The FDA is requiring an update to the labels of 12 different GLP-1 receptor agonists after a deep dive by the agency suggested the metabolic medicines may potentially increase the risk of a rare eye disease called non-arteritic anterior ischemic optic neuropathy (NAION).
Caused by a sudden reduction in blood flow to the front part of the optic nerve, NAION is marked by optic nerve swelling and sudden vision loss. The condition can lead to vision issues and even permanent blindness, often in one eye.
Novo’s obesity and diabetes franchise Wegovy and Ozempic as well as Eli Lilly’s rivals Mounjaro, Zepbound and its new oral med Foundayo are among the dozen drugs that will need to add NAION to the “warnings and precautions” section of their labels. The FDA said in its communication published Monday, Nov. 9 that NAION cases have been reported for all currently marketed GLP-1 RA products.
“Patient safety is Lilly's top priority," a Lilly spokesperson told Fierce. "FDA's drug safety communication applies to all medicines with GLP-1 RA activity and does not reference any findings specific to Lilly medicines. We are carefully evaluating the update and will respond to FDA promptly."
The agency was prompted to do an investigation after a 2025 JAMA Ophthalmology study of 175,000 patients with diabetes found that those taking semaglutide, the active ingredient in Wegovy and Ozempic, more than doubled their risk of NAION after two years on the medication.
Initially, the regulator reviewed reports of NAION among patients taking GLP-1 received through its Adverse Event Monitoring System (AEMS). Those cases, however, proved difficult to interpret because the risk factors for NAION—which smoking, diabetes, high blood pressure, sleep apnea, anemia, and kidney disease—"often overlap with conditions common in patients treated with GLP-1 RAs,” the FDA wrote.
From there, agency officials went on to comb through the available animal, clinical trial, and post marketing data as well as observational studies and case reports.
While the animal data offered no potential mechanism for how GLP-1 RA might cause NAION, a meta-analysis of 126 trials and more than 134,000 patients found 15 events that were likely caused by NAION. Ten of those events were in patients taking GLP-1 RAs, five were in patients on placebo, and zero events in patients receiving a non-GLP-1 treatment.
Overall, the incidence rate of NAION was 6.4 events per 100,000 patient years compared to 3.8 events in patients taking a placebo or alternative. Based on these data the risk of NAION is relatively higher for patients on a GLP-1 RA, but still very low for both groups.
The FDA also undertook a retrospective study using its Sentinel Real-World Evidence Data Enterprise (RWE-DE) Commercial Network. The study looked at NAION rates between 2019 and 2024 in patients with type 2 diabetes who took a GLP-1 compared to those that took older classes of medicines, namely sodium glucose co-transporter-2 (SGLT-2) inhibitor or a dipeptidyl peptidase-4 (DPP-4) inhibitor. The NAION risk with GLP-1 RA therapy was not increased compared to SGLT-2s—but it was significantly higher compared to DPP-4 inhibitors.
In August, a consensus statement from the North American Neuro-Ophthalmology Society and the American Academy of Ophthalmology noted a similar finding, that GLP-1 RAs may be associated with a roughly two-fold increase in relative risk of NAION. But even then, “the overall magnitude of the risk of NAION remains low,” the experts wrote.
Screening for NAION among patients take GLP-1 was also not recommended.
Given the rarity of NAION “and substantial weight, glycemic, cardiovascular, renal, and sleep apnea benefits” that GLP-1s deliver, Citi analysts said the weight loss treatments should “preserve a favorable benefit-risk profile.”
While the FDA’s class-wide labeling action is expected to cause a stir, the analysts noted that PDE5 inhibitor erectile-dysfunction therapies such as Pfizer's Viagra have carried NAION since 2005 without an interruption to broad adoption.