The US Food and Drug Administration (FDA) is requiring updated safety labeling for all glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications following a review identifying a potential increased risk of nonarteritic anterior ischemic optic neuropathy (NAION), a rare condition that can cause permanent vision loss.

In a November 9 safety communication, the agency reported findings from a meta-analysis of 126 randomized controlled trials involving 134,253 patients. NAION occurred at a rate of 6.4 cases per 100,000 person-years among GLP-1 RA users, compared with 3.8 cases per 100,000 person-years among patients receiving placebo or other glucose-lowering medications.

A separate FDA retrospective cohort study found no statistically significant increase in NAION risk compared with sodium-glucose cotransporter-2 inhibitors (hazard ratio [HR], 1.19; 95% CI, 0.91-1.54), but identified an increased risk compared with dipeptidyl peptidase-4 inhibitors (HR, 1.43; 95% CI, 1.02-2.01).

The FDA found no mechanism explaining the potential association. However, NAION cases have been reported with all currently marketed GLP-1 RAs, including semaglutide and tirzepatide products.

The agency advises clinicians to promptly refer patients with suspected NAION for ophthalmic evaluation and consider discontinuing GLP-1 RA treatment in these cases unless its benefits clearly outweigh the risks.