People with diabetes who were taking GLP-1 drugs had a low but elevated risk of an age-related eye disease that can sometimes lead to blindness, a new observational study concludes, adding to a short list of concerns about eye health in people taking the powerful medications.
The research, published Thursday in JAMA Ophthalmology, found that after one year, more than twice as many people on GLP-1 drugs developed neovascular age-related macular degeneration compared to similar people who were not taking the drugs. The risk was 0.2% in people taking GLP-1s and 0.1% in those who didn’t. Participants, drawn from health records of nearly 140,000 patients in Canada, were matched for socioeconomic status and a long list of conditions in addition to diabetes.
AMD is a leading cause of irreversible blindness in older people; the study participants were 66 years old, on average. Neovascular AMD is an advanced form of the disease (nAMD), known for its abnormal growth of blood vessels and damage to the central part of the retina called the macula. It can be treated with frequent injections to potentially restore or stabilize vision.
People at risk for nAMD share the same conditions — chronic heart failure and chronic kidney disease — that make patients with diabetes candidates for GLP-1s. Aware of other eye problems in people taking GLP-1s, researchers looked for a relationship between the drugs and AMD.
“Seeing such a clear signal in our study was striking,” co-author Reut Shor of the University of Toronto told STAT. “The absolute risk remains low, but the advanced form of AMD is a condition with serious implications for vision and quality of life. So a doubling of risk is clinically meaningful, particularly for vulnerable populations like older adults who may already be at elevated baseline risk.”
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Famous for their success in helping people lose weight, GLP-1 drugs were originally intended to control their blood sugar. Since then, they’ve shown promise in countering cardiovascular disease, hypertension, Parkinson disease, and substance use disorders.
As their use has taken off, though, more eye problems have been reported, including abnormal blood vessel growth. It’s not unusual for rare side effects to show up when more people take a drug.
Cases of this retinopathy were noted in two studies of people with diabetes, cardiovascular risk, and a history of GLP-1 usage for 20 or 24 months. The risk of nonarteritic anterior ischemic optic neuropathy, when the optic nerve’s blood flow is blocked, was also found to be higher in people on GLP-1s.
If there’s a common cause, researchers speculate that it might be plunging blood glucose levels spurred by GLP-1s that trigger abnormal blood vessel growth in the retina. The new study can’t prove that, or even connect cause and effect, its authors emphasize, but their results add to concern about safety and eye health of people being treated for diabetes.
Diabetes itself has long been known to cause retinal degeneration because of too much blood sugar, something that drugs like the standby metformin have been able to control. The issue with GLP-1s may go beyond blood sugar, though.
There are GLP-1 receptors in the retina, the authors write, and GLP-1 drugs increase the levels of molecules that lead to harmful blood vessel formation.
The new study raises questions about whether direct or indirect effects are driving the increased risk of nAMD. The next steps for the research would ideally include studies in animal models and human tissue to determine the mechanism, as well as large, prospective clinical studies in diverse populations to further clarify causality, Shor said. It would also be important to study people without diabetes who are using GLP-1s for weight loss.
For now, Shor said, these results should not cause alarm or abrupt changes in prescribing, but they do warrant greater awareness and appropriate monitoring.
That means patients should promptly report any new visual symptoms, such as blurred or distorted vision, straight lines appearing wavy, or new blind spots. These symptoms could indicate early signs of AMD, Shor said, and should trigger an immediate referral to an ophthalmologist for evaluation.
Whether discontinuing the drug at that point would lessen risk for AMD remains an open question that future research might answer.
Brian L. VanderBeek of the Scheie Eye Institute at the University of Pennsylvania said further research is also needed to pin down the association between the drug and higher rates of eye disease. In a companion editorial, he points out that follow-up studies of diabetic retinal disease and neuropathy in people taking GLP-1s showed the risks were lower than initially thought. But the new paper does cause concern. If its findings are borne out, he writes, as many as 1 in 1,000 GLP-1 users might develop nAMD.
“GLP-1 RAs have had a tremendous role in the care of patients with diabetes and now those needing additional help with weight management,” VenderBeek writes. “While certainly not outweighing the good these medications offer, prescribing physicians need to keep in mind the real and serious ocular adverse events that may occur.”
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