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

To evaluate the association between glucagon-like peptide-1 receptor agonist (GLP-1RA) use and the incidence of age-related macular degeneration (AMD) and neovascular AMD (nAMD) among adults with diabetes.

Retrospective, propensity score-matched cohort study.

Adults with diabetes who initiated a GLP-1RA or another noninsulin antidiabetic agent. In Epic Cosmos, 2 797 686 GLP-1RA users were matched 1:1 to 2 797 686 active comparators.

We analyzed de-identified electronic health record data from Epic Cosmos and independently replicated the primary analyses in the University of California Health Data Warehouse. Individuals with prevalent AMD or nAMD and those with prior anti-VEGF treatment were excluded. One-to-one nearest-neighbor propensity score matching balanced demographics, diabetes duration, comorbidities, smoking, diabetic retinopathy, obesity, and eye-care utilization. Cumulative incidence at 1, 5, and 10 years was estimated using Kaplan-Meier methods, and adjusted associations were evaluated using multivariable Cox proportional hazards models.

Incidence of any AMD and nAMD.

In the matched Epic Cosmos cohort (total N = 5 595 372), GLP-1RA use was associated with lower cumulative incidence of any AMD at 1 year (0.187% [95% confidence interval {CI}, 0.182%-0.192%] vs. 0.294% [95% CI, 0.287%-0.301%]), 5 years (0.924% [95% CI, 0.907%-0.941%] vs. 1.278% [95% CI, 1.260%-1.296%]), and 10 years (5.561% [95% CI, 4.719%-6.549%] vs. 6.540% [95% CI, 6.017%-7.108%]); all P < 0.001. Unadjusted cumulative incidence of nAMD was also lower among GLP-1RA users at 1 year (0.047% vs. 0.065%), 5 years (0.280% vs. 0.340%), and 10 years (1.874% vs. 2.393%); all P < 0.001. In multivariable Cox models, GLP-1RA use was independently associated with lower hazard of any AMD (hazard ratio [HR], 0.84; 95% CI, 0.83-0.86; P < 0.001) and was not associated with an increased hazard of nAMD (HR, 1.00; 95% CI, 0.97-1.04; P = 0.79). In the independent University of California Health Data Warehouse cohort, GLP-1RA use was likewise associated with lower AMD incidence at 5 and 10 years, whereas nAMD incidence did not differ significantly between groups.

Among adults with diabetes, GLP-1RA use was associated with lower incident AMD and was not associated with increased nAMD risk. These findings provide reassurance regarding ocular safety and support a potential protective association for earlier AMD phenotypes.

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