Do GLP-1RAs alter the risk of developing age-related macular degeneration (AMD)?

Prior studies have suggested that glucagon-like peptide-1 receptor agonist (GLP-1RA) use reduce age-related macular degeneration (AMD) risk in patients with diabetes, but whether this is true in populations without diabetes is unknown. These agents are increasingly being used to lose weight, but their ocular effects in individuals without diabetes remain unclear.1 To examine this issue, US researchers evaluated the risk of developing nonexudative AMD and its progression to exudative AMD in patients with obesity but without diabetes prescribed GLP-1RAs compared with other weight-loss drugs and no weight-loss medication use.1The retrospective cohort study used electronic health record data obtained from the multicentre TriNetX Global Collaborative Network, which includes data on more than 170 million patients across 147 healthcare organizations worldwide. The study included patients 55 years of age or older diagnosed with overweight or obesity, but not diabetes, from January 2004 to July 2025.1 For the primary analysis, patients with preexisting nonexudative AMD were excluded. For the secondary analysis, patients with preexisting nonexudative AMD were included, while those with preexisting exudative AMD were excluded. Propensity score matching balanced baseline demographics and comorbidities.1 Patients in the study were prescribed a GLP-1RA (liraglutide or semaglutide) or other weight-loss drugs (lorcaserin, sibutramine, fenfluramine, mazindol, phentermine, diethylpropion [all never or no longer marketed in Canada], setmelanotide [Imcivree] and orlistat [Xenical]).1The primary outcome was development of nonexudative AMD at five, seven and 10 years. The secondary outcome was progression to exudative AMD at 10 years. Risk ratios (RRs) with 95% confidence intervals [CIs] were calculated. Standardized mean differences were used to assess covariate balance after matching.1Key results:The study included 91,408 patients.After propensity score matching for the primary analysis, 45,704 patients remained in each of the two cohorts: GLP-1RA cohort (78.2% female; mean age 61.1 years) and other weight-loss drugs cohort (78.2% female; mean age 61.0 years).In the primary analysis, compared with use of other weight-loss drugs, GLP-1RA use was associated with a reduced risk of developing nonexudative AMD: 83.5% reduced risk at five years (RR, 0.16; 95%CI, 0.10–0.28; p < 0.001), 86.7% at seven years (RR, 0.13; 95%CI, 0.08–0.22; p < 0.001) and 91.3% at 10 years (RR,0.09; 95%CI, 0.05–0.16; P < .001).In the subanalysis, compared with use of other weight-loss drugs, use of no weight-loss medication was associated with a decreased risk of nonexudative AMD at five years (RR, 0.47; 95% CI, 0.33–0.67; p < 0.001), seven years (RR, 0.52; 95%CI, 0.37–0.72; p < 0.001), and 10 years (RR, 0.52; 95% CI, 0.39–0.68; p < 0.001).Conversely, compared with GLP-1RA use, use of no weight loss medication was associated with an increased risk of nonexudative AMD at five years (RR, 2.96; 95%CI, 1.93–4.55; p < 0.001), seven years (RR, 4.02; 95%CI, 2.85–5.69; p < 0.001) and 10 years (RR, 4.30; 95%CI, 3.09–5.99; p < 0.001).Similar patterns were observed in the sensitivity analyses assessing risk of exudative AMD and any form of AMD.In the secondary analysis, no differences were observed in progression to exudative AMD.1The authors conclude that in this cohort study of patients with obesity but not diabetes, GLP-1RA use was associated with reduced risk of developing nonexudative AMD. However, GLP-1RA use did not prevent progression to exudative AMD in the cohort of patients with existing nonexudative AMD. The authors believe their results warrant conducting future randomized controlled clinical trials to assess the validity of these findings. If their results are confirmed, they contend that GLP-1RAs could be considered an option for patients with elevated AMD risk who are eligible for weight-loss therapies.1An accompanying commentary highlights the degree of risk reduction of AMD found in this study in patients taking GLP-1RAs (i.e., > 80% at 5 years and increasing with the later time points up to 10 years), compared with other weight-loss drugs. This reduction in AMD risk is essentially unprecedented and raises several questions about the methodology and selected outcome. It is important to critically look at the study design and database limitations to understand how confounding, bias and chance could have influenced the results. Although the commentary acknowledges that useful information can be obtained from studies with large numbers of patients, such as this one, it identifies several potential study design flaws that could have affected the results.2 ReferencesAhuja AS, Paredes III AA, Young BK. Glucagon-like peptide-1 receptor agonists and age-related macular degeneration. JAMA Ophthalmol 2025; published online October 23, 2025. (accessed October 23, 2025).Talcott KE, Rachitskaya AV, Singh RP. Glucagon-like peptide-1 receptor agonist use and age-related macular degeneration—where do we stand? JAMA Ophthalmol 2025; published online October 23, 2025. (accessed October 23, 2025).

Do GLP-1RAs alter the risk of developing age-related macular degeneration (AMD)?

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