Long-Term Metformin Use and Reduced Risk of Age-Related Macular Degeneration: A Large Database Study

To evaluate the association between metformin use and the risk of developing age-related macular degeneration (AMD) among patients with diabetes, with a focus on exposure duration and AMD subtypes.

Retrospective cohort study.

Patients were identified from the TriNetX network using International Classification of Diseases, 10th Revision, and Current Procedural Terminology codes for diabetes and ophthalmic care. Patients aged ≥60 years with diabetes and no documentation of AMD were included in the cohort.

Patients were required to have no AMD diagnoses at 2 eye care visits ≥1 year apart, with the second visit serving as the index event for analysis. The main exposure was yearly metformin use for ≥5 years, with subanalysis up to 10 years. The outcome was incident AMD. Propensity score matching controlled for potential confounders, including demographics, comorbidities, medications, laboratory values, and health care utilization. The association between metformin and AMD was assessed using survival analysis. Results were reported as hazard ratios (HRs) with 95% confidence intervals (CIs).

The primary outcome was a new diagnosis of AMD. Secondary outcomes included a new diagnosis of dry AMD and wet AMD.

After propensity score matching, the main cohort analysis included 7496 patients, of whom 3748 had ≥5 consecutive years of metformin use. Incident AMD was documented in 122 (3.3%) patients who had been exposed to metformin and 184 (4.9%) who had not (HR, 0.68; 95% CI, 0.54-0.85). The metformin group had lower rates of both dry AMD (HR, 0.69; 95% CI, 0.53-0.90) and wet AMD (HR, 0.84; 95% CI, 0.50-1.39), although the association with wet AMD was not statistically significant. The metformin use for ≥6 consecutive years showed consistent protective effects; 1 to 4 years showed weaker associations.

Prolonged metformin use in patients with diabetes was associated with a reduction in AMD risk in this claims database. These findings suggest a potential protective role for metformin, warranting further exploration of its long-term effects on AMD prevention.

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