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

Abstract

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.

Keywords: Age-related macular degeneration; Aging; Drug repurposing; GLP-1 receptor agonist; Glaucoma.