Novo's Ozempic, Wegovy linked to potential eye problem? Not so fast, analysts say

Novo Nordisk’s massively successful GLP-1 analog semaglutide, the active ingredient in the popular diabetes and obesity meds Ozempic and Wegovy, may be linked to a vision loss disorder, a new study suggests. But one team of analysts cautioned against reading too much into the analysis.

The study found that people taking semaglutide were four to nearly eight times more likely to develop nonarteritic anterior ischemic optic neuropathy (NAION) than their peers on other non-GLP-1 meds for diabetes and weight loss. The study was conducted by researchers at Harvard University and published last week in JAMA Ophthalmology.

NAION is an eye condition that’s marked by decreased blood supply to the optic nerve, causing vision loss. It’s the second most common form of optic nerve damage, with an annual incidence rate estimated at around 2.3 to 10.2 per 100,000 among people over 50 years of age in the U.S., according to the American Academy of Ophthalmology.

The study raises questions, but a Leerink Partners team led by David Risinger said in a Thursday note that they “do not expect this single analysis to impact prescribing trends” of Ozempic and Wegovy. That’s because, as the study authors themselves noted, the analysis was designed to report an “association” but not to establish a causal relationship.

“Larger retrospective studies, post-marketing analyses of GLP-1s, and/or prospective clinical trials would be required to confirm the findings,” the analysts wrote.

The Harvard researchers launched the study after noticing cases of NAION among semaglutide takers in clinical practice. So they evaluated nearly 17,000 patients seen by neuro-ophthalmologists at Massachusetts Eye and Ear between December 2017 and November 2023. Patients who were taking either Ozempic or Wegovy were matched with non-takers by various baseline characteristics, including comorbidities related to NAION.

Among 710 patients with Type 2 diabetes, the cumulative NAION incidence over a 36-month period was 8.9% for users of semaglutide compared with 1.8% in the non-GLP-1 cohort.

Among 979 individuals who were overweight or obese, the 36-month rates were 6.7% and 0.8% for the users of Novo’s med and other non-GLP-1 treatments, respectively.

As the authors noted, Massachusetts Eye and Ear clinic includes a specialized neuro-ophthalmology service that evaluates a large proportion of the Boston area’s NAION cases. “[T]herefore, our findings may not be fully generalizable to other settings,” they wrote in the study.

The best approaches to confirm the findings, the researchers noted, would be to conduct a much larger retrospective, multicenter population-based study, a prospectively designed randomized clinical trial or a postmarket analysis of all GLP-1 receptor agonists. But large studies may be difficult to run, because there isn’t a specific diagnostic code for NAION, the authors said. For this study, the researchers manually reviewed records and found that 40% of cases marked as ischemic optic neuropathy, the closest code relevant to NAION, were actually not NAION.

NAION is currently not listed as a side effect in the labels of Ozempic or Wegovy.

The increasing use of GLP-1 meds has spurred multiple population-based studies exploring their potential risks and benefits. Previous anecdotal reports of suicidal thoughts related to the use of semaglutide were recently refuted by a large Nature Medicine study involving 1.8 million patients. The FDA and the European Medicines Agency later found no association between the Novo drug and suicidal thoughts or actions.

Other studies appeared to link the GLP-1 med to some unexpected benefits. A new JAMA Network Open study published on Friday involving 1.6 million patients with Type 2 diabetes found that compared with insulin, GLP-1 meds were associated with a significant risk reduction in 10 obesity-related cancers, including gallbladder cancer, liver cancer, ovarian cancer and colorectal cancer.

In that same study, GLP-1 drugs were not associated with a decreased risk of any of the 13 cancers examined when compared with metformin but, instead, an increased risk of kidney cancer.

Meanwhile, Novo Nordisk and its GLP-1 rival Eli Lilly have been busy confirming their offerings’ efficacy in various conditions beyond diabetes and weight loss. Lilly’s GIP/GLP-1 dual agonist Zepbound recently aced a phase 3 study in obese patients with obstructive sleep apnea. Novo’s semaglutide has also shown a benefit in slowing kidney disease progression in diabetic patients with chronic kidney disease. And Wegovy earlier this year secured an FDA approval to reduce the risk of cardiovascular-related events in patients who are overweight or obese with cardiovascular disease.