Glucagon-Like Peptide-1 Receptor Agonists and Age-Related Macular Degeneration

Importance Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used for weight loss, but their ocular effects in nondiabetic individuals remain unclear. Prior studies suggest GLP-1RA use reduced age-related macular degeneration (AMD) risk in patients with diabetes, but applicability to nondiabetic populations is unknown. Objective To evaluate the risk of developing nonexudative AMD and its progression to exudative AMD among patients with obesity but not diabetes prescribed GLP-1RAs compared with those prescribed other weight-loss drugs (OWLDs). Design, Setting, and Participants This retrospective cohort study used electronic health record data obtained from the multicenter TriNetX Global Collaborative Network on patients aged 55 years or older diagnosed with overweight or obesity but not diabetes from January 2004 to July 2025. 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. Data were analyzed on March 21, 2025, and August 2, 2025. Exposures Patients were prescribed either the GLP-1RAs liraglutide or semaglutide or OWLDs including lorcaserin, sibutramine, setmelanotide, fenfluramine, mazindol, orlistat, phentermine, and diethylpropion. Main Outcomes and Measures The primary outcome was development of nonexudative AMD at 5, 7, and 10 years. The secondary outcome was progression to exudative AMD at 10 years. Risk ratios (RRs) with 95% CIs were calculated. Standardized mean differences were used to assess covariate balance after matching. Results A total of 91 408 patients were included. After propensity score matching for the primary analysis, 45 704 patients remained in each of the GLP-1RA and OWLD cohorts. The GLP-1RA cohort included 35 753 (78.2%) females and 7852 (17.2%) males with a mean (SD) age of 61.1 (5.76) years, while the OWLD cohort included 35 732 (78.2%) females and 7815 (17.1%) males with a mean [SD] age of 61.0 (5.86) years. Covariate balance was achieved across all variables for the GLP-1RA and OWLD cohorts in the primary analysis. GLP-1RA use was associated with reduced risk of nonexudative AMD compared with OWLDs at 5 years (RR, 0.16; 95% CI, 0.10-0.28; P < .001), 7 years (RR, 0.13; 95% CI, 0.08-0.22; P < .001), and 10 years (RR, 0.09; 95% CI, 0.05-0.16; P < .001). No differences were observed in progression to exudative AMD. Conclusions and Relevance In this cohort study, GLP-1RA use was associated with reduced risk of developing nonexudative AMD but was not associated with progression to exudative AMD among individuals with nonexudative AMD. These findings may inform future randomized trials evaluating the ocular effects of GLP-1RAs in nondiabetic populations.