Are Weight Loss Drugs Linked to Blindness?
The popular prescription drug semaglutide (sold as Ozempic and Wegovy) has helped many patients with obesity or type 2 diabetes lose weight. Since their approval by the United States Food and Drug Administration (FDA) in 2019 and 2017, respectively, demand has skyrocketed for both drugs.
The active ingredient in both, however, may be linked to sudden blindness. Mass General Brigham researchers observed that patients prescribed semaglutide, the active ingredient in both drugs, had an increased risk of nonarteritic anterior ischemic optic neuropathy (NAION), a nerve disease capable of causing blindness.
Joseph Rizzo, MD, a Mass General Brigham ophthalmologist, found that people with diabetes who had been prescribed semaglutide were more than 4 times more likely to be diagnosed with NAION than people with diabetes who didn’t take semaglutide. Those who were prescribed the drug and had overweight or obesity, he found, were more than 7 times more likely to receive the diagnosis than patients with overweight or obesity who didn’t take semaglutide.
“To be perfectly clear, I would not take my findings and use them to recommend that patients stop taking their medications,” says Dr. Rizzo. “Our finding was really the first possible significant negative finding with these drugs. It may just merit extra caution in the consideration between doctors and patients about who may use this medicine.”
Dr. Rizzo sees patients with complex vision disorders at Mass Eye and Ear. He explains what NAION is and how semaglutide may trigger the condition.
How does semaglutide treat diabetes and obesity?
What is NAION?
According to Dr. Rizzo, more than 1 million nerve fibers along the optic nerve relay visual signals from the eyes to the brain. Damaged fibers can disrupt the crucial eye-brain connection, leading to blindness.
According to the American Academy of Ophthalmology (AAO), NAION is the most common cause of sudden or severe (acute) optic nerve injury in people older than 50. That said, it is not commonly found among the general population, nor do doctors fully understand what causes it.
Dr. Rizzo likens the condition to a “stroke” of the optic nerve. It occurs suddenly, and it can happen without warning. However, he tells patients not to take the term “stroke,” too literally. Strokes and heart attacks occur from a blockage to one main artery, restricting oxygen from reaching vital organs.
“There are so many vessels in the eye that it would be reasonable to think a stroke could never occur near the optic nerve,” says Dr. Rizzo. “If one of those vessels was blocked, blood and oxygen could probably reach it through another vessel.”
Damage to the optic nerve and subsequent blindness are permanent.
Why do researchers suspect a link between NAION and semaglutide?
A conversation with a group of trainees led Dr. Rizzo to investigate the popular weight loss drugs.
At Mass Eye and Ear, he regularly gathers trainees in the morning to review patient cases and discuss diagnoses and treatments. One morning, he mentioned a patient with NAION who happened to have taken semaglutide.
“I thought it was purely anecdotal, until a resident who had come up from the emergency room said, ‘Well, I just saw the same thing,’” he adds. “When I saw a third such case that next week, I knew this was too far out of the ordinary.”
Dr. Rizzo wanted to determine if the cases belonged to a larger, more troubling trend. He teamed up with Seyedeh Maryam Zekavat, MD, PhD, the Mass General Brigham trainee who observed the second NAION case, and several other trainees to analyze the records of 17,000 Mass Eye and Ear patients treated since the FDA first approved Ozempic.
They separated cases into two groups: those of patients with obesity or overweight and those of patients with diabetes. The researchers then distinguished cases by whether a patient had taken semaglutide or another weight loss drug, and whether NAION had occurred.
Their study evaluated more than 600 patients diagnosed with NAION over a 6-year span.
How could semaglutide affect the eyes?
Dr. Rizzo’s study is the first to associate semaglutide with NAION.
Not knowing exactly what causes NAION makes it even more difficult to understand the drug’s role in developing the condition.
“On the one hand, we’re committed to exploring a definitive cause-and-effect relationship,” says Dr. Rizzo. “On the other, we’re trying to understand how this class of medicine could possibly trigger the condition.”
Dr. Rizzo weighs some possible explanations.
Changes to blood sugar levels
The optic nerve needs oxygen from its surrounding blood vessels to function.
High levels of blood sugar can damage these vessels, compromising the health of the nerve. According to Dr. Rizzo, a rapid change in blood sugar can lead to similar damage.
“For someone with type 2 diabetes, their body may be accustomed to having higher than normal blood sugar,” he says. “If those levels drop too quickly, the period of metabolic adjustment can make cells vulnerable to injury.”
Reduced blood pressure
According to Dr. Rizzo, some ophthalmologists attribute NAION to high blood pressure (hypertension). Blood flowing too fast can overwhelm and damage vessels leading to the optic nerve. But, like an abrupt change in blood sugar levels, an abrupt change in blood flow may shock those vessels, leading to similar damage.
Semaglutide, which can lower blood pressure in patients, may trigger a similar reaction, Dr. Rizzo speculates.
“Both hypotheses may be compelling factors, but do they explain the whole picture?” he says. “I don’t think so. It’s likely much more nuanced.”
Determining the relationship between semaglutide and NAIOIN
Understanding the full effects of the drug, Dr. Rizzo believes, will help patients better weigh the risks of their treatment before accepting their prescription.
“If a patient already has visual loss, let's say from prior trauma or glaucoma or retinopathy related to diabetes, then I think an understanding that these medicines potentially would increase the risk of further visual loss can go a long way toward shared decision-making between doctors and patients,” says Dr. Rizzo.
Dr. Rizzo is designing a larger clinical trial to determine the exact relationship between the drug and NAION. The trial will try to account for several statistical limitations and biases in his initial research, which include:
Low NAION case numbers: The number of NAION cases seen over the 6-year study period was relatively small.
Non-representative sample: Mass Eye and Ear sees an unusually high number of patients with rare eye diseases, as opposed to a non-specialty hospital.
Lack of diversity: A large majority of the patients were white.
His research will include the expertise of researchers at the Harvard School of Public Health, as well as epidemiologists, pharmacologists, and endocrinologists from across Mass General Brigham.
“I consider our study an important first step,” says Dr. Rizzo. “This next study may be imperfect, too, but it’s advantages will bring us closer to fully understanding what we consider to be the capital-T truth of the relationship in question.”
