The U.S. Food and Drug Administration (FDA) has required application holders for all glucagon-like peptide-1 receptor agonist (GLP-1 RA) medicines to update product labelling with a warning about a potential increased risk of non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition that can cause sudden, painless vision loss in one eye and may result in permanent visual impairment. The requirement was announced in an FDA Drug Safety Communication published on 9 November 2026.

The requirement covers all FDA-approved GLP-1 RA products

The FDA is requiring application holders to add information about the potential risk of NAION to the Warnings and Precautions section of labelling for all GLP-1 RA medicines. The class is used primarily to treat type 2 diabetes and promote weight loss, with additional approved uses for certain products involving cardiovascular risk reduction, reduction of the risk of worsening kidney disease and kidney failure in patients with type 2 diabetes and chronic kidney disease, obstructive sleep apnoea and metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis.

The FDA list includes exenatide (originally marketed as Byetta; generic exenatide products remain marketed), liraglutide (Victoza and Saxenda), dulaglutide (Trulicity), liraglutide/insulin degludec (Xultophy), lixisenatide/insulin glargine (Soliqua), semaglutide (Ozempic, Rybelsus and Wegovy), tirzepatide (Mounjaro and Zepbound) and orforglipron (Foundayo). Tirzepatide acts on both GIP and GLP-1 receptors. The FDA notes that the original Byetta application was voluntarily withdrawn in 2025 for reasons unrelated to safety or effectiveness; generic exenatide products remain marketed.

The agency states that NAION cases have been reported in association with all currently marketed GLP-1 RA products.

FDA assessment combines clinical trials and real-world evidence

The FDA began its assessment after a July 2024 observational study by Hathaway et al. in JAMA Ophthalmology examined NAION risk in patients prescribed semaglutide. Although the agency identified limitations in that study, it determined that further assessment was warranted. Its review combined clinical trial data, observational studies, postmarketing reports and animal data.

Analysis of 126 randomised, controlled clinical trials: The FDA meta-analysis included 134,253 participants: 78,217 receiving GLP-1 RAs and 56,036 receiving comparator treatments. The analysis covered 288,879 person-years (PY) of exposure and identified 15 probable NAION events – 10 among GLP-1 RA users and five among patients receiving placebo. No cases were identified among patients receiving other non-GLP-1 glucose-lowering active comparators. The incidence rate was 6.4 cases per 100,000 PY in the GLP-1 RA group and 3.8 per 100,000 PY in the comparator group. For context, the FDA cited a background incidence of 2.3–10.2 cases per 100,000 persons annually in adults older than 50.

FDA Sentinel real-world evidence study: The FDA also conducted a retrospective cohort study through its Sentinel Real-World Evidence Data Enterprise (RWE-DE) Commercial Network. It examined adults with type 2 diabetes who initiated a GLP-1 RA, a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or a dipeptidyl peptidase-4 (DPP-4) inhibitor between 2019 and 2024. Compared with DPP-4 inhibitors, GLP-1 RAs were associated with a statistically significant increase in NAION risk (hazard ratio [HR] 1.43; 95% confidence interval [CI] 1.02–2.01). The comparison with SGLT-2 inhibitors did not show a statistically significant increase (HR 1.19; 95% CI 0.91–1.54). Incidence rates ranged from 26 to 32 events per 100,000 PY across the treatment groups.

Post-marketing reports and preclinical assessment: The FDA reviewed reports submitted to its Adverse Event Monitoring System (AEMS), formerly the FDA Adverse Event Reporting System (FAERS). The agency said these reports were difficult to interpret because NAION risk factors overlap with conditions common among GLP-1 RA users, including diabetes, hypertension, sleep apnoea and kidney disease. Its review of available animal data did not identify a mechanism explaining how GLP-1 RA use might increase NAION risk.

The FDA also reviewed published observational studies. It reported that methodologically rigorous studies consistently found an increased risk among patients with type 2 diabetes initiating GLP-1 RAs compared with those initiating DPP-4 or SGLT-2 inhibitors. The agency concluded that the totality of the evidence indicated a potential increased risk and justified the class-wide labelling change.

Clinical recommendations for healthcare professionals

NAION involves reduced blood flow to the optic disc, the front part of the optic nerve. It can cause sudden, painless vision loss in one eye and may result in permanent visual impairment. The FDA advises healthcare professionals to inform patients about the potential risk and symptoms requiring prompt medical attention.

Symptoms include sudden, painless loss or reduction of vision in one eye, sometimes noticed upon waking; blurred or missing portions of vision, including blind spots or tunnel vision; distorted colour perception; and reduced central visual sharpness, such as blurry or hazy areas. Patients should contact a healthcare professional immediately if these symptoms occur.

If NAION is suspected, healthcare professionals should promptly refer the patient to an ophthalmologist for evaluation. The FDA advises clinicians to consider discontinuing GLP-1 RA treatment in patients who develop NAION, unless the benefits of continued treatment clearly outweigh the risk. Patients with a history of NAION are also at increased risk of recurrence, including in the other eye.