Researchers have identified in a new study that exposure to glucagon-like peptide-1 receptor agonists (GLP-1RAs), commonly used for weight management, was associated with a substantially lower risk of early (nonexudative) age-related macular degeneration (AMD) development among nondiabetic individuals with obesity. The analysis found that GLP-1RA exposure was not linked with progression to advanced (exudative) AMD and, therefore, may provide retinal protection in nondiabetic patients. The study was published in JAMA Ophthalmology by Abhimanyu S. and colleagues.
GLP-1RAs like liraglutide and semaglutide have received international acclaim for their ability to treat obesity and enhance metabolic health. Prior studies suggested these medications may decrease AMD risk in patients who were diabetic, but the extent to which this same effect crossed into nondiabetic patients was uncertain. AMD is a major cause of irreversible loss of vision in elderly people, initially presenting as nonexudative (dry) alterations that may advance to exudative (wet) disease, resulting in severe visual impairment. Understanding the mechanism by which GLP-1RAs affect the course of this disease may initiate novel preventive measures for age-related eye diseases.
The research employed a large retrospective cohort of the TriNetX Global Collaborative Network with 91,408 patients aged 55 years or older diagnosed with overweight or obesity but not diabetes between January 2004 and July 2025. The participants were classified into two groups: those who received GLP-1RAs (liraglutide or semaglutide) and those who received other weight-loss medications (OWLDs) like lorcaserin, sibutramine, setmelanotide, fenfluramine, mazindol, orlistat, phentermine, and diethylpropion.
Propensity score matching was conducted for demographic and comorbidity balancing, yielding 45,704 matched patients in both cohorts. The main outcome was the incidence of nonexudative AMD at 5, 7, and 10 years, and secondary outcome measured progression to exudative AMD at 10 years. Risk ratios (RRs) and 95% confidence intervals (CIs) were used to find associations.
Results
After matching, the GLP-1RA arm consisted of 35,753 women (78.2%) and 7,852 men (17.2%) aged 61.1 years on average, whereas the OWLD arm consisted of 35,732 women (78.2%) and 7,815 men (17.1%) aged 61.0 years on average.
Covariate balance was attained for all variables.
The use of GLP-1RA was significantly linked with a lower risk of developing nonexudative AMD at several time points than the use of OWLD.
The risk reduction was most pronounced at 10 years, with users of GLP-1RA having an RR of 0.09 (95% CI, 0.05–0.16; P < 0.001). At 5 and 7 years, the RRs were 0.16 (95% CI, 0.10–0.28; P < 0.001) and 0.13 (95% CI, 0.08–0.22; P < 0.001), respectively.
No significant difference in progression from nonexudative to exudative AMD was found between the groups.
Within this large, multicenter cohort, the use of GLP-1 receptor agonists was found to be significantly protective against the development of nonexudative AMD in nondiabetic obese individuals but with no effect seen on progression to exudative AMD. These results imply that GLP-1RAs have protective effects on the retina and provide novel avenues for ophthalmic preventive care in older, metabolically at-risk populations.
Reference:
Ahuja AS, Paredes AA, Young BK. Glucagon-Like Peptide-1 Receptor Agonists and Age-Related Macular Degeneration. JAMA Ophthalmol. Published online October 23, 2025. doi:10.1001/jamaophthalmol.2025.3821
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