A Canadian cohort study has found that older adults using GLP-1 receptor agonists may face a higher risk of developing neovascular age-related eye condition that causes vision loss.
A newly unveiled Canadian retrospective cohort analysis has shed fresh light on a troubling trend — older adults administering GLP-1 receptor agonists, most notably semaglutide variants such as Rybelsus, Ozempic, and Wegovy, may be encountering a modest escalation in the likelihood of developing neovascular age-related macular degeneration (nAMD) — a grave ocular affliction tied to severe visual decline.
Individuals grappling with type 2 diabetes who engaged in GLP-1 usage for at least half a year showed heightened odds of acquiring nAMD when compared with peers who steered clear of the drug, tracked over a triannual span. As per the figures detailed by Dr. Reut Shor and her cohort at the University of Toronto, the adjusted hazard ratio clocked in at 2.21 (95% CI: 1.65–2.96).
“The risk appeared to inch upward the longer patients were on these agents,” Dr. Shor conveyed to MedPage Today, underscoring her unease at the contrast between the drug’s broad cardiovascular promise and this unexpected ocular pitfall.
Though the absolute incidence remained relatively diminutive — 0.2% among users versus 0.1% in non-users — the weight of the potential consequences looms large. “nAMD is no light matter. It severely impacts vision integrity and overall life quality,” Shor cautioned.
Biochemical Clues Point Toward Vascular Disruption
While the biological causality still eludes precision, hypotheses are brewing. A sudden systemic drop in blood glucose — including retinal glucose — might evoke a transient oxygen-deficient retinal state. However, researchers speculate that a prolonged hazard could stem from escalated levels of the chemokine CXCL12, which may incite vascular endothelial growth factor (VEGF) production — the very compound known to foster abnormal blood vessel growth behind the retina.
As Dr. Brian VanderBeek from the University of Pennsylvania insightfully put it, “There’s no such thing as a free ride. The therapeutic benefits are real, yes, but physicians must not turn a blind eye to the hidden adversities lurking in these medications.”
A Nod to Past Warnings: A Pattern Emerging
Dr. VanderBeek’s accompanying editorial resurfaced earlier clinical data that had already suggested a tenuous link between GLP-1 drugs and diabetic retinal deterioration. The inconsistency puzzled many at the time since nearly every other diabetic marker had improved under GLP-1 therapy. One theory speculated that a rapid normalization of glucose levels might paradoxically worsen eye health, especially in individuals previously overlooked by placebo trials.
More recent rumblings include an uptick in nonarteritic ischemic optic neuropathy (NAION) — a condition where blood flow to the optic nerve gets restricted. Though mechanistic clarity is lacking, suspicion points toward autonomic blood pressure shifts induced by GLP-1 agents, possibly stifling ocular perfusion.
Study Scope, Numbers, and Nuances
This real-world data originated from Ontario’s public health registry (2020–2023), targeting individuals aged 66 and up. A sample of 139,002 patients was examined, where diabetics using GLP-1 agonists for a minimum of six months were paired 1:2 with those who hadn’t used the drugs.
Across the board, the mean age hovered at 66, with women representing 47% of the sample. Most participants had been battling diabetes for around six years, and nearly two-thirds also contended with hypertension.
Results exposed a duration-dependent hazard. Users who stayed on GLP-1 therapy beyond 30 months saw their risk skyrocket (HR: 3.62), while those between 18–30 months bore a doubled risk (HR: 2.26), compared to minimal impact for shorter-term users (6–18 months; HR: 0.94).
Dr. VanderBeek remarked, “Jumping from no AMD to full-blown nAMD in three years is a stretch. This strongly hints at the presence of preclinical or early-stage AMD in the study base that may have amplified progression.”
Implications for Broader Populations and Drug Classes
The study’s limitations warrant careful thought. It didn’t dissect risks across specific GLP-1 subtypes or account for dosage intricacies, delivery routes, or injection frequency. Notably, semaglutide dominated 97.5% of prescriptions in the research cohort. A negligible fraction had taken lixisenatide (Adlyxin) — now discontinued.
Dr. Shor’s team advised against blanket conclusions, emphasizing the necessity for future investigations to factor in baseline AMD levels, and to probe whether such adverse reactions are confined to diabetics — or may spill over to those using GLP-1 drugs solely for weight management or off-label applications.
Conclusion
As enthusiasm for GLP-1 receptor agonists continues to balloon, this emerging signal on possible sight-threatening repercussions calls for sharper vigilance. With visual health on the line, researchers and prescribers alike must tread thoughtfully — balancing benefits with the subtle perils still under investigation.