Older adults with diabetes using GLP-1 receptor agonist medications, such as semaglutide and tirzepatide, may face a doubled risk of developing neovascular age-related macular degeneration (nAMD), a potentially blinding eye condition, according to a study published in JAMA Ophthalmology.
The research, conducted from 2020 to 2023, analyzed health records of over 139,000 Ontario residents with an average age of 66 who had diabetes and used GLP-1 drugs for at least six months.
“Our study included any GLP-1 receptor agonists that were prescribed during the study period in Ontario, Canada; we did not exclude any specific type of these medications,” Rajeev H. Muni, MD, principal investigator and associate professor at the University of Toronto, told Medical News Today (MNT). “However, semaglutide represented the vast majority of use in our cohort, accounting for 97.5% of all GLP-1 prescriptions.”
Semaglutide, sold as Ozempic for type 2 diabetes and Wegovy for weight loss, dominated, while lixisenatide, often combined with insulin glargine, made up the remaining 2.5%. Tirzepatide, sold as Mounjaro and Zepbound, was not included as it was not approved in Canada during the study period.
The study found that among diabetic patients aged 66 and older, the incidence of nAMD was about 1 in 1,000 for those not using GLP-1 drugs, compared to 2 in 1,000 for those on the medications for six months or more.
“While the absolute risk remains low, this represents a relative doubling in risk,” Muni said. “While our findings should not prompt alarm, they do warrant increased clinical awareness.”
He advised patients noticing new visual symptoms to consult their doctor and see an ophthalmologist promptly.
The risk of nAMD increased with longer use of GLP-1 drugs.
“We observed a clear dose-response relationship in our analysis, with the risk of nAMD increasing as the duration of GLP-1 receptor agonist exposure increased,” Muni said, per MNT. “Given that many individuals use these medications chronically, whether for blood sugar control or for weight loss, the long-term ocular safety of GLP-1 RAs requires further investigation.”
Demetrios Vavvas, MD, PhD, from Mass Eye and Ear, noted the study’s strength in its large-scale data and dose-response findings but cautioned that it shows only association, not causation, due to unmeasured factors like obesity or smoking.
“The most significant limitation is that this study can only show an association, not prove that the drug causes this eye condition,” Vavvas said.
He also highlighted potential surveillance bias and the low event rate of less than 0.2%.
A separate study in JAMA Ophthalmology, led by Bradley Katz, MD, PhD, from the University of Utah, reported nine patients, averaging 58 years old, who developed vision issues while taking semaglutide or tirzepatide. Seven experienced nonarteritic anterior ischemic optic neuropathy (NAION), one had a retinal stroke, and one had optic nerve swelling without vision loss.
“These drugs are very effective at reducing blood sugar, and when one rapidly reduces blood sugar, it can cause swelling in the optic nerve,” Katz explained, per MNT, suggesting that rapid blood sugar changes may trigger an osmotic shift, causing eye complications.
He recommended gradual dose increases and consulting an ophthalmologist for vision changes.
Howard Krauss, MD, a neuro-ophthalmologist in Santa Monica, recommended annual eye exams for patients with underlying conditions and assessing the optic nerve’s cup-to-disc ratio before starting GLP-1 drugs.
“Those who wish to take an extra step of caution may choose to have an eye exam prior to initiating treatment to determine their ocular health status,” Krauss said, MNT reported.
About one in eight people have used GLP-1 medications, which have surged in popularity for weight loss and diabetes management, according to recent tracking polls. Physicians like Mir Ali, MD, a bariatric surgeon, emphasized the rarity of eye complications but urged awareness.
“As with all medications, if a patient notices a significant change in vision, or any other system, they should contact their prescribing provider,” Ali said, according to MNT.