FDA is requiring manufacturers of all glucagon-like peptide-1 receptor agonist (GLP-1 RA) medications to update the warnings and precautions section of their labeling describing a potential increased risk of non-arteritic anterior ischemic optic neuropathy (NAION).

NAION is a rare condition that can cause acute, painless, decreased vision in one eye, including permanent vision loss.¹ The requirement touches a drug class with broad reach across both diabetes and obesity care, with GLP-1 RAs mimicking the effects of GLP-1, released by the intestine that lowers blood glucose after eating and acts on parts of the brain that control appetite and food intake.

The class is widely used to treat type 2 diabetes and maintain reduced body weight, with several individual medications in the class carrying additional approved uses such as;

Reducing the risk of major cardiovascular events including death, heart attack, or stroke in adults with known heart disease and either obesity/overweight or type 2 diabetes.

Treating metabolic dysfunction-associated steatohepatitis with moderate-to-advanced liver fibrosis.¹

Lowering the risk of worsening kidney disease, kidney failure, and cardiovascular death in adults with type 2 diabetes and chronic kidney disease.

Treating moderate to severe obstructive sleep apnea in adults with obesity.

What GLP-1’s are affected?

The agency is requiring application holders for every approved GLP-1 RA to update labeling with the new warning, including approved treatments such as, exenatide, liraglutide, dulaglutide, lixisenatide and liraglutide combinations with insulin, semaglutide, tirzepatide, and most recently orforglipron.¹

According to a report from NBC News, spokespeople for both Eli Lilly and Novo, are saying patient safety is “top priority.”²

What is NAION and what should patients watch for?

NAION is caused by decreased blood flow to the front part of the optic nerve, known as the optic disc, though its underlying cause is not completely understood.¹ Risk factors may include smoking, diabetes, high blood pressure, sleep apnea, anemia, and kidney disease, with patients who have experienced NAION in one eye facing an increased risk of it occurring in the other.¹

As GLP-1 use has expanded rapidly across both diabetes and obesity care, questions about how well patients understand the full risk profile of the drug class have followed just as quickly. Mark Bagnall, CEO of Phenomix, told Pharmaceutical Executive earlier this year that “those of us who are in the business owe it to patients to let them be fully aware that these risks exist.”

FDA is advising patients and caregivers to contact a health care professional immediately if any of these symptoms occur. For patients who have already had a NAION event, FDA is recommending a discuss with their health care professional whether to continue or stop their GLP-1 RA.¹

What evidence led FDA to this conclusion?

FDA’s review was prompted in part by a July 2024 article titled “Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide.” examining the risk of NAION in patients prescribed semaglutide.¹ While the agency identified limitations in that study, it determined further assessment was warranted and undertook a comprehensive evaluation of clinical trial data, animal data, and postmarketing data, including observational studies and case reports, along with a review of adverse event reports submitted through FDA’s Adverse Event Monitoring System.¹

A review of available animal data did not identify a mechanism by which GLP-1 RA use could increase NAION risk, so FDA then conducted a meta-analysis of 126 randomized, controlled clinical trials across GLP-1 RA development programs, covering 134,253 patients and 288,879 person-years of exposure. The analysis identified 15 probable NAION events: ten in patients treated with GLP-1 RAs, five in patients on placebo, and none in patients receiving a non-GLP-1 RA glucose-lowering medication.¹

The resulting incidence rate was 6.4 NAION cases per 100,000 person-years among GLP-1 RA users, compared with 3.8 cases per 100,000 person-years among comparator-treated patients; published literature put the background incidence of NAION in the general population at 2.3 to 10.2 cases per 100,000 persons per year in adults over 50.¹

FDA separately conducted a retrospective cohort study using its Sentinel Real-World Evidence Data Enterprise Commercial Network, examining adults with type 2 diabetes who started a GLP-1 RA, an SGLT-2 inhibitor, or a DPP-4 inhibitor between 2019 and 2024. Incidence rates in that study ranged from 26 to 32 events per 100,000 person-years. GLP-1 RA use showed no statistically significant increase in NAION risk compared with SGLT-2 inhibitors (hazard ratio 1.19, 95% confidence interval 0.91–1.54), but did show an increased risk compared with DPP-4 inhibitors (hazard ratio 1.43, 95% confidence interval 1.02–2.01).

Based on the totality of this evidence, FDA concluded there is a potential increased risk of rare NAION events associated with GLP-1 RA use and is requiring the labeling update across the class.¹

Sources

1. FDA Requires Safety Labeling Changes for Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) Due to Potential Increased Risk of Rare But Serious Eye Condition U.S. Food and Drug Association November 9, 2026, https://www.fda.gov/drugs/drug-safety-communications/fda-requires-safety-labeling-changes-glucagon-peptide-1-receptor-agonists-glp-1-ras-due-potential
2. FDA orders new warning on GLP-1s over rare eye condition linked to sudden blindness NBC News November 9, 2026, https://www.nbcnews.com/health/health-care/fda-orders-new-warning-glp-1s-rare-eye-condition-linked-sudden-blindne-rcna608309