GLP-1 vision loss debate resurfaces as lawsuits mount

US patients allege optic neuropathy after treatment…FDA investigates potential link

EMA lists NAION as “very rare” adverse effect, while 1.21-million-patient study finds no increased risk

Concerns over optic neuropathy associated with GLP-1 therapies are resurfacing in the US.

Patients who developed non-arteritic anterior ischemic optic neuropathy (NAION) after using GLP-1 therapies, including Wegovy (semaglutide) and the diabetes treatment Ozempic, which contains the same active ingredient, have filed lawsuits alleging that the drugs caused their condition and subsequent vision loss.

Evidence on the association between semaglutide and NAION, however, remains conflicting. The European Medicines Agency (EMA) last year classified NAION as a “very rare adverse effect” of semaglutide, while a retrospective cohort study involving more than 1.2 million patients found no increased risk.

The US Food and Drug Administration (FDA) is also investigating a potential association, bringing renewed attention to the ocular safety of GLP-1 therapies.

Vision loss alleged after GLP-1 treatment

According to industry sources on the 21st, US patients who used GLP-1 therapies have filed lawsuits against Novo Nordisk and Eli Lilly, alleging that they developed NAION and suffered vision loss after treatment.

NAION occurs when blood flow to the optic nerve is suddenly reduced, resulting in damage to the nerve. It can cause sudden visual field defects or loss of vision, and the resulting impairment may not fully recover.

However, the drugs involved in the lawsuits cannot be interpreted as carrying the same level of evidence regarding this potential safety risk.

The FDA is investigating a potential association between GLP-1 therapies and NAION. To date, semaglutide is the only active ingredient for which a regulatory authority has formally recognized NAION as an adverse effect. Wegovy and Ozempic contain semaglutide, whereas Zepbound contains tirzepatide and differs in its mechanism of action.

Novo Nordisk and Lilly maintain that a causal relationship between their therapies and NAION has not been established. They note that differences in study populations, comparator groups and follow-up methods may contribute to the varying findings across studies.

EMA recognizes adverse effect…review also underway in Korea

Image source: Clipart Korea

The potential association between semaglutide and NAION began drawing significant safety attention in 2024.

Following observational studies reporting a higher incidence of NAION among semaglutide users, regulatory authorities began reviewing the available evidence.

After reviewing nonclinical and clinical data, post-marketing safety reports and epidemiological studies in June last year, the EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) concluded that the evidence was sufficient to support a causal association between semaglutide and NAION.

The committee subsequently recommended adding NAION as an adverse reaction to the product information for semaglutide-containing medicines, including Wegovy, Ozempic and Rybelsus.

The frequency was classified as very rare, affecting up to 1 in 10,000 people. Some large epidemiological studies reviewed by the EMA found that adults with type 2 diabetes exposed to semaglutide had approximately twice the risk of developing NAION compared with those not exposed to the drug.

In absolute terms, this corresponded to approximately one additional case of NAION per 10,000 patients treated with semaglutide for 1 year. Clinical trial data also showed a slight increase in incidence compared with placebo.

The EMA recommended that patients promptly contact a healthcare professional if they experience sudden loss of vision or rapidly worsening eyesight while receiving semaglutide and that treatment be discontinued if NAION is confirmed.

Related safety measures are also under review in Korea.

The Ministry of Food and Drug Safety said last month that it is monitoring domestic and international adverse-event reports and considering whether to add information on NAION to the labeling of semaglutide products.

No increased risk in 1.21 million patients…evidence remains mixed

However, large-scale evidence that does not support an association between semaglutide and NAION also exists.

A retrospective cohort study published last year in the international journal Military Medicine found no increased risk of NAION associated with semaglutide use.

The study analyzed 1,212,775 adults treated within the US Military Health System between December 2017 and September 2023.

The cohort included approximately 970,000 patients with type 2 diabetes and 240,000 patients with overweight or obesity, with 2,447 cases of NAION identified overall.

After adjustment for comorbidities, patients with type 2 diabetes who were prescribed semaglutide had a 64% lower risk of developing NAION than those treated with non-GLP-1 medications.

No statistically significant association between semaglutide use and NAION was identified among overweight or obese patients. Based on these findings, the researchers concluded that concerns over NAION alone did not warrant ruling out semaglutide as a treatment option.

The findings contrast with earlier observational studies that reported an increased risk.

Determining causality is further complicated by the fact that NAION itself is associated with conditions common among patients treated with semaglutide, including diabetes, obesity, hypertension and sleep apnea.

As a result, findings from observational studies may depend in part on how effectively the impact of semaglutide exposure can be separated from patients’ underlying risk factors.

Gap between regulatory assessment and clinical evidence…attention rises on FDA review

Taken together, the available evidence has generated a regulatory safety signal for a potential association between semaglutide and NAION, but studies continue to differ on the magnitude of the risk.

The EMA has formally classified NAION as an adverse effect of semaglutide after reviewing multiple sources of evidence. At the same time, data showing no increased risk, including the study of more than 1.2 million patients, continue to accumulate.

In the US in particular, the regulatory assessment remains ongoing.

The FDA is reviewing a potential association between NAION and GLP-1 therapies, including semaglutide, but has not yet required a specific NAION warning comparable to that adopted in Europe.

With related lawsuits now mounting in the US, attention is expected to focus on the FDA’s safety assessment and whether it ultimately requires changes to product labeling.

Given the low absolute incidence of NAION and the inconsistent findings across studies, however, the available evidence does not support treating the risk of optic neuropathy as uniform across the entire GLP-1 class.

An industry official said, “NAION occurs very rarely, so it would be difficult to draw definitive conclusions about the safety of semaglutide from any single study or, conversely, to recommend across-the-board discontinuation of treatment. Given the conflicting findings to date, treatment decisions should take into account each patient’s individual risk factors, including diabetes, hypertension and sleep apnea.”