Potential Efficacy of Metformin for Age-Related Macular Degeneration: A Systematic Review and Meta-Analysis

Topic: Metformin, a widely used diabetes medication, has shown potential for treating age-related macular degeneration (AMD) due to its antioxidative, anti-inflammatory, and antiangiogenic properties. This study aims to systematically review and analyze the efficacy of metformin in reducing AMD prevalence. Clinical Relevance: Metformin's potential to serve as a treatment for AMD could significantly reduce the burden of vision loss, offering a cost-effective and widely accessible solution. Methods: A systematic search was conducted in OVID Embase, OVID MEDLINE, Cochrane Library, and Web of Science databases on May 2, 2024. Both observational and interventional studies were included if they involved oral metformin use before AMD diagnosis. Data were extracted and analyzed using a random-effects model meta-analysis, with subgroup analyses based on study design, AMD subtype, sex, and metformin dosage. Results: Eighteen observational studies were identified, which together included a total of 2 683 234 individuals. Nine studies had a case-control design, 7 were retrospective cohort studies, and 2 were cross-sectional studies. The meta-analysis revealed a significant reduction in the odds of AMD among metformin users (pooled odds ratio [OR]- 0.86, 95% confidence interval-0.79-0.93, P-0.0002, I2-90%). The association was significant in both patients with diabetes (pooled OR-0.89) and without diabetes (pooled OR-0.70), although only 2 studies reported nondiabetic ORs. Dose-response analysis revealed significant protective effects at low doses. Sensitivity analysis indicated that the removal of an outlier study did not alter the overall effect. Bias analysis using the Risk of Bias in Nonrandomized Studies of Interventions tool revealed significant risks of bias, particularly due to confounding. Conclusion: Although the current evidence suggests a potential protective role of metformin in AMD, all studies showing an effect of metformin have been observational and thus subject to bias. Randomized clinical trials are needed to determine the effectiveness of metformin for preventing the onset of AMD. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. Ophthalmology Science 2025;5:100741 (c) 2025 by the American Academy of Ophthalmology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).