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FDA requires NAION warning across the GLP-1 receptor agonist class

Optometry 360

By Mario Nacinovich

The US Food and Drug Administration (FDA) is requiring every application holder for a glucagon-like peptide-1 receptor agonist (GLP-1 RA) to add language to the Warnings and Precautions section of labeling describing a potential increased risk of non-arteritic anterior ischemic optic neuropathy (NAION), according to a Drug Safety Communication issued November 9, 2026.

The requirement applies class-wide. It covers semaglutide (Ozempic, Rybelsus, Wegovy), tirzepatide (Mounjaro, Zepbound), liraglutide, dulaglutide, exenatide, 2 insulin combination products, and the recently approved orforglipron (Foundayo). The FDA noted that NAION cases have been reported for all currently marketed GLP-1 RA products.

For optometrists, the action formalizes a question that has followed the class since 2024, when Hathaway and colleagues reported an association between semaglutide and NAION in JAMA Ophthalmology. The FDA identified several limitations in that study but concluded that further assessment was warranted, and it then reviewed clinical trial, animal, and postmarketing data.

What the Evidence Shows

The agency’s central analysis is a meta-analysis of 126 randomized, controlled trials across GLP-1 RA development programs, encompassing 134,253 patients and 288,879 person-years (PY) of exposure. Reviewers identified 15 probable NAION events: 10 among patients treated with GLP-1 RAs and 5 among patients who received placebo, translating to 6.4 events per 100,000 PY with GLP-1 RAs versus 3.8 per 100,000 PY with comparators.

A retrospective cohort study in the FDA’s Sentinel real-world evidence network examined adults with type 2 diabetes who started a GLP-1 RA, a sodium glucose co-transporter-2 (SGLT-2) inhibitor, or a dipeptidyl peptidase-4 (DPP-4) inhibitor between 2019 and 2024. Incidence ranged from 26 to 32 events per 100,000 PY across the groups. The risk with GLP-1 RAs was not significantly higher than with SGLT-2 inhibitors (hazard ratio [HR], 1.19; 95% CI, 0.91-1.54), but it was higher than with DPP-4 inhibitors (HR, 1.43; 95% CI, 1.02-2.01).

According to the agency, methodologically rigorous published observational studies consistently reported increased NAION risk among patients with type 2 diabetes who initiated GLP-1 RAs compared with those who initiated either of the other 2 drug classes.

What Remains Uncertain

The FDA characterizes the risk as potential, and the event counts are small: 15 probable cases in nearly 289,000 PY. The absolute difference in the pooled trial data is roughly 2.6 events per 100,000 PY, and the rates in both arms fall within the published background incidence of 2.3 to 10.2 cases per 100,000 persons per year among adults older than 50 years.

The agency’s review of animal data did not identify a mechanism by which GLP-1 RAs could increase NAION risk. Adverse event reports were difficult to interpret because NAION risk factors, including diabetes, hypertension, sleep apnea, and kidney disease, overlap with the conditions for which these agents are prescribed.

Clinical Implications

The FDA advises healthcare professionals to instruct patients to report immediately any sudden, painless decrease in vision, visual field deficit, or other visual disturbance in one eye. When NAION is suspected, the guidance is to refer promptly to an optometrist. Prescribers are told to consider discontinuing the GLP-1 RA in patients who develop NAION unless the benefits of treatment clearly outweigh the risk.

Two points bear directly on eye care practice. Patients with a history of NAION are at increased risk of recurrence, and an event in 1 eye raises the risk in the fellow eye. Decisions about continuing therapy will therefore benefit from coordination among the optometrist, the prescriber, and the patient, particularly because several agents carry cardiovascular and kidney indications.

Patients are advised to contact a healthcare professional right away if symptoms occur. The communication does not tell patients to stop treatment on their own; it directs those who have had a NAION event to discuss continuation with their clinician.

Optometrists can expect more questions from patients and referring clinicians. The labeling change gives those conversations a common reference point: a rare event, a potential association, and a clear pathway for evaluation.

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