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

Ophthalmol Retina. 2025 Aug 11:S2468-6530(25)00354-9. doi: 10.1016/j.oret.2025.07.018. Online ahead of print.

ABSTRACT

OBJECTIVE: 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.

DESIGN: Retrospective cohort study.

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

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

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

RESULTS: After propensity score matching, the main cohort analysis included 7,496 patients, of whom 3,748 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. Use for ≥ 6 consecutive years showed consistent protective effects; 1-4 years showed weaker associations.

CONCLUSION: 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.

PMID:40803555 | DOI:10.1016/j.oret.2025.07.018