GLP-1 Receptor Agonist Use Associated with Increased Risk of NAION in Older Adults with Type 2 Diabetes

Use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may be linked to a higher risk of developing nonarteritic anterior ischemic optic neuropathy (NAION) in older adults with type 2 diabetes, according to a research letter published online on July 31 in JAMA Ophthalmology.

The study, led by Kin Wah Fung, M.D., from the National Institutes of Health in Bethesda, Maryland, analyzed data from an observational cohort of Medicare enrollees aged 65 years or older with type 2 diabetes. The researchers compared patients prescribed GLP-1 RAs with those taking other antidiabetic medications, assessing GLP-1 RAs first as a drug class and then individually. Propensity score adjustment was applied to account for baseline differences.

Patient Population and Medication Use

The analysis included 3,845,171 patients with type 2 diabetes, of whom 15.1% were prescribed a GLP-1 RA, including 6.6% who received dulaglutide, 4.9% who received semaglutide, 4.2% who received liraglutide, and 2.1% who received exenatide.

In addition, 34.8% were prescribed metformin, and 21.7% were prescribed insulin. Over a median follow-up of 3.7 years, 7,660 patients (0.2%) developed NAION.

Key Findings

Use of any GLP-1 RA was associated with a 15% increased risk of NAION compared to other second-line antidiabetic medications (hazard ratio [HR], 1.15). The median time from starting GLP-1 RA therapy to NAION diagnosis was 3.3 years.

When evaluating individual agents, the study found an increased risk for NAION with semaglutide, which had a hazard ratio of 1.39, and with liraglutide, which had a hazard ratio of 1.25.

Clinical Implications

The authors emphasize that the potential risk of NAION with GLP-1 RA therapy warrants further investigation, particularly given the growing use of these agents and the significant impact of NAION on vision.

“The risk of NAION warrants further research given the increasing use of GLP-1 RAs and the seriousness of NAION,” the authors noted.

Reference:

Kin Wah Fung et al, GLP-1 RAs and Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Older Patients With Diabetes, JAMA Ophthalmology (2025). DOI: 10.1001/jamaophthalmol.2025.2299