Glucagon-Like Peptide-1 Receptor Agonist Use and Risk of Neovascular Age-Related Macular Degeneration in a National...

To investigate the risk of neovascular age-related macular degeneration (AMD) in patients taking glucagon-like peptide-1 receptor agonists (GLP-1RAs).

A retrospective cohort study.

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.

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.

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.

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.

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.

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