A new study has found that semaglutide, the active ingredient in the popular weight loss drugs Ozempic and Vegovi, may be linked to a type of sudden vision loss called non-arteritic anterior ischemic optic neuropathy (NAION).
The study, which was not 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, however, said the new research should not necessarily dissuade people from trying semaglutide or other glucagon-like peptide-1 (GLP-1) agonists, a class of drugs that also includes the diabetes and weight-loss drugs Zepbound and Mounjaro.
“Although there are some interesting studies on this topic, it is premature to conclude that the link between semaglutide and NAION is causal,” said Andrew Lee, MD, a spokesman for the American Academy of Ophthalmology and a neuro-ophthalmologist at Houston Methodist Hospital. , said Health.
The researchers wanted to study the relationship between semaglutide and NAION after previous work highlighted a link between the two, Anton Pottegard, MSc, PhD, DMScsaid a researcher at Odense University Hospital and author of the new study Health. “This was initiated based on (an earlier study) from the US,” Pottegaard 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 the participants in each category into two subcategories—those who received a prescription for semaglutide and those who did not—and found that the semaglutide cohorts in the type 2 diabetes and overweight/obesity groups had higher rates of NAION.
“That study was apparently well conducted,” Pottegaard said, “but it uses a data set that is quite unusual in that they only have data from patients who at some point had contact with a specialist ophthalmologist (or neuro-ophthalmologist), which makes it quite difficult to perform conclusions.”
Another limitation of the study was that the researchers did not know whether all the participants who were prescribed semaglutide took the medication as intended, Pottegaard explained.
For the new study, Pottegard and his team analyzed data from 44,517 people in Denmark and 16,860 people in Norway, all of whom were eligible for semaglutide to treat type 2 diabetes. Among semaglutide users in Denmark, 24 people developed NAION; in Norway there were eight cases.
The researchers found that out of 10,000 semaglutide users, one more person may develop NAION within a year than would normally 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 look out for when it’s peer-reviewed and published,” Beverly Chang, MDendocrinologist and assistant professor of clinical medicine at Weill Cornell Medicine and consultant in obesity medicine at Ro, he said Health. “The researchers performed several analyzes to address potential confounding factors and selection bias and reached a similar conclusion to (the previous study), that NAION may be associated with semaglutide or GLP-1.”
That said, Chang agreed, “the overall risk of NAION, regardless of GLP-1 use, appears to be very low.”
“A person would have a very, very small chance of being one in 10,000,” she said.
Experts emphasized that we have no reason to assume that semaglutide causes NAION. “There is a biologically plausible mechanism for GLP-1 to cause worsening of diabetic eye problems due to tighter blood sugar control analogous to worsening of diabetic retinopathy in similar patients,” Li said. “The problem, however, is that association is not causation—and diabetes mellitus is a known risk factor for NAION.”
Currently, NAION is not listed as a known side effect of semaglutide, Pottegard said. “These are among the first studies to investigate this phenomenon,” he explained. “Now regulators will assess the findings to see if they should be cited.” Based on my reading of the literature, including our studies and other studies on this, I think it is very likely that this will be recognized as a side effect.”
Because the research is still in its infancy, it’s unclear how compound semaglutide — that is, drugs with ingredients mixed together to meet a person’s specific needs — might affect the risk of NAION, experts say.
Research linking NAION to the use of semaglutide should not dissuade people from taking the drug if their doctor recommends it, experts say.
People with a history of NAION may want to consult with their healthcare provider about the risks of semaglutide.
“For the vast majority of users, there is no reason to consider this rare side effect,” Pottegaard said. “However, for patients with a history of NAION or patients who develop NAION during treatment, they should know that it is likely related to their use of semaglutide and stop using the drug.”
As research on the relationship between NAION and semaglutide use develops, experts may learn more about those most at risk. “Hopefully in the future we will understand this better and be able to pinpoint specific subgroups of patients at risk,” Pottegaard said.
Until then, people who qualify for semaglutide should consider the benefits and risks of taking the drug.
“More research is necessary to test the hypothesis,” Lee said. Until we do, “patients should be aware of this information and, in consultation with their care team, make careful, informed choices based on their individual risk profile.”