Study Links Semaglutide to Increased NAION Risk in Diabetes Patients

Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is widely prescribed for managing type 2 diabetes and obesity. It offers well-documented benefits in glycemic control and weight reduction. However, emerging evidence raises concerns about its potential ocular side effects, particularly its association with nonarteritic anterior ischemic optic neuropathy, a condition characterized by sudden vision loss due to impaired blood flow to the optic nerve.

Recent studies have suggested a possible link between semaglutide use and NAION. However, given the limitations of these analyses, further research is needed to understand this association better, especially considering the widespread use of these medications in individuals with and without diabetes. Considering this, Alan Y. Hsu, Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan, and colleagues aimed to examine the potential link between semaglutide use and the risk of NAION in patients with diabetes.

For this purpose, the researchers analyzed TriNetX database data from October 1, 2019, to December 31, 2023, to explore the link between semaglutide use and NAION risk in diabetes patients. The study included individuals with diabetes, no prior NAION history, and a semaglutide prescription, comparing them to a control group on non–GLP–1 RA antidiabetic medications. Semaglutide exposure was identified via diagnostic codes, with cumulative NAION incidence and hazard ratio (HR) as primary outcomes. Data analysis was conducted on September 1, 2024.

The key findings of the study were as follows:

• The study included 3,344,205 patients with diabetes.
• A total of 174,584 patients on semaglutide (mean age 58.3 years) and an equal number on non–GLP–1 RA medications (mean age 58.2 years) were analyzed.
• No significant NAION risk was observed in semaglutide users at 1 month (HR 2.99), 3 months (HR 1.33), 6 months (HR 1.79), or 1 year (HR 1.94) after starting treatment.
• An increased risk of NAION was noted in semaglutide users at 2 years (HR 2.39), 3 years (HR 2.44), and 4 years (HR 2.05) after treatment initiation.
• Patients with diabetes and hypertension on semaglutide had a higher risk of NAION (HR 2.42).
• There was also an increased NAION risk in patients with a history of Ozempic (Novo Nordisk) use or a stand-alone Ozempic prescription.

The study findings suggest a possible link between semaglutide use and an increased risk of NAION in patients with diabetes. However, the authors emphasize that the retrospective design of the analysis limits the ability to establish causality. Further research is needed to confirm these findings and explore the underlying mechanisms.

Reference:

Hsu AY, Kuo H, Wang Y, et al. Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy Risk Among Patients With Diabetes. JAMA Ophthalmol. Published online March 27, 2025. doi:10.1001/jamaophthalmol.2025.0349