Study Links GLP-1 Drugs to Lower Macular Degeneration Risk

Cardiometabolic Adjustments Reverse Apparent Eye Risk

Unadjusted health records initially suggested an increased risk of age-related macular degeneration (AMD) among people taking glucagon-like peptide-1 receptor agonists (GLP-1 RAs). That apparent link disappeared and reversed once investigators controlled for underlying cardiovascular and metabolic conditions.

The findings come from a retrospective case-control study presented at the annual meeting of the American Academy of Ophthalmology (AAO) in New Orleans. Franklin Ye Ruan and colleagues from the Carle Illinois College of Medicine evaluated records from more than 300 million individuals in the Epic Cosmos database.

Crude Numbers Versus Adjusted Odds in Large Patient Records

Raw data across the database showed higher unadjusted odds ratios for all primary classifications of age-related macular degeneration. Out of 300,410,753 patient records evaluated, 15,385,073 patients received a prescription for a GLP-1 RA, 1,384,467 patients had AMD, and 115,056 had both diagnoses recorded.

The researchers recorded unadjusted crude odds ratios of 1.68 for any AMD, 1.89 for dry AMD, and 1.53 for wet AMD. These initial numbers reflected raw co-occurrence before taking patient age, weight, or metabolic health into account.

Accounting for Diabetes, Hypertension, and Blood Lipids

Adjusting for common cardiometabolic diagnoses changed the direction of the statistical association between GLP-1 RA medications and AMD. Using Mantel-Haenszel adjustment models, the researchers showed that the higher initial risk was driven by confounding health variables rather than the drug exposure itself.

Accounting for specific health conditions reduced the odds ratios for AMD below baseline values in multiple categories.

• Accounting for type 2 diabetes mellitus produced an odds ratio of 0.69 for any AMD and 0.62 for wet AMD.
• Adjusting for hypertension yielded an odds ratio of 0.65 for any AMD and 0.59 for wet AMD.
• Adjusting for hyperlipidemia resulted in an odds ratio of 0.63 for any AMD and 0.57 for wet AMD.
• The protective reversal after adjustment was most pronounced for wet AMD.

Impact of Patient Age and Body Mass Index

Adjustments for body mass index (BMI) and patient age altered the calculated odds in distinct directions. Controlling for BMI attenuated the odds ratio down to 1.17, which reduced most of the excess risk observed in the unadjusted comparison.

Age adjustments showed a different pattern in the analysis. Controlling for patient age increased the odds ratio to 1.94, confirming that baseline age remains a strong independent driver of retinal changes.

Observational Evidence and Clinical Caveats

The dataset represents an observational case-control analysis of electronic health records rather than a prospective randomized clinical trial. Retrospective coding data can show statistical correlations, but observational studies cannot prove that GLP-1 RAs directly prevent retinal damage.

Ruan noted that the team hopes these findings prompt more rigorous studies on GLP-1 medications and macular degeneration that systematically account for underlying health conditions. Patients with questions about GLP-1 RAs and their vision should discuss their comprehensive metabolic and eye health with their clinician.