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.
Yukesh et al. (Sat,) studied this question.