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The following is a summary of “Association of Glucagon-like Peptide-1 Receptor Agonists with Optic Nerve and Retinal Adverse Events: A Population-Based Observational Study Across 180 Countries,” published in the May 2025 issue of American Journal of Ophthalmology by Lakhani et al. 

Researchers conducted a retrospective study to explore the association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and ocular adverse events (AEs) in individuals with type 2 diabetes and obesity.  

They reviewed the United States (US) Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) via OpenVigil 2.1 and the World Health Organization’s VigiBase via VigiAccess to identify optic nerve and retinal AEs linked to semaglutide and tirzepatide. The search period spanned from December 2017 for semaglutide and May 2022 for tirzepatide through September 2024. In FAERS, comparisons were made against all other drugs, while in VigiBase, controls included metformin, empagliflozin, dulaglutide, and insulin. Disproportionality analysis used reporting odds ratios (RORs) with 95% CI.  

The results showed semaglutide and tirzepatide represented 76,444 cases (0.59%) in the FAERS, n=12,936,341) and 118,639 cases (0.34%) in VigiBase (n>35,000,000). Semaglutide had elevated odds for ischemic optic neuropathy (ION) (FAERS: ROR=11.12, 95%CI=8.15–15.16; VigiBase: ROR=68.58, 95%CI=16.75–280.67) and diabetic retinopathy (DR) (FAERS: ROR=17.28, 95%CI=13.62–21.91; VigiBase: ROR=7.81, 95%CI=5.60–10.90). Increased risks were also found for retinal and vitreous detachment, hemorrhage, and tear (FAERS: ROR=2.44–5.89, 95%CI=1.70–8.97, all P<0.001, IC025=0.49; VigiBase: ROR=5.49–20.91, 95%CI=2.71–90.11, all P≤0.0001, IC025≥0.53, vs metformin). VigiBase alone linked semaglutide to macular edema (ROR=3.87, 95%CI=1.89–7.92), macular hole (ROR=20.90, 95%CI=2.65–165.01), and papilledema (ROR=6.97, 95%CI=2.53–19.17) (all P≤0.004, lower Limit of the 95% Credibility Interval for the Information Component (IC₀₂₅ ≥0.27). Sensitivity analysis with empagliflozin and dulaglutide confirmed significant associations with ION and DR, while vitreous complications were also significant against dulaglutide. Compared with insulin, semaglutide showed higher odds for ION (ROR=9.84, 95%CI=4.25–22.81, P<0.0001, IC₀₂₅ =0.42). Tirzepatide showed a significant link only with DR in FAERS.  

Investigators concluded that the widespread use of semaglutide and its observed association with ocular AEs underscored the importance of global pharmacovigilance and post-marketing surveillance. 

Source: ajo.com/article/S0002-9394(25)00239-9/fulltext