Semaglutide May Increase Nonarteritic Anterior Ischemic Optic Neuropathy Risk

A recent retrospective cohort study conducted in Taiwan indicated a connection between semaglutide treatment and nonarteritic anterior ischemic optic neuropathy (NAION) risk in patients with diabetes.

“Because NAION is a potentially debilitating ophthalmic condition, gaining a clearer understanding of its incidence and the factors influencing its occurrence would enhance care for those considering the use of these medications,” wrote Alan Y. Hsu, MD, department of ophthalmology, China Medical University, and colleagues.1

Hsu and colleagues indicated that the study was initially proposed due to a lack of research surrounding semaglutide’s potential risk of NAION incidence. Studies such as one conducted by Hathaway et al2 were able to draw a connection between semaglutide treatment and NAION but were likewise unable to indicate a causal relationship.

The team collected its data from the TriNetX analytics platform. The study focused on patients with diabetes ≥12 years of age who were treated with either semaglutide or non-glucagonlike peptide 1 (non-GLP-1) receptor agonists (RAs) between 2019 and 2023.

The initial number of patient records collected was 3,344,205; after excluding those with a history of semaglutide usage, optic neuritis, giant cell arteritis, and NAION diagnoses before first prescription, the total was reduced to 349,168 patients with diabetes. Of this number, 174,584 patients had received a form of semaglutide and 174,584 had received non-GLP-1 RA medications.1

The team discovered no increased risk in semaglutide recipients at the 1-month (hazard ratio [HR], 2.99; 95% CI, .21-28.75; P = .26), 3-month (HR, 1.33; 95% CI, .30-5.93; P = .23), 6-month (HR, 1.79; 95% CI, .60-5.35; P = .37), and 1-year time points (HR, 1.94; 95% CI, .93-4.02; P = .26) compared to non-GLP-1 RA medication recipients.

Increased risk was discovered, however, at the 2-year (HR, 2.39; 95% CI, 1.37-4.18; P = .11), 3-year (HR, 2.44; 95% CI, 1.44-4.12; P = .21), and 4-year (HR, 2.05; 95% CI, 1.26-3.34; P = .71) periods compared to non-GLP-1 RA recipients. Cumulatively, an increased NAION risk was associated with semaglutide use among patients with diabetes (HR, 2.22; 95% CI, 1.37-3.60; P = .58).1

Subgroup analysis indicated that female patients and those within the 40-64 age range had a greater risk of NAION when prescribed semaglutide (HR, 3.31; 95% CI, 1.68-6.53) than other non-GLP-1 RAs. Interestingly, patients with hypertensive disease had an increased risk (HR, 2.42; 95% CI, 1.19-4.92), while those with obesity, concomitant lipoprotein disorder, sleep apnea, ischemic heart disease, and hypothyroidism showed no increased risk for NAION compared to recipients of non-GLP-1 RAs.1

Additionally, subgroups of different semaglutide brands exhibited different levels of NAION incidence. Patients with diabetes who were prescribed Ozempic (HR, 6.27; 95% CI, 2.92-13.47) or had a history of usage (HR, 2.47; 95% CI, 1.50-4.09) exhibited an increased risk, while those using Rybelsus (HR, 1.31; 95% CI, 0.34-5.10) or Wegovy (HR, 2.13; 95% CI, 0.11-41.43) or who had a history of using Rybelsus (HR, 1.56; 95% CI, 0.54-4.52) or Wegovy (HR, 7.52; 95% CI, 0.44-128.80) had no increased risk when compared to non-GLP-1 RA recipients.1

Semaglutide is the only GLP-1 RA currently available in oral form. The team suggests that its safety profile is insufficiently investigated, particularly in relation to NAION risk. NAION’s prevalence and the sudden unilateral vision loss it can cause, the team argues, requires further study of potential triggers, such as semaglutide.1

“This study’s retrospective design can only infer associations rather than establish causality, and other limitations warrant future, carefully designed observational studies to explore this association further,” wrote Hsu and colleagues.1

References

1. Hsu AY, Kuo H-T, Wang Y-H, et al. Semaglutide and nonarteritic anterior ischemic optic neuropathy risk among patients with diabetes. JAMA Ophthalmology. Published online March 27, 2025. doi:10.1001/jamaophthalmol.2025.0349

2. Hathaway JT, Shah MP, Hathaway DB, et al. Risk of nonarteritic anterior ischemic optic neuropathy in patients prescribed SEMAGLUTIDE. JAMA Ophthalmology. 2024;142(8):732. doi:10.1001/jamaophthalmol.2024.2296