Nadia J Abbass; Raya Nahlawi; Jacqueline K. Shaia; Kevin Allan; David C. Kaelber; Katherine E. Talcott; Rishi P. Singh · 2025 · American Journal of Ophthalmology
Paper
PURPOSE: The association between GLP-1 receptor agonists (GLP-1RA) and nonarteritic anterior ischemic optic neuropathy (NAION) remains unclear. Given the debilitating sequelae of NAION and rapid increase of GLP-1RA use, further research is essential to investigate this potential relationship. This study seeks to determine the risk of NAION and ischemic optic neuropathy (ION) in patients prescribed GLP-1RAs. DESIGN: Retrospective matched cohort study. SETTING: TriNetX United States collaborative network. PARTICIPANTS: Patients ≥12 years old with type 2 diabetes (T2DM) and considered overweight or obese (high BMI), with at least one ophthalmology or neurology visit. Among T2DM patients, approximately 120,000 patients with a semaglutide prescription and 220,000 prescribed any GLP-1RA were compared to matched T2DM controls. Among high BMI patients, approximately 58,000 on semaglutide and 66,000 on any GLP-1RA were compared to matched controls. METHODS: Patients prescribed semaglutide or any GLP-1RA were compared with those on non-GLP-1RA medications. Populations were propensity matched (1:1) on various demographic and risk factors to balance baseline cohorts. MAIN OUTCOMES AND MEASURES: Cumulative incidence and risk of NAION and ION. Risk ratios (RR) with 95% confidence intervals (CI) were reported, with significance defined as CI 1.1. RESULTS: In T2DM patients prescribed semaglutide, the risk of NAION (RR = 0.7, 95% CI: 0.523-0.937) and ION (RR = 0.788, 95% CI: 0.609-1.102) after 5 years was not significantly increased compared to matched T2DM controls. Similarly, T2DM patients on any GLP-1RA demonstrated no significant difference in the risk of NAION (RR = 0.887, 95% CI: 0.735-1.071) or ION (RR = 0.969, 95% CI: 0.813-1.154) compared to controls. Furthermore, no increased risk of either outcome was found in the high BMI groups prescribed semaglutide or any GLP-1RA. The cumulative 5-year risk of NAION and ION in T2DM patients on semaglutide was 0.065% and 0.08%, respectively. In those with high BMI prescribed semaglutide, the risk of NAION and ION after 2 years was 0.038% and 0.404%, respectively. CONCLUSIONS: There was no significant increase in risk of NAION or ION in patients taking semaglutide or GLP-1RAs compared to T2DM or high BMI controls.
Analysis
This retrospective cohort study found no significant increase in the risk of nonarteritic anterior ischemic optic neuropathy (NAION) or ischemic optic neuropathy (ION) in patients with type 2 diabetes or high BMI treated with semaglutide or other GLP-1 receptor agonists compared to matched controls.
Discovery
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