FDA Slaps New Safety Warning on GLP-1 Drugs

 The FDA is requiring manufacturers of all GLP-1 drugs to update their prescribing information to include a warning about the potential risk of non-arteritic anterior ischemic optic neuropathy (NAION), a rare but potentially blinding eye condition.

Cases of NAION have been documented across all currently marketed GLP-1 products, according to the agency.

Healthcare providers should "instruct patients to immediately report sudden onset of acute, painless, decreased vision; visual field deficits; or other visual disturbances in one eye," the FDA stated in a safety communication on Monday. "If NAION is suspected, promptly refer the patient to an ophthalmologist for evaluation. Consider discontinuing the GLP-1 [receptor agonist] in patients who develop NAION, unless the benefits of treatment clearly outweigh the risk."

NAION occurs when blood flow to the optic disc is reduced. Beyond the painless vision loss -- often noticed upon waking -- symptoms can include blurred or missing visual fields, color distortion, and reduced central visual acuity. Its exact triggering mechanism remains poorly understood and animal data on GLP-1 drugs did not further elucidate a potential mechanism for the higher risk observed with the drugs, the FDA said.

The agency's action follows a wave of studies suggesting a potential link between GLP-1 drugs and NAION, including a 2024 study in JAMA Ophthalmology involving semaglutide (Ozempic, Wegovy) that FDA said prompted its review. Europe's drug regulator warned about the risk 17 months ago.

In a meta-analysis of randomized trials performed by the FDA, the agency identified 15 probable NAION events among more than 134,000 patients. Of those, 10 cases occurred among the roughly 78,000 treated with GLP-1 drugs, none were in those randomized to other glucose-lowering medications, and five occurred in placebo recipients. Incidence was 6.4 cases per 100,000 person-years among the GLP-1 drug recipients compared with 3.8 cases per 100,000 person-years among patients receiving a non-GLP-1 medication or placebo.

A retrospective cohort study performed by the FDA involving type 2 diabetes patients showed no significantly increased risk for NAION with GLP-1 agonists versus SGLT2 inhibitors (HR 1.19, 95% CI 0.91-1.54) but an increased risk was seen compared with DPP-4 inhibitors (HR 1.43, 95% CI 1.02-2.01).

Common risk factors for NAION include smoking, diabetes, hypertension, obstructive sleep apnea, anemia, and chronic kidney disease. Patients with a history of NAION carry an increased risk for recurrence.

Patients and clinicians can report suspected adverse reactions associated with GLP-1 medications to the FDA's MedWatch reporting program.

https://www.medpagetoday.com/ophthalmology/generalophthalmology/123783