GLP-1 Agonists Shown to Reduce AMD Risk, Progression in Type 2 Diabetes Patients

The reduced AMD risk in patients with type 2 diabetes taking GLP-1 receptor agonists was observed between five and 10 years after treatment initiation. Photo: NEI. Click image to enlarge. To date, multiple studies have provided evidence of a potential protective effect of GLP-1 receptor agonists on the incidence of age-related macular degeneration (AMD), including one published last month involving a national cohort. Recently, another investigation appearing in the journal Retina evaluated how the popular drug impacts the risk of AMD development and progression, specifically among patients with type 2 diabetes. In this population, GLP-1 agonist use was associated with a 15% reduced risk of developing dry AMD and a 20% lower risk of wet AMD compared to other antidiabetic medications.This retrospective cohort study used a global health research network, including a diverse pool of over five million patients with type 2 diabetes. After propensity score matching, 600,816 patients on GLP-1 therapy were compared with an equal number on other therapies, such as insulin. Among these, 27,104 patients had pre-existing early or intermediate nonexudative AMD assessed for progression. The average age of participants was approximately 58 years, 55% were female and 60% were white. The cohort receiving GLP-1 agonist therapy exhibited slightly higher baseline hemoglobin A1c and BMI metrics, which were effectively balanced through propensity score matching.The data revealed that the use of GLP-1 agonists was associated with significant reductions in both the incidence and progression of AMD among patients with type 2 diabetes. Specifically, the researchers observed a 15% reduction in the risk of developing nonexudative AMD and a 20% decrease in the incidence of exudative AMD compared to those receiving alternative diabetes therapies.Furthermore, for patients already diagnosed with early or intermediate nonexudative AMD, GLP-1 therapy led to a notable 29% relative risk reduction in progression to advanced nonexudative AMD and a 27% reduction in the progression to exudative AMD. These protective benefits were observed to occur approximately five years after initiating GLP-1 treatment, with sustained efficacy extending through a decade. It’s worth noting that these positive effects were only seen in patients taking long-acting GLP-1 receptor agonists (more commonly prescribed) and not in those using short-acting agents. Interestingly, the latter “carried an increased risk in developing nonexudative AMD, which was only observed after 10 years,” the researchers noted in their paper. They explained, “While there have been no studies examining the effect of short-acting vs. long-acting GLP-1RAs on AMD, “long-acting agents are known to be more effective in terms of glycemic control and body weight, and it has been suggested that weight-loss mediated pathways may drive the ocular benefits associated with GLP-1RA use.” However, they pointed out that this study cohort was matched for hemoglobin A1c and BMI, which decreases “the likelihood that the more pronounced benefit associated with long-term agents is due to these factors alone.”Moreover, in obese and non-obese individuals, GLP-1 agonist therapy exhibited comparable reduced risks of dry (21% vs. 20%) and wet (19% vs. 26%) AMD, further supporting the idea that the pronounced protective effect of GLP-1 drugs on the disease cannot be solely attributed to glycemic control or weight management. The researchers argued, “The increased risk associated with short-acting analogs needs further studies to validate these findings.”The possible protective effect of GLP-1 receptor agonists against AMD may be primarily attributed to their ability to mitigate chronic retinal inflammation and oxidative stress, which are pivotal in the pathogenesis of AMD, the authors explained in their paper. Previous research indicates that GLP-1 drugs effectively reduce oxidative stress levels, inhibit the production of proinflammatory cytokines and modulate the recruitment of immune cells, thereby alleviating the inflammatory environment within the retina. “Therefore,” they wrote, “our findings may be explained by evidence suggesting that GLP-1RAs exert their effects, in part, by regulating several proinflammatory pathways.”In summary, while this study suggests GLP-1 therapy for patients with type 2 diabetes may portend a reduced risk of incident AMD and slow progression of AMD, future research is needed to validate these findings, as well as investigate the drug’s effect on AMD in non-diabetic patients.Click here for the journal source. McLaughlin SA, Davila N, Shields C, et al. Impact of GLP-1 receptor agonists for type 2 diabetes mellitus on the development and progression of age-related macular degeneration. Retina. 2025;45:2241-51. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.