The US Food and Drug Administration (FDA) is requiring new safety warnings for all glucagon-like peptide-1 receptor agonists (GLP-1 RAs) following evidence of a potential increased risk of nonarteritic anterior ischemic optic neuropathy (NAION), a rare condition that can cause sudden, painless, and potentially permanent vision loss.
In a November 9 Drug Safety Communication, the agency directed manufacturers to add NAION risk information to the Warnings and Precautions section of prescribing information. The requirement covers medications used for type 2 diabetes and weight management, including semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Victoza, Saxenda), and tirzepatide (Mounjaro, Zepbound).
The decision followed a review of clinical trials, observational studies, postmarketing reports, and animal data. In a meta-analysis of 126 randomized controlled trials involving 134,253 patients, the agency identified 15 probable NAION cases: 10 among 78,217 GLP-1 RA recipients and 5 among 56,036 comparator recipients, with all 5 cases occurring in the placebo group. NAION incidence was 6.4 cases per 100,000 person-years with GLP-1 RAs vs 3.8 per 100,000 person-years with comparators.
The FDA also conducted a retrospective cohort study using its Sentinel real-world evidence database, comparing adults with type 2 diabetes who initiated GLP-1 RAs, sodium-glucose cotransporter-2 (SGLT2) inhibitors, or dipeptidyl peptidase-4 (DPP4) inhibitors between 2019 and 2024. NAION incidence ranged from 30 to 32 cases per 100,000 person-years with GLP-1 RAs, vs 31 for SGLT2 inhibitors and 26 for DPP4 inhibitors. There was a statistically significant increase in NAION risk compared with DPP4 inhibitors, but not with SGLT2 inhibitors.
The agency cautioned that interpreting postmarketing reports was difficult because NAION risk factors, including diabetes, hypertension, and sleep apnea, overlap with conditions common among GLP-1 RA users. NAION cases have been reported with all currently marketed GLP-1 RAs. However, the agency's animal data review did not identify a mechanism explaining the potential increased risk.
The announcement advises health care professionals to instruct patients to immediately report sudden, painless visual changes and to promptly refer suspected NAION cases for ophthalmologic evaluation. The agency also recommends considering GLP-1 RA discontinuation in patients who develop NAION unless treatment benefits clearly outweigh the risks.
Sources:FDA
