GLP-1 RAs May Influence Development of Nonexudative AMD in Patients With Obesity

GLP-1 RA usage is associated with a reduction in risk of developing nonexudative age-related macular degeneration (AMD), according to a study comparing GLP-1 RAs, other weight-loss drugs (OWLDs), and no weight-loss medication use.1

Research has long debated the relationship between obesity and AMD, with many examining associations between the conditions by body mass index. Some studies have found no association, while others have found associations solely within specific population subgroups. However, given the anti-inflammatory potential of GLP-1 RAs, research may have a new avenue forward for understanding the connection between these diseases.2

“[GLP-1 RAs], increasingly prescribed for weight loss, have demonstrated systemic anti-inflammatory and neuroprotective benefits, yet their implications for AMD risk remain largely unstudied,” Abhimanyu Ahuja, MD, department of ophthalmology, Casey Eye Institute, and colleagues wrote. “In this study, we evaluated the association between GLP-1 RA use and the risk of developing or progressing AMD, compared with both other weight-loss drugs (OWLDs) and no weight loss therapy.”1

Investigators conducted a retrospective cohort study using deidentified data from TriNetX, a global federated health research network. A total of 2 analyses were conducted, with the first excluding patients with a history of nonexudative AMD and the second excluding patients with a history of exudative AMD. The primary analysis investigated the risk of developing nonexudative AMD, while the secondary analysis assessed the risk of progression to exudative AMD.1

Patients were followed up for ≤10 years from the index event date, defined by medication initiation. The primary outcome was assessed at 5, 7, and 10 years, and the secondary outcome was assessed at 10 years only.1

A total of 91,408 patients were enrolled in the study. After propensity score matching for the primary analysis, the GLP-1 RA cohort included 45,704 patients with a mean age of 61.1 years (standard deviation [SD] 5.76), while the OWLD cohort included 45,704 patients with a mean age of 61 years (SD 5.86).1

Investigators noted an association between GLP-1 RA use and an 83.5% (risk ratio [RR], 0.16; 95% CI, 0.1-0.28; P <.001), 86.7% (RR, 0.13; 95% CI, 0.08-0.22; P <.001), and 91.3% (RR, 0.09; 95% CI, 0.05-0.16; P <.001) reduced risk of developing nonexudative AMD at 5, 7, and 10 years, respectively, versus OWLD use. A subanalysis found no weight-loss medication use associated with a decreased risk at 5 years (RR, 0.47; 95% CI, 0.33-0.67; P <.001), 7 years (RR, 0.52; 95% CI, 0.37-0.72; P <.001), and 10 years (RR, 0.52; 95% CI, 0.39-0.68; P <.001) versus OWLD use.1

The secondary analysis showed an association between both GLP-1 RA use (RR, 0.7; 95% CI, 0.33-1.5; P = .35) and no weight-loss medication use (RR, 0.52; 95% CI, 0.25-1.06; P = .07) and a lower risk of progression to exudative AMD. When compared to the GLP-1 RA group, the no-weight-loss medication group had a higher risk of progressing to exudative AMD (RR, 1.45; 95% CI, 0.68-3.08; P = .33).1

Ahuja and colleagues noted the trial’s inability to determine a causative mechanism for the observed outcomes; however, they highlighted the history of GLP-1 receptors being identified in both the human retina and retinal pigment epithelium. Given the substantial impact AMD has on the retinal photoreceptors and retinal pigment epithelium, which is also intrinsically susceptible to chronic inflammation, GLP-1 RAs may confer retinoprotective benefits and attenuate these inflammatory pathways.1

“These findings may warrant clinical trials assessing the validity of this finding in a randomized fashion, as well as further investigation into plausible biological pathways,” Ahuja and colleagues wrote. “If validated, GLP-1 RAs could be considered in counseling patients with elevated AMD risk who are eligible for pharmacologic weight loss.”1

References

1. Ahuja AS, Paredes AA, Young BK. Glucagon-like peptide-1 receptor agonists and age-related macular degeneration. JAMA Ophthalmology. Published online October 23, 2025. doi:10.1001/jamaophthalmol.2025.3821

2. Peeters A, Magliano DJ, Stevens J, Duncan BB, Klein R, Wong TY. Changes in abdominal obesity and age-related macular degeneration: the Atherosclerosis Risk in Communities Study. Arch Ophthalmol. 2008;126(11):1554-1560. doi:10.1001/archopht.126.11.1554