PURPOSE: To investigate the risk of neovascular age-related macular degeneration (AMD) in patients taking glucagon-like peptide-1 receptor agonists (GLP-1RAs).
DESIGN: A retrospective cohort study.
PARTICIPANTS: This study used the TriNetX network, a large aggregated electronic health records platform from health care organizations across the United States. Adults over the age of 60 years with ≥1, 2, or 3 years of ophthalmology follow-up and medication prescription documentation were included.
METHODS: Patients were grouped into those taking GLP-1RAs, alternate glucose-lowering medications, and alternate lipid-lowering medications. Cohorts were propensity matched on demographics, chronic disease prevalence, and disease severity indicators.
MAIN OUTCOME MEASURES: The primary outcomes were risk of developing nonneovascular and neovascular AMD at 1, 2, and 3 years after initial medication prescription. A secondary analysis evaluated the risk of neovascular AMD in patients with nonneovascular AMD at baseline. Significance was defined as P < 0.05 and hazard ratio (HR) threshold >1.1 or <0.9 to minimize noise in large data sets.
RESULTS: Patients prescribed GLP-1RA had greater baseline chronic disease burden and worse disease severity metrics than comparator groups. Propensity matching effectively matched chronic disease prevalence at baseline. Glucagon-like peptide-1 receptor agonist prescription was associated with a significant reduction in risk of nonneovascular AMD compared with glucose-lowering medications over 1 (HR, 0.79; 95% confidence interval [CI], 0.66-0.94), 2 (HR, 0.75; 95% CI, 0.64-0.88), and 3 (HR, 0.77; 95% CI, 0.66-0.91) years. Similar protective effects were observed when compared with lipid-lowering medications after 2 (HR, 0.84; 95% CI, 0.71-0.99) and 3 (HR, 0.8; 95% CI, 0.68-0.94) years. There was a significant reduction in risk of neovascular AMD with GLP-1RA prescription across all time points compared with both alternate glucose-lowering and lipid-lowering medications. However, there was no significant impact of GLP-1RA on the risk of conversion from nonneovascular AMD at baseline to neovascular AMD.
CONCLUSIONS: These findings suggest that GLP-1RAs may provide protective effects against nonneovascular AMD and, importantly, did not show an increased risk of neovascular AMD. Future prospective trials are needed 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.
