A new study has found that semaglutide, the active ingredient in the popular weight loss drugs Ozempic and Wegovy, may be linked to a type of sudden vision loss called non-arteritic anterior ischemic optic neuropathy (NAION).
The study, which hasn’t been published in a peer-reviewed journal, is the second to suggest a link between semaglutide and the condition, a small vessel “stroke” of the optic nerve that usually leads to permanent blindness. There are about 6,000 new cases every year.
Experts said, however, that the new research shouldn’t necessarily dissuade people from trying semaglutide or other glucagon-like peptide-1 (GLP-1) agonists, a class of medications that also includes the diabetes and weight loss drugs Zepbound and Mounjaro.
“Although there are some interesting studies on the topic, it is premature to conclude that the association between semaglutide and NAION is a causal association,” Andrew Lee, MD, spokesperson for the American Academy of Ophthalmology and a neuro-ophthalmologist at Houston Methodist Hospital, told Health.
The researchers wanted to study the association between semaglutide and NAION after the previous paper highlighted a connection between the two, Anton Pottegård, MSc, PhD, DMSc, a researcher at Odense University Hospital and author of the new study, told Health. “This was initiated based on the [earlier study] from the U.S.,” Pottegård said.
That study, published in July, relied on data from 710 people with type 2 diabetes, 979 of whom were overweight or obese.
The study authors divided participants in each category into two subcategories—those who had received a semaglutide prescription and those who hadn’t—and found that the semaglutide cohorts in both the type 2 diabetes and overweight/obesity groups experienced higher rates of NAION.
“That study is seemingly well conducted,” Pottegård said, “but it is using a dataset that is quite peculiar, in that they only have data from patients that at some point had a contact to a specialist ophthalmologist [or neuro-ophthalmologist], which renders it quite difficult to draw conclusions from.”
Another study limitation was that the researchers didn’t know whether all participants prescribed semaglutide took the drugs as intended, Pottegård explained.
For the new study, Pottegård and his team analyzed data from 44,517 people in Denmark and 16,860 people in Norway, all of whom were eligible for semaglutide for the management of type 2 diabetes. Among the semaglutide users in Denmark, 24 people developed NAION; in Norway, there were eight cases.
Researchers found that of 10,000 semaglutide users, one additional person may develop NAION over the course of a year than would typically be diagnosed with the disease. Participants therefore had a higher risk of NAION when taking semaglutide, the researchers concluded, but “the absolute risk remains low.”
“I think this is a worthwhile study to pay attention to when it is peer-reviewed and published,” Beverly Tchang, MD, an endocrinologist and assistant professor of clinical medicine at Weill Cornell Medicine and obesity medicine advisor at Ro, told Health. “The investigators performed several analyses to address potential confounders and selection bias and came to a similar conclusion as [the previous study], that NAION may be linked to semaglutide or GLP-1s.”
That said, Tchang agreed, “the overall risk of NAION, regardless of GLP-1 use, seems to be very low.”
“A person would have a very, very low chance of being that one in 10,000 person,” she said.
Experts stressed that we have no reason to assume semaglutide causes NAION. “There is a biologically plausible mechanism for GLP-1 to cause worsening diabetic eye problems from tighter blood sugar control analogous to the worsening of diabetic retinopathy in similar patients,” Lee said. “The issue, however, is that association is not causation—and diabetes mellitus is a known risk factor for NAION.”
Right now, NAION is not listed as a known side effect of semaglutide, Pottegård said. “These are among the first studies to investigate this phenomenon,” he explained. “Now, regulators will evaluate the findings to see whether it should be listed. From my reading of the literature, including both our studies and other studies on this, I find it highly likely that it will be recognized as a side effect.”
Given that the research is still in its infancy, it’s unclear how compounded semaglutide—that is, drugs with ingredients mixed together to meet a person’s special needs—may affect NAION risk, experts said.
Research linking NAION to semaglutide use shouldn’t deter people from taking the medication if their doctor recommends it, experts said.
People who have a history of NAION may want to consult their healthcare providers about the risks of semaglutide.
“For the vast majority of users, there is no reason to consider this rare side effect,” Pottegård said. “However, for patients with a history of NAION or patients experiencing NAION during treatment, they should know this is likely associated with their use of semaglutide and stop using the drug.”
As research on the relationship between NAION and semaglutide use evolves, experts may learn more about those most at risk. “Hopefully, in the future, we will better understand this and be able to point to specific patient subgroups at risk,” Pottegård said.
Until then, people who qualify for semaglutide should consider the benefits and risks of taking the medication.
“More research is necessary to test the hypothesis,” Lee said. Until we have that, “patients should be aware of this information and, in consultation with their care team, make a careful, informed choice based on their individual risk profile.”
