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

Nov 6, 2025Ophthalmology. Retina

Use of Diabetes Drug That Activates GLP-1 Receptors and Risk of New Blood Vessel Growth in Age-Related Macular Degeneration

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Abstract

Prescription of glucagon-like peptide-1 receptor agonists is associated with a significant reduction in the risk of nonneovascular age-related macular degeneration over 1, 2, and 3 years.

Patients prescribed GLP-1RAs exhibited a greater baseline burden of chronic disease compared to those taking other glucose-lowering or lipid-lowering medications.
After matching for chronic disease prevalence, GLP-1RA use was linked to a reduced risk of developing nonneovascular AMD compared to alternate glucose-lowering medications, with hazard ratios of 0.79, 0.75, and 0.77 at 1, 2, and 3 years, respectively.
Similar reductions in risk for nonneovascular AMD were observed when comparing GLP-1RAs to lipid-lowering medications, with hazard ratios of 0.84 and 0.80 at 2 and 3 years, respectively.
A significant reduction in risk of neovascular AMD was also noted with GLP-1RA prescription across all time points in comparison to both glucose-lowering and lipid-lowering medications.
No significant increase in the risk of conversion from nonneovascular to neovascular AMD was associated with GLP-1RA use.

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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.

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

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