Type 2 diabetes patients initiating semaglutide, a GLP-1 receptor agonist, are at a higher risk of developing new-onset nonarteritic anterior ischemic optic neuropathy (NAION), a potentially blinding eye condition, compared with those starting sodium-glucose cotransporter-2 inhibitors (SGLT2i) (1). The overall NAION risk, however, remained low over a maximum follow-up of 7.5 years.

This cohort study of US veterans, published recently in JAMA Ophthalmology, investigated whether initiation of semaglutide was associated with an increased risk of new-onset NAION in patients with type 2 diabetes. Using Veterans Health Administration data (2018-2025), investigators emulated a target trial comparing starting semaglutide with a SGLT2i as second-line therapy in metformin-treated adults.  The SGLT2is reviewed included empagliflozin, dapagliflozin, and canagliflozin.

The study included 102,361 US veterans, mean age 60 years with male preponderance (85.5%), comprising 11,478 semaglutide initiators and 90,883 SGLT2i initiators. Groups were balanced using overlap weighting to minimize confounding. The baseline body mass index (BMI) was 37.8 and hemoglobin A1c 7.0%.

A total of 173 incident NAION events were identified through International Classification of Diseases, 10th Revision (ICD-10) and Systematized Nomenclature of Medicine (SNOMED) codes over a maximum follow-up of 7.5 years. The incidence rate of NAION was higher among semaglutide initiators (123 per 100,000 person-years) compared with SGLT2i initiators (67 per 100,000 person-years).

Over a median follow-up of 2.1 years, semaglutide initiators demonstrated more than a twofold increase in the risk of developing NAION compared with those who started an SGLT2 inhibitor, with a hazard ratio of 2.33. The overlap weighted incidence rate of NAION was 0.29% in semaglutide users versus 0.13% in SGLT2i users, corresponding to an average treatment effect of 0.16 percentage points.

The study concluded that semaglutide initiation was associated with an increased risk of new-onset NAION. Although the absolute risk is small, “NAION has emerged as a serious rare adverse event”, note the authors. Hence, clinicians should also counsel patients regarding this potential “vision-loss event” while discussing the cardiometabolic benefits of semaglutide and if prescribed, be vigilant for any visual symptoms, particularly in patients with ocular risk factors such as optic nerve disease.

Reference

1.    Heberer K, et al. New-onset nonarteritic anterior ischemic optic neuropathy and initiators of semaglutide in us veterans with type 2 diabetes. JAMA Ophthalmol. 2026 Feb 12:e256262. doi: 10.1001/jamaophthalmol.2025.6262.