FDA orders vision-loss warnings across GLP-1 drug class

MARYLAND: Millions of people worldwide use glucagon-like peptide-1 (GLP-1) medicines to manage type 2 diabetes and obesity, but a potential risk of a serious eye condition has prompted the US Food and Drug Administration (FDA) to require new safety warnings across the entire drug class.

On November 9, the FDA announced that manufacturers of all medicines with GLP-1 receptor agonist (GLP-1 RA) activity must add information about the potential increased risk of non-arteritic anterior ischemic optic neuropathy (NAION) to the Warnings and Precautions section of their product labelling.

The requirement covers popular medicines including Novo Nordisk's Ozempic, Wegovy and Rybelsus, as well as Eli Lilly's Mounjaro and Zepbound. It also extends to other GLP-1 medicines, including those containing liraglutide, dulaglutide, lixisenatide, exenatide and orforglipron.

NAION is a rare condition involving reduced blood flow to the front part of the optic nerve. It can cause sudden, painless vision loss, usually in one eye, and may result in permanent visual impairment.

The FDA said its decision followed a comprehensive review of clinical trial data, animal research, post-marketing safety reports, observational studies and individual case reports.

Importantly, the warning identifies a potential increased risk rather than establishing that GLP-1 medicines directly cause the condition.

FDA warning covers the entire GLP-1 drug class

Although Ozempic and Zepbound have received considerable attention following the announcement, the regulatory requirement is not restricted to these widely used diabetes and weight-management medicines.

The FDA's list of affected products includes:

• Semaglutide: Ozempic, Wegovy and Rybelsus.
• Tirzepatide: Mounjaro and Zepbound.
• Liraglutide: Victoza and Saxenda.
• Dulaglutide: Trulicity.
• Exenatide: Generic exenatide products.
• Lixisenatide: Used in combination with insulin glargine in Soliqua.
• Liraglutide and insulin degludec: Combined in Xultophy.
• Orforglipron: Foundayo, an oral GLP-1 receptor agonist.

The FDA also lists Byetta, an exenatide brand, but notes that its application was voluntarily withdrawn in 2025 for reasons unrelated to safety or effectiveness. Generic exenatide products remain marketed.

One important distinction is that tirzepatide, the active ingredient in Mounjaro and Zepbound, acts on both GIP and GLP-1 receptors. It is therefore a dual GIP/GLP-1 receptor agonist, but falls within the FDA's warning requirement because it also has GLP-1 receptor activity.

Similarly, orforglipron is an oral small-molecule GLP-1 receptor agonist, rather than a peptide-based medicine.

The FDA said NAION cases have been reported across all currently marketed GLP-1 RA products, supporting its decision to extend the labelling requirement across the class.

What is NAION and why is it a serious concern?

Non-arteritic anterior ischemic optic neuropathy is an eye condition that develops when blood supply to the optic nerve head, where the optic nerve connects to the back of the eye, is reduced.

The optic nerve carries visual information from the eye to the brain. When its blood supply is compromised, the resulting damage can affect vision and, in some cases, cause permanent visual impairment.

The condition typically presents with sudden, painless vision loss in one eye. Some patients first notice the problem when they wake up.

According to the FDA, warning signs include:

• Sudden, painless reduction or loss of vision in one eye.
• Blurred vision or missing portions of the visual field.
• Blind spots or tunnel vision.
• Distorted colour perception.
• Reduced central visual sharpness, including blurry or hazy areas.

NAION is particularly concerning because there is currently no proven treatment that reliably reverses the resulting optic nerve damage.

The FDA identifies several potential risk factors, including diabetes, smoking, high blood pressure, sleep apnoea, anaemia and kidney disease.

Patients who have already experienced NAION in one eye also face an increased risk of developing the condition in the other eye.

The regulator advises patients experiencing sudden visual changes or other symptoms associated with NAION to contact a healthcare professional immediately.

What did the FDA's safety review reveal?

The FDA's decision followed an extensive assessment of available evidence, including clinical trials, real-world patient data and reports submitted through its adverse-event monitoring system.

A key component was a meta-analysis of 126 randomised controlled clinical trials involving 134,253 participants, including 78,217 people who received GLP-1 medicines and 56,036 who received comparator treatments.

Across 288,879 person-years of exposure, researchers identified 15 probable NAION cases: 10 among GLP-1 users and five among patients receiving placebo. No cases were identified among participants receiving other non-GLP-1 glucose-lowering medicines in this analysis.

The resulting incidence rate was 6.4 NAION cases per 100,000 person-years among GLP-1 users, compared with 3.8 per 100,000 person-years among comparator groups.

A person-year represents one person followed for one year, making this measure useful for comparing event rates across groups with different follow-up periods.

The FDA also examined real-world data through its Sentinel Real-World Evidence Data Enterprise, assessing adults with type 2 diabetes who started GLP-1 medicines or other diabetes treatments between 2019 and 2024.

The analysis compared GLP-1 users with patients receiving two other classes of diabetes medicines: sodium-glucose cotransporter-2 (SGLT-2) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors.

NAION incidence rates ranged from 26 to 32 cases per 100,000 person-years across the treatment groups.

The rates were 30–32 cases among GLP-1 users, 31 among SGLT-2 inhibitor users and 26 among DPP-4 inhibitor users.

Importantly, the FDA found no statistically significant increase in NAION risk among GLP-1 users compared with SGLT-2 inhibitor users. However, the comparison with DPP-4 inhibitors showed a statistically significant increase.

The estimated hazard ratio was 1.19 for GLP-1 medicines compared with SGLT-2 inhibitors, with a 95% confidence interval of 0.91–1.54. Against DPP-4 inhibitors, the hazard ratio was 1.43, with a 95% confidence interval of 1.02–2.01.

The agency also reviewed published observational studies, which generally reported an increased risk among patients with type 2 diabetes initiating GLP-1 medicines compared with those starting DPP-4 or SGLT-2 inhibitors.

However, its review of available animal data did not identify a mechanism explaining how GLP-1 medicines might increase NAION risk.

Research has strengthened concerns, but causation remains uncertain
The possible association between GLP-1 medicines and NAION has attracted increasing scientific attention since 2024.

The FDA said its investigation followed a July 2024 study published in JAMA Ophthalmology, titled Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide.

The study reported an association between semaglutide use and NAION, prompting the agency to examine the potential risk more extensively. Although the FDA identified limitations in the initial research, it considered the findings sufficient to warrant further investigation.

Further evidence emerged in March 2025 when a large retrospective cohort study published in JAMA Ophthalmology examined nearly 175,000 patients with diabetes receiving semaglutide and an equal number receiving non-GLP-1 medicines.

Led by Alan Y. Hsu, MD, and colleagues, the study found no statistically significant increase in NAION risk during the first year of treatment. However, after two years, the semaglutide group had 39 reported cases compared with 18 in the comparison group, with an estimated hazard ratio of 2.39.

The researchers reported an association between longer-term semaglutide use and increased NAION risk, but acknowledged that the retrospective design could not establish a cause-and-effect relationship.

These findings add to the evidence supporting further investigation, but they do not establish that semaglutide or other GLP-1 medicines directly cause the condition.

The distinction is important because patients receiving these medicines frequently have underlying conditions, particularly diabetes and high blood pressure, that are themselves associated with NAION risk.

European regulator had already flagged semaglutide-related eye risk

The FDA's announcement follows an earlier regulatory assessment in Europe.

In June 2025, the European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) concluded that NAION was a very rare side effect of semaglutide-containing medicines, including Ozempic, Wegovy and Rybelsus.

The European regulator classified the condition as very rare, meaning it could affect up to one in 10,000 people taking semaglutide.

Its assessment of several large epidemiological studies suggested an approximately two-fold increase in NAION risk among adults with type 2 diabetes taking semaglutide compared with those not receiving the medicine.

The EMA estimated this could represent approximately one additional NAION case per 10,000 person-years of semaglutide treatment.

It recommended updating the product information for semaglutide medicines and advised that treatment should be discontinued if NAION is confirmed.

The FDA's November 2026 action is broader in scope because it extends the additional warning requirement to all medicines with GLP-1 receptor activity, rather than focusing specifically on semaglutide.

Novo Nordisk and Eli Lilly respond to the warning

The two pharmaceutical companies behind several of the world's most widely used GLP-1 medicines have responded to the FDA's announcement.

An Eli Lilly spokesperson said the FDA's drug safety communication applied to all medicines with GLP-1 receptor agonist activity and did not refer to findings specific to the company's medicines.

The spokesperson said the company was carefully evaluating the update and would respond to the FDA.

A Novo Nordisk spokesperson maintained that the available data did not establish a cause-and-effect relationship between its medicines and NAION, adding that the company remained confident in the benefit-risk profile of its GLP-1 treatments.

Citi analyst Geoff Meacham said the FDA's action could temporarily increase patient and investor concern but expected the rarity of NAION and the substantial health benefits of GLP-1 medicines to preserve their overall favourable benefit-risk profile.

These benefits include improvements in weight management and blood glucose control, while certain medicines in the class also have approved indications for reducing cardiovascular risks, protecting kidney health, treating obstructive sleep apnoea and managing metabolic dysfunction-associated steatohepatitis.

Not all these additional indications apply to every medicine in the class.

What patients taking GLP-1 medicines should know

The FDA's announcement does not mean that patients taking Ozempic, Wegovy, Mounjaro, Zepbound or other GLP-1 medicines should automatically discontinue their treatment.

Instead, the agency is advising patients and healthcare professionals to remain alert to possible symptoms and seek prompt medical assessment if visual changes occur.

Patients should contact a healthcare professional immediately if they experience sudden, painless vision loss, blurred vision, blind spots, tunnel vision or other visual disturbances in one eye.

Healthcare professionals are advised to arrange prompt referral to an ophthalmologist if NAION is suspected.

The FDA also recommends considering discontinuation of a GLP-1 medicine in patients who develop NAION, unless the benefits of treatment clearly outweigh the risks.

Patients who have experienced a NAION event should discuss whether to continue or stop their medication with their healthcare professional rather than making treatment decisions independently.

The warning highlights the importance of continued safety monitoring as GLP-1 medicines become increasingly used for diabetes, obesity and other approved health conditions.

For patients and prescribers, the key message is not to overlook the potential eye risk or disregard the established benefits of treatment, but to recognise warning symptoms early and make informed decisions with appropriate medical guidance.

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