Better known as the antidiabetic-slash-weight loss drugs Ozempic and Wegovy, semaglutide has become something of a ‘wonder drug,’ with research regularly discovering its additional medical benefits. However, a new study has found that the drug potentially has a serious downside.
New research led by the Massachusetts Eye and Ear Hospital (Mass Eye and Ear) found that semaglutide use was associated with nonarteritic anterior ischemic optic neuropathy (NAION), or ‘eye stroke,’ a condition that can cause sudden vision loss.
“The use of these drugs has exploded throughout industrialized countries and they have provided very significant benefits in many ways, but future discussions between a patient and their physician should include NAION as a potential risk,” said Joseph Rizzo, MD, director of the Neuro-Ophthalmology Service at Mass Eye and Ear and the Simmons Lessell Professor of Ophthalmology at Harvard Medical School, and the study’s senior author.
NAION is a relatively rare condition caused by impaired blood circulation to the optic nerve (what 'ischemic' refers to in the condition's name), which transmits information from the eye to the brain. It’s called ‘nonarteritic’ because the reduced blood flow isn’t associated with true blood vessel inflammation (as seen in arteritis). ‘Anterior’ refers to the front-most part of the optic nerve, where it meets the eye, while ‘optic neuropathy’ is because it causes injury to the optic nerve, leading to sudden, painless vision loss. In severe cases, NAION can cause blindness. There is no current treatment for the condition.
The exact mechanism that causes NAION isn’t known. What is known is that the condition is seen more often in patients with diabetes, high blood pressure, and sleep apnea. After noticing a rise in patients taking semaglutide presenting with vision loss caused by NAION, the researchers undertook a retrospective study to investigate whether there was a link between the two.
Semaglutide mimics a naturally produced hormone called glucagon-like peptide 1 (GLP-1). It connects with GLP-1 receptors in the body, lowering blood sugar levels and making people feel fuller and less hungry.
The researchers examined data from 16,827 Mass Eye and Ear patients seen by neuro-ophthalmologists – medical doctors who specialize in treating vision issues linked to neurological conditions – between December 2017 and November 2023. The average age was 47, and 52% were female. The patients were divided into those with type 2 diabetes and those who were overweight or obese. Those groups were then further divided into those prescribed semaglutide or a non-GLP-1 medication to treat their respective conditions. None of the participants had a history of NAION.
Propensity matching – a statistical matching technique that attempts to estimate the effect of a treatment by accounting for covariates that predict receiving the treatment – was used to assess whether prescribed semaglutide was associated with NAION. Factors such as sex, age, high blood pressure, type 2 diabetes, obesity, obstructive sleep apnea, high blood lipids and coronary artery disease were accounted for.
Among 710 participants with type 2 diabetes, 194 were prescribed semaglutide, and 516 were prescribed a non-GLP-1 antidiabetic medication. The researchers found that 17 NAION events occurred in patients prescribed semaglutide versus six in the patients taking non-GLP-1 meds. The cumulative incidence of NAION over three years was 8.9% for the semaglutide-prescribed group compared to 1.8% for the non-GLP-1-prescribed group. These findings suggest that type 2 diabetics prescribed semaglutide were four times more likely to be diagnosed with NAION.
Of the 979 overweight or obese participants, 361 were prescribed semaglutide, and 618 were prescribed a non-GLP-1 weight loss medication. For these patients, 20 NAION events occurred in the patients prescribed semaglutide and three occurred in the non-GLP-1-prescribed cohort. The cumulative incidence of NAION over three years was 6.7% in the semaglutide group and 0.8% in the non-GLP-1 group, meaning they were seven times more likely to develop the condition.
There are limitations to the study. All participants attended Mass Eye and Ear, which sees a high number of people with rare eye diseases. They were mostly white, and the number of NAION cases seen over the study period was relatively small. Additionally, the researchers couldn’t determine whether participants actually had their prescriptions dispensed or had started taking semaglutide and then stopped.
Further, as this is an observational study, the researchers could not say that semaglutide caused an increased risk of developing NAION, just that the data suggest an association between the two. Further research is needed to assess causality.
“Our findings should be viewed as being significant but tentative, as future studies are needed to examine these questions in a much larger and more diverse population,” Rizzo said. “This is information we did not have before, and it should be included in discussions between patients and their doctors, especially if patients have other known optic nerve problems like glaucoma or if there is preexisting significant visual loss from other causes.”
The study was published in the journal JAMA Ophthalmology.
Source: Mass Eye and Ear