The Effect of Semaglutide and GLP-1 RAs on Risk of Nonarteritic Anterior Ischemic Optic Neuropathy

Abstract

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 <0.9 or > 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.