Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes.

Background: Nonarteritic anterior ischemic optic neuropathy (NAION) is an untreatable condition often causing severe and irreversible visual loss in the affected eye. As it has recently been implied that the use of semaglutide associates with NAION, the aim of the present study was to evaluate this risk prospectively in all persons with type 2 diabetes (T2D) in Denmark.

Methods: In a five-year longitudinal cohort study, we identified all persons with T2D in Denmark (n = 424,152) between 2018 and 2024. Patients were stratified according to exposure (n = 106,454) or non-exposure (n = 317,698) to once-weekly semaglutide, and incidence rates and hazard ratios (HR) of NAION were estimated in a multivariable Cox proportional hazard regression model.

Results: At baseline, median age and hemoglobin A1c were 65 years and 50 mmol/mol, and 54·5% were male. During 1,915,120 person-years of observation, 218 persons developed NAION. Semaglutide exposure was associated with a higher incidence rate (0·228 vs. 0·093 per 1000 person-years, p < 0·001) and independently predicted a higher risk of upcoming NAION (HR 2·19, 95% confidence interval 1·54 - 3·12), even when multiple other factors were taken into account. Overall, 67 persons exposed to semaglutide developed NAION with a median time from first prescription to event of 22·2 months (interquartile range 10·2-37·8 months).

Conclusions: During five years of observation of all persons with T2D in Denmark, use of once-weekly semaglutide independently more than doubled the risk of NAION. Given the irreversible nature of NAION, it is important to acknowledge this risk, and upcoming studies should aim to identify high-risk subgroups.