The FDA on Monday required all glucagon-like peptide-1 receptor agonist (GLP-1 RA) makers to add a warning about non-arteritic anterior ischemic optic neuropathy (NAION) to labels. The condition, also informally referred to as “eye stroke,” is a sudden, painless, often permanent vision loss in one eye, with no proven treatment. The FDA’s decision is based on a review of clinical trials, observational studies, animal data and case reports. The FDA is requiring an update to the Warnings and Precautions section of the label, not a boxed warning. It tells clinicians to have patients report sudden vision changes right away, refer suspected cases to an ophthalmologist and “consider” stopping the drug if NAION develops, unless the benefits clearly outweigh the risk.
Existing data shows mixed results
The warning is class-wide, but the evidence behind it is mixed and the absolute risk is small. The FDA’s real-world study of adults with type 2 diabetes found no statistically significant risk increase compared with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, but a 43% higher risk than with dipeptidyl peptidase-4 (DPP-4) inhibitors. An analysis of 126 trials involving 134,253 GLP-1 users and comparison patients found 15 probable NAION events, 10 of them in GLP-1 users.
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That works out to 6.4 cases per 100,000 person-years among GLP-1 users versus 3.8 among comparison patients, an observed difference of 2.6 cases per 100,000 person-years. The FDA also cites a general-population rate of 2.3 to 10.2 cases per 100,000 adults over 50 per year, but that figure comes from a different population and isn’t directly comparable to the trial rates.
Several major studies have produced conflicting findings. A study of U.S. health records in the TriNetX network that grouped users of semaglutide and tirzepatide together found 76% higher NAION risk than with other diabetes drugs. During follow-up of up to two years, researchers recorded 35 cases among 79,699 patients taking semaglutide or tirzepatide versus 19 among 79,699 comparison patients. The hazard ratio was 1.76, with a 95% confidence interval of 1.01–3.07. In contrast, a Cleveland Clinic study of about 220,000 GLP-1 users with type 2 diabetes, including about 120,000 on semaglutide, found no statistically significant increase in NAION risk.
Legal action and industry response
Drugmakers have begun responding to the labeling update. Eli Lilly told USA Today in a statement that it is “carefully evaluating the update and will respond to the FDA promptly.” Novo Nordisk spokesperson Liz Skrbkova told the paper the company does not believe the data “establish a cause-and-effect relationship.” The company has listed NAION as a very rare side effect in EU leaflets since a 2025 European Medicines Agency review. As of Oct. 1, 247 cases were pending in the federal NAION multidistrict litigation. The suits against Novo Nordisk and Eli Lilly allege failure to warn of NAION.
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Claims are moving forward in other regions as well. In November 2025, Denmark’s patient compensation body, funded by the state and insurers, awarded four claimants a combined 800,000 Danish kroner (about $124,000). The patients said they developed NAION after taking Wegovy or Ozempic. The American Optometric Association has recommended a baseline eye exam to check optic nerve health for new GLP-1 users since 2025. Companies can still contest the labeling language before the FDA finalizes it.
Review of observational studies and regulatory guidance
According to the FDA, methodologically rigorous observational studies “consistently” showed increased risk in new GLP-1 users with type 2 diabetes compared with patients starting DPP-4 or SGLT-2 inhibitors. Two Scandinavian studies involving type 2 diabetes patients on semaglutide concluded that the drug was associated with increased risk of NAION.
