs with increased disproportionality included investigations (ROR: 1.89, 95% CI: 1.87–1.91), injury, poisoning, and procedural complications (ROR: 1.65, 95% CI: 1.64–1.67), general disorders and administration site conditions (ROR: 1.07, 95% CI: 1.06–1.08), and endocrine disorders (ROR: 1.05, 95% CI: 1.00–1.10). The findings suggest potential metabolic and gastrointestinal safety concerns, warranting further investigation.

Conclusions: The disproportionality signals observed for GLP-1 RAs emphasize the need for continued post-market surveillance to monitor potential safety concerns that may align with known pharmacological effects. Further research is needed to assess causality and clinical relevance. With risk-benefit considerations, it is warranted to have more guidance for regulatory decisions and clinical practice regarding the broader therapeutic use of GLP-1 RAs.