Key Takeaways

  • The FDA is requiring NAION risk warnings in the labeling of all GLP-1 receptor agonists

  • A meta-analysis of 126 clinical trials found NAION incidence rates of 6.4 versus 3.8 cases per 100,000 person-years among GLP-1 RA and comparator groups, respectively

  • Clinicians should promptly refer patients with suspected NAION for ophthalmic evaluation and consider discontinuing GLP-1 RA treatment

The FDA is requiring updated safety labeling for all glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications following an evaluation identifying a potential increased risk of nonarteritic anterior ischemic optic neuropathy (NAION), a rare condition that can cause sudden, painless vision loss.

The agency is directing application holders to add information about NAION to the "Warnings and Precautions" section of product labeling. The decision follows a comprehensive review of clinical trials, observational studies, postmarketing reports, and animal data.

In July 2024, Hathaway et al. published an article titled “Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide.”[1]  Although FDA identified several limitations of this study, the agency determined that further assessment of the potential increased risk for NAION was warranted.

An article published in Ophthalmology in 2024 found that there was a higher risk of NAION in patients prescribed semaglutide compared with patients prescribed non–glucagon-like peptide receptor agonist medications for diabetes or obesity.1 Although the FDA identified several limitations of this study, the agency determined that further assessment of the potential increased risk for NAION was warranted. Therefore, FDA undertook a comprehensive evaluation of clinical trial data, animal data, and postmarketing data, including observational studies and case reports.  

In a meta-analysis of 126 randomized controlled trials involving 134,253 patients, the FDA identified 15 probable NAION events, including 10 among GLP-1 RA recipients and 5 among comparator-treated patients. The incidence was 6.4 cases per 100,000 person-years among GLP-1 RA users compared with 3.8 cases per 100,000 person-years among patients receiving placebo or other glucose-lowering medications.

The FDA also conducted a retrospective cohort study using its Sentinel Real-World Evidence Data Enterprise. Among adults with type 2 diabetes, GLP-1 RA use was associated with a significantly increased NAION risk compared with dipeptidyl peptidase-4 inhibitors (hazard ratio [HR], 1.43; 95% CI, 1.02–2.01). However, the increased risk was not statistically significant compared with sodium-glucose cotransporter-2 inhibitors (HR, 1.19; 95% CI, 0.91–1.54).

Although NAION cases have been reported with all currently marketed GLP-1 RAs, the FDA's review of animal data did not identify a potential mechanism underlying the association.

NAION is caused by decreased blood flow to the optic disc, but the underlying cause is not completely understood. Risk factors may include smoking, diabetes, high blood pressure, sleep apnea, anemia, and kidney disease. If NAION has occurred in one eye, there is an increased risk that it will occur in the other eye.

The agency advises health care professionals to instruct patients to report sudden, painless monocular vision loss, visual field defects, or other visual disturbances immediately. Patients with suspected NAION should be promptly referred to an ophthalmologist.

For patients who develop NAION, clinicians should consider discontinuing GLP-1 RA therapy unless the treatment benefits clearly outweigh the potential risks, the FDA advises.

Earlier this year, Joseph J. Allen, OD, FAAO, Dipl ABO, provided an overview of the potential ocular side effects associated with GLP-1s.

Reference

1. Hathaway JT, Shah MP, Hathaway DB, et al. Risk of nonarteritic anterior ischemic optic neuropathy in patients prescribed semaglutide. JAMA Ophthalmol. 2024;142(8):732-739. doi:10.1001/jamaophthalmol.2024.2296