FDA requires a rare vision-loss warning on Ozempic and all GLP-1 drugs

The Food and Drug Administration on Monday required the makers of every GLP-1 drug, including Novo Nordisk's Ozempic and Wegovy and Eli Lilly's Mounjaro and Zepbound, to warn patients and doctors that the medicines may raise the risk of a rare eye condition that can cause permanent vision loss.

The warning lands on the most widely used drugs for type 2 diabetes and weight loss. The condition, non-arteritic anterior ischemic optic neuropathy, or NAION, can cause sudden, painless loss of vision in one eye, the agency said in a Drug Safety Communication. Drugmakers must add the risk to the Warnings and Precautions section of their labels, and the requirement covers the whole class rather than a single product.

The class now reaches well beyond diabetes and obesity. Some GLP-1 drugs are also approved to reduce the risk of heart attack and stroke in adults with heart disease, to slow kidney disease in adults with type 2 diabetes, to treat liver scarring caused by metabolic dysfunction-associated steatohepatitis and to treat moderate to severe obstructive sleep apnea in adults with obesity. The FDA said NAION cases have been reported for all currently marketed GLP-1 products.

The agency's case rests mainly on its own meta-analysis of 126 randomized clinical trials across GLP-1 development programs, which it ran because individual trials recorded few or no cases. Those trials covered 134,253 patients, 78,217 of them taking a GLP-1 drug and 56,036 taking a comparator. Reviewers identified 15 probable NAION events: 10 among GLP-1 users and five among patients on placebo. That works out to 6.4 cases per 100,000 person-years on the drugs, against 3.8 for patients given a placebo or a different glucose-lowering medicine.

The absolute risk remains small. Published studies put the rate of NAION in the general population at 2.3 to 10.2 cases per 100,000 people a year among adults older than 50, the FDA said. Known risk factors include smoking, diabetes, high blood pressure, sleep apnea, anemia and kidney disease, several of which are common among people prescribed GLP-1 drugs.

That overlap made the evidence hard to read. The FDA said reports submitted to its adverse event system were challenging to interpret because the risk factors for NAION often match the conditions GLP-1 patients already have, so it turned to other data. Its review of animal studies did not identify a mechanism by which the drugs could raise the risk.

A separate FDA study in its Sentinel real-world data network gave a mixed picture. It followed adults with type 2 diabetes who started a GLP-1 drug, an SGLT-2 inhibitor or a DPP-4 inhibitor between 2019 and 2024. It found no statistically significant increase in risk for GLP-1 drugs compared with SGLT-2 inhibitors, but did find a higher risk compared with DPP-4 inhibitors. Published observational studies that the agency described as methodologically rigorous consistently reported higher risk for GLP-1 users against both comparison groups, which the FDA said was generally consistent with its trial analysis.

The review began after a July 2024 study in JAMA Ophthalmology linked semaglutide, the active ingredient in Ozempic and Wegovy, to the condition. The FDA said it found several limitations in that study but decided the potential risk warranted further assessment. Regulators in Europe moved first. The European Medicines Agency classified NAION last year as a very rare side effect of semaglutide, affecting up to one in 10,000 patients, Euronews reported.

For patients, the FDA listed the symptoms to watch for: sudden, painless vision loss in one eye that may be noticed on waking, blind spots or tunnel vision, faded colors and blurry or hazy patches. Anyone with those symptoms should contact a health care professional right away. Patients who have had NAION should discuss whether to keep taking their GLP-1 drug, and the agency noted that an event in one eye raises the risk of one in the other.

Doctors should tell patients to report sudden vision changes, refer suspected cases promptly to an ophthalmologist and consider stopping the GLP-1 drug unless the benefits of treatment clearly outweigh the risk.

The label change arrived on the same day Eli Lilly reported late-stage sleep apnea results for orforglipron, its daily GLP-1 pill sold as Foundayo, at the American Heart Association's Scientific Sessions. Lilly plans to submit those results to the FDA by the end of the year, 1NFLUENC3 reported.