Analysts Question Eye Risk Link to Novo's Ozempic, Wegovy

Researchers from Harvard University have initiated a study after observing cases of nonarteritic anterior ischemic optic neuropathy (NAION) among users of semaglutide, a GLP-1 analog. Semaglutide is the active ingredient in the diabetes and obesity medications Ozempic and Wegovy, produced by Novo Nordisk. The study, recently published in JAMA Ophthalmology, suggests a potential link between semaglutide and NAION, a vision loss disorder.

According to the study, individuals taking semaglutide are four to nearly eight times more likely to develop NAION compared to those on other non-GLP-1 medications for diabetes and weight loss. NAION is characterized by a reduced blood supply to the optic nerve, leading to vision loss. This condition is noted as the second most common form of optic nerve damage, with an annual incidence rate of 2.3 to 10.2 per 100,000 people over the age of 50 in the United States, as per the American Academy of Ophthalmology.

However, a team of analysts from Leerink Partners, led by David Risinger, has advised caution in drawing conclusions from this single study. They highlighted that the analysis shows an association rather than establishing a direct causative relationship between semaglutide and NAION. The study itself acknowledges the need for larger retrospective studies, post-marketing analyses of GLP-1s, or prospective clinical trials to confirm the findings.

The Harvard study evaluated nearly 17,000 patients examined by neuro-ophthalmologists at Massachusetts Eye and Ear from December 2017 to November 2023. Patients taking Ozempic or Wegovy were compared to non-users based on various baseline characteristics, including conditions related to NAION.

Among 710 patients with Type 2 diabetes, the incidence of NAION over 36 months was 8.9% for semaglutide users, compared to 1.8% for the non-GLP-1 cohort. In 979 overweight or obese individuals, the incidence rates were 6.7% for semaglutide users versus 0.8% for those on other non-GLP-1 treatments.

The study's authors cautioned that their findings might not be broadly applicable to other settings, as they were derived from a specialized neuro-ophthalmology service at Massachusetts Eye and Ear, which evaluates a significant portion of the Boston area's NAION cases. They suggested that a larger retrospective, multicenter population-based study, a prospectively designed randomized clinical trial, or a postmarket analysis of all GLP-1 receptor agonists would be ideal to confirm their findings. However, conducting such studies may be challenging due to the lack of a specific diagnostic code for NAION.

Currently, NAION is not listed as a side effect on the labels of Ozempic or Wegovy. The increasing use of GLP-1 medications has led to numerous population-based studies investigating their potential risks and benefits. For example, previous reports linking semaglutide to suicidal thoughts were refuted by a large study published in Nature Medicine, involving 1.8 million patients. The FDA and the European Medicines Agency also found no association between the drug and suicidal thoughts or actions.

Other research has suggested some unexpected benefits of GLP-1 medications. A recent study published in JAMA Network Open involving 1.6 million patients with Type 2 diabetes found that GLP-1 drugs significantly reduced the risk of 10 obesity-related cancers compared to insulin. However, these drugs did not decrease the risk of 13 other cancers when compared with metformin, but instead showed an increased risk of kidney cancer.

Meanwhile, both Novo Nordisk and its competitor Eli Lilly are exploring the efficacy of their GLP-1 offerings in conditions beyond diabetes and weight loss. Eli Lilly’s dual agonist, Zepbound, has shown promise in treating obese patients with obstructive sleep apnea. Novo Nordisk's semaglutide has demonstrated benefits in slowing kidney disease progression in diabetic patients with chronic kidney disease. Additionally, Wegovy received FDA approval earlier this year to reduce the risk of cardiovascular events in overweight or obese patients with cardiovascular disease.