GLP-1 receptor agonists are being used more frequently for the management of chronic weight. Previous evidence indicated that age-related macular degeneration was less likely among patients with diabetes being treated with a GLP-1 receptor agonist, but data were sparse in nondiabetic individuals. With the increasing obesity and AMD incidence in older adults, clarification of whether GLP-1 receptor agonists affect AMD risk independently of diabetes is clinically important.
This retrospective cohort study used electronic health record data from the TriNetX Global Collaborative Network. It identified adults aged 55 years or older, without diabetes, with overweight or obese between January 2004 and July 2025. In the primary analysis, patients with pre-existing non-exudative AMD were excluded, whereas in the secondary analyses, patients with non-exudative AMD were included, and those with exudative AMD were excluded. Propensity score matching was used to balance demographic and comorbidity characteristics. Data analyses were performed in March and August of 2025.
Patients were stratified according to prescription of GLP-1 receptor agonists, specifically liraglutide or semaglutide, versus other weight-loss drugs such as lorcaserin, sibutramine, setmelanotide, fenfluramine, mazindol, orlistat, phentermine, and diethylpropion.
Results
The primary outcome was incident nonexudative AMD at 5, 7, and 10 years. The secondary outcome was progression to exudative AMD at 10 years.
Risk ratios with 95% confidence intervals were calculated, and standardized mean differences confirmed covariate balance after matching.
It included a total of 91,408 patients. After matching based on the propensity scores, 45,704 patients were analyzed in each cohort.
In our study, the mean age was 61.1 years for the GLP-1RA group and 61.0 years for the OWLD group.
Females comprised 78.2% of both the cohorts.
GLP-1 receptor agonist use was associated with a significantly reduced risk of nonexudative AMD compared with other weight-loss drugs:
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
10 years: RR 0.09, 95% Confidence Interval, 0.05–0.16; P < .001
No statistically significant differences were observed in progression from nonexudative to exudative AMD at 10 years.
In adults with obesity but without diabetes, the long-term risk of developing nonexudative age-related macular degeneration was markedly lower with use of GLP-1 receptor agonists, whereas no effect was seen on progression to exudative AMD. The current data suggest a potential ocular benefit of the GLP-1 receptor agonists and form a basis for future randomized studies on their role in the prevention of AMD.
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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