Glucagon-like peptide (GLP-1) receptor agonists (GLP-1 RAs) are transformative medications for millions of people managing diabetes and obesity. Amid research demonstrating the many benefits gained from these drugs and a rapid increase in their use worldwide, new evidence from a retrospective study raises concerns about a possible link between these medications and increased risk of serious eye disease.
Higher Risk of Macular Degeneration
Research conducted at the University of Toronto and published in JAMA Ophthalmology found that people with diabetes who used GLP-1 RAs had double the risk of developing neovascular age-related macular degeneration (nAMD) compared to non-users.
AMD is a leading cause of irreversible vision loss among older adults, affecting approximately 196 million people globally. While the more common dry AMD progresses slowly, the wet form, nAMD, leads to rapid and permanent vision loss.
The study analyzed data from more than 139,000 patients with diabetes, aged 66 or older, who were monitored over a three-year period. Among them, 46,334 patients had taken GLP-1 RAs for at least six months, and 92,668 had no exposure to the drugs.
Among GLP-1 RA users in the study, 97.5% were taking a Novo Nordisk GLP-1 RA semaglutide medication, and 2.5% were taking a similar drug from Sanofi. Among the GLP-1 RA users, 0.2% (93 people) developed nAMD, compared to 0.1% of non-users (88 people). Although the absolute risk was low, prolonged use of a GLP-1 RA drug was associated with increased risk.
“These findings expand upon the growing body of literature raising concerns regarding the potential ocular safety of systemic GLP-1 RA use in patients with diabetes,” researchers noted, emphasizing that the study reported associations, not direct causality.
Broader Ocular Safety Questions Emerge
This isn’t the first instance of heightened concerns about GLP-1 therapies and eye health. Previous research published in JAMA Ophthalmology revealed that individuals using GLP-1 drugs faced a significantly increased risk of nonarteritic anterior ischemic optic neuropathy (NAION), a severe eye condition characterized by sudden vision loss due to reduced blood flow to the optic nerve.
Prompted by those findings, the European Medicines Agency (EMA) conducted its own assessment, subsequently recommending that the labeling for semaglutide include NAION as a “very rare” potential side effect, occurring in approximately one in 10,000 users.
Balancing Risks and Benefits
Despite these concerning findings, researchers note that the overall incidence of serious eye disease remains relatively low among GLP-1 RA users. Nevertheless, they advocate for increased vigilance and regular ophthalmologic screening, especially among older patients and those with prolonged exposure to GLP-1 RA therapies.
The researchers emphasized the need for further research to clarify the underlying mechanisms by which GLP-1 medications may affect eye health. Understanding these processes will enable patients and healthcare providers to better balance the substantial benefits of GLP-1 therapies, such as effective diabetes management and weight loss, against their potential ocular risks.
By proceeding with caution amid continued investigations, the medical community can better ensure that patients continue to reap the substantial benefits of these therapies while effectively managing and mitigating associated risks.
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