Glucagon-like Peptide-1 Receptor Agonist Impact on Chronic Ocular Disease Including Age-Related Macular Degeneration

Purpose

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to exert neuroprotective and anti-inflammatory effects across multiple organ systems. This study investigated whether GLP-1RAs influence the risk for age-related ocular diseases.

Design

Retrospective cohort study.

Participants

This study used an electronic health records platform of patients in the United States. Patients > 60 years with at least 5 years of ophthalmology follow-up and medication prescription documentation were included. There were 5 medication groups: GLP-1RA, metformin, insulin, statin, or aspirin users. Cohorts were propensity matched (1:1) on demographics and chronic disease risk factors.

Main Outcome Measures

Outcomes of cataract, ocular hypertension, primary open-angle glaucoma, nonexudative age-related macular degeneration (AMD), and exudative AMD were compared 5 years after initial medication prescription. We then examined earlier time points within the 5-year period. Significance was defined as P < 0.05 with a hazard ratio (HR) threshold of > 1.1 or < 0.9.

Results

Of the 9669 patients taking GLP-1RAs, 84.4% had a diagnosis of diabetes with an average body mass index (BMI) of 36.2 kg/m². Propensity-matched cohorts demonstrated that GLP-1RAs were associated with a reduced hazard of nonexudative AMD compared with metformin (HR, 0.68; 95% CI, 0.56–0.84), insulin (HR, 0.72; 95% CI, 0.58–0.89), and statins (HR, 0.70; 95% CI, 0.57–0.87). These findings were validated compared with aspirin and in an independent older cohort of patients. This significant reduction appeared after 3 years compared with metformin (HR, 0.69; 95% CI, 0.52–0.91), insulin (HR, 0.66; 95% CI, 0.5–0.87), and statins (HR, 0.67; 95% CI, 0.51–0.88). Time course results were validated using independent cohorts of propensity-matched patients taking medications for 3 years. Notably, GLP-1RAs also significantly reduced the risk of exudative AMD (HR, 0.70; 95% CI, 0.58–0.84) and primary open-angle glaucoma (HR, 0.58; 95% CI, 0.45–0.76) compared with insulin after 3 years. Use of GLP-1RAs showed no persistent impact on the risk of cataract formation or ocular hypertension compared with other medications.

Conclusions

This study suggests that GLP-1RAs may reduce the risk of multiple age-related ocular diseases and the need for future prospective studies to validate these findings.

Financial Disclosure(s)

Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.