The Food and Drug Administration on Monday ordered the makers of GLP-1 drugs, including Ozempic, Wegovy, Mounjaro and Zepbound, to warn on their labels of a possible increased risk of a rare eye condition that can cause permanent blindness in one eye.
The order covers every GLP-1 drug on the U.S. market, from generic exenatide, first approved in 2005, to Foundayo, the Eli Lilly pill approved this year, according to the agency’s drug safety communication. The condition, non-arteritic anterior ischemic optic neuropathy, or NAION, now has to appear in the warnings and precautions section of each label.
NAION starts when blood flow to the optic nerve is restricted, Beth Mole reported for Ars Technica. The nerve swells, cells die and the patient loses sight abruptly, usually without pain. Often the loss doesn’t come back.
“FDA concluded that there is a potential increased risk of rare NAION events in patients taking GLP-1 RAs,” the agency said. It also said that “NAION cases have been reported for all currently marketed GLP-1 RA products.”
The numbers behind that finding are small. In a meta-analysis of 126 clinical trials with 134,253 patients, the FDA counted 15 probable cases: 10 among people taking GLP-1 drugs, five on placebo and none on other glucose-lowering drugs. That works out to 6.4 cases per 100,000 person-years on the drugs, against 3.8 for the comparison groups.
The agency’s own Sentinel study, which tracked adults with Type 2 diabetes who started treatment from 2019 to 2024, was murkier. Patients on GLP-1 drugs developed NAION at 30 to 32 cases per 100,000 person-years, compared with 31 for patients on SGLT-2 inhibitors, a difference the FDA said was not statistically significant. Against DPP-4 inhibitors, at 26 cases, the risk was higher, with a hazard ratio of 1.43.
How the drugs might cause the condition is unknown. A review of animal data “did not identify a mechanism,” the FDA said.
Part of the difficulty is who takes the drugs. Diabetes, heart disease, high blood pressure, high cholesterol, metabolic syndrome and obstructive sleep apnea all raise the odds of NAION, and all are common among GLP-1 patients. The FDA said the overlap made reports to its adverse event database hard to interpret. The American Academy of Ophthalmology puts the condition’s rate at two to 10 people per 100,000 in the general population, and the FDA cited 2.3 to 10.2 cases per 100,000 a year in adults over 50.
The review began with a July 2024 study by Harvard researchers in JAMA Ophthalmology. It followed 710 patients with diabetes and 979 with overweight or obesity, some on semaglutide, the drug in Ozempic and Wegovy, and some on other medicines. After 36 months, 8.9 percent of the diabetes patients on semaglutide had NAION, compared with 1.8 percent of those on other drugs. In the obesity group it was 6.7 percent against 0.8 percent.
That study had limits, which the FDA acknowledged even as it decided more work was warranted. All the patients came from one referral center that handled most of the region’s NAION cases, and the rates it found were far above those in the general population, a sign of possible selection bias. It also didn’t account for how severe the patients’ diabetes was.
The FDA told doctors to send suspected cases to an ophthalmologist promptly and to consider stopping the drug in patients who develop NAION “unless the benefits of treatment clearly outweigh the risk.” Patients should call a health care provider right away if they notice sudden vision loss in one eye, often on waking, or blind spots, tunnel vision, distorted color or less sharp central vision, the agency said. A case in one eye raises the risk in the other.