On Nov. 9, the U.S. Food and Drug Administration (FDA) required makers of glucagon-like peptide-1 receptor agonist drugs to flag a possible risk of non-arteritic anterior ischemic optic neuropathy (NAION), after analyses differed by comparator.
These GLP-1 receptor agonists (GLP-1 RAs) will carry the information in their labels’ Warnings and Precautions section. NAION involves reduced blood flow near the front of the optic nerve and can rapidly impair sight in one eye without pain; the loss may persist.
The FDA’s review of 126 randomized trials covered 134,253 patients and 288,879 person-years of exposure. It identified 15 probable cases: 10 among GLP-1 RA users, five among people given a placebo and none among patients taking other non-GLP-1 glucose-lowering drugs. The reported rates were 6.4 cases per 100,000 person-years for GLP-1 RA users and 3.8 cases per 100,000 person-years among comparator-treated patients.
A separate study followed adults with type 2 diabetes who started treatment from 2019 to 2024. Rates ranged from 26 to 32 cases per 100,000 person-years. The FDA found no statistically significant increase for GLP-1 RAs compared with sodium-glucose cotransporter-2 (SGLT-2) inhibitors, while its comparison with dipeptidyl peptidase-4 (DPP-4) inhibitors showed a higher risk.
The agency describes the association as a potential risk; its notice does not establish that the medicines cause NAION. It reports class-wide findings without assigning a separate risk estimate to each brand. The FDA’s list includes Ozempic, Wegovy and Rybelsus (semaglutide); Mounjaro and Zepbound (tirzepatide); Victoza and Saxenda (liraglutide); Trulicity (dulaglutide); and Foundayo (orforglipron), among other medicines.
Possible signs include abrupt vision loss without pain, blind spots or a narrowing field of view, changes in color perception and reduced central detail. The FDA says patients with symptoms should contact a health professional right away. The FDA recommends prompt referral to an ophthalmologist when NAION is suspected and says clinicians should consider stopping the GLP-1 medicine if NAION develops, unless treatment benefits clearly outweigh the risk.
In June 2025, the European Medicines Agency’s safety committee recommended listing NAION as a very rare side effect of semaglutide medicines, affecting up to one in 10,000 people, and advised stopping semaglutide if the condition is confirmed. That recommendation addressed semaglutide, while the FDA’s requirement covers the broader GLP-1 RA class. EconoTimes previously reported on the FDA’s GLP-1 label action.
