Disproportionality analysis on glucagon-like peptide-1 receptor agonists and retinal detachment: Insights from the FDA adverse event reporting system

Abstract Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used for Type 2 diabetes mellitus and obesity. Recent reports suggest possible severe ocular adverse effects, including Retinal Detachment (RD). This study aimed to evaluate whether RD is disproportionately reported with GLP-1 RAs and to compare safety signals among six Food and Drug Administration-approved GLP-1 RAs. Methods: A retrospective disproportionality analysis was performed using the FDA Adverse Event Reporting System (FAERS) through July 29, 2025. A case/noncase methodology was applied, and data extraction was performed using OpenVigil 1.0.3. Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) were calculated. A Signal of Disproportionate Reporting (SDR) was defined using Evans’ criteria: ≥3 reports, χ 2 ≥ 4, PRR ≥ 2, and lower 95% confidence interval (CI) of ROR > 1. Results: Among 19,346,589 FAERS reports, 8460 involved RD. Semaglutide demonstrated a clear SDR with 76 RD reports (ROR 3.01, 95% CI 2.42–3.75; PRR 3.0; χ 2 = 98.30). The remaining GLP-1 RAs did not meet SDR criteria: Dulaglutide (44 reports; ROR 1.22; PRR 1.2; χ 2 = 1.51), liraglutide (32 reports; ROR 1.52; PRR 1.5; χ 2 = 5.11), tirzepatide (24 reports; ROR 0.63; PRR 0.6; χ 2 = 4.53), exenatide (24 reports; ROR 0.84; PRR 0.8; χ 2 = 0.52), and lixisenatide (1 report; ROR 0.74; PRR 0.7; χ 2 = 0.01). Conclusion: Only semaglutide showed a statistically significant SDR for RD, suggesting a possible drug-specific safety signal. While causality cannot be inferred, these findings highlight the need for increased ophthalmic monitoring, particularly in patients with underlying retinal disease when starting semaglutide.