Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy Risk Among Patients With Diabetes

Importance Recent studies have suggested an association between nonarteritic anterior ischemic optic neuropathy (NAION) with semaglutide usage. However, the limitations of those analyses warrant further investigation, given the frequency of use of these medications in people with and without diabetes. Objective To investigate the association between semaglutide use and the risk of NAION among patients with diabetes. Design, Setting, and Participants This cohort study used data from the TriNetX database between October 1, 2019, and December 31, 2023, to identify patients with diabetes with no history of NAION who were prescribed semaglutide. The semaglutide cohort was compared with a control group of randomly selected patients with diabetes who were prescribed non–glucagonlike peptide 1 (non–GLP-1) receptor agonist (RA) antidiabetic medications. The data analysis for this study was performed on September 1, 2024. Exposures Semaglutide history, identified using diagnostic codes. Main Outcomes and Measures Cumulative incidence and (HR) hazard ratio of NAION. Results A total of 3 344 205 patients with diabetes were included in this study. Regarding the diabetes cohort, a total of 174 584 patients with diabetes who received semaglutide (mean [SD] age, 58.3 [12.5] years; 90 427 female [51.8%]; 71 739 male [41.1%]) and 174 584 patients with diabetes who received non–GLP-1 RA medications (mean [SD] age, 58.2 [14.3] years; 90 475 female [51.82%]; 71 989 male [41.24%]) were recruited. Patients with diabetes taking semaglutide exhibited an absence of NAION risk at the 1-month (HR, 2.99; 95% CI, 0.31-28.75), 3-month (HR, 1.33; 95% CI, 0.30-5.93), 6-month (HR, 1.79; 95% CI, 0.60-5.35), and 1-year (HR, 1.94; 95% CI: 0.93-4.02) time points after the index date. However, those taking semaglutide were found to have an increased risk for NAION at the 2-year (HR, 2.39; 95% CI, 1.37-4.18), 3-year (HR, 2.44; 95% CI, 1.44-4.12), and 4-year (HR, 2.05; 95% CI, 1.26-3.34) time points from the index date. Increased risk for NAION was also noted in patients with diabetes and concomitant hypertension who were taking semaglutide (HR, 2.42; 95% CI, 1.19-4.92). An increased NAION risk was also observed among patients with diabetes who had a history of Ozempic (Novo Nordisk) use or stand-alone Ozempic (Novo Nordisk) prescription history. Conclusions and Relevance Results of this cohort study suggest that semaglutide use was associated with an increased risk of NAION in patients with diabetes. However, the study’s retrospective design presents limitations, as it can only infer associations rather than establish causality; further studies are needed.