Is there an association between metformin use and the development of age-related macular degeneration (AMD)?
In this large case-control study using a national database of patients, we found that metformin use was associated with decreased odds of developing AMD in a dose-dependent manner, with the greatest benefit at low to moderate dosages.
The use of metformin may protect against the development of AMD and lead to a novel therapeutic strategy for the prevention of this disease.
Age-related macular degeneration (AMD), the leading cause of irreversible blindness in older adults, appears to have no effective preventive measures. The common antidiabetic drug metformin has been shown to have protective outcomes in multiple age-associated diseases and may have the potential to protect against the development of AMD.
To determine whether metformin use is associated with reduced odds of developing AMD.
Design, Setting, and Participants
This case-control study of patients from a nationwide health insurance claims database included a population-based sample of patients. Those aged 55 years and older with newly diagnosed AMD from January 2008 to December 2017 were defined as cases and matched with control participants. Data analyses were completed from June 2019 to February 2020.
Dosage of metformin and exposure to other prescribed medications, as identified from outpatient drug claims.
Main Outcomes and Measures
Risk of developing AMD.
A total of 312 404 affected individuals were included (181 817 women [58.2%]). After matching, 312 376 control participants were included (172 459 women [55.2%]; age range, 55 to 107 years). The case group had a slightly higher percentage of participants with diabetes (81 262 participants [26.0%]) compared with the control group (79 497 participants [25.5%]). Metformin use was associated with reduced odds of developing AMD (odds ratio [OR], 0.94 [95% CI, 0.92-0.96]). This association was dose dependent, with low to moderate doses of metformin showing the greatest potential benefit (dosages over 2 years: 1-270 g, OR, 0.91 [95% CI, 0.88-0.94]; 271-600 g, OR, 0.90 [95% CI, 0.87-0.93]; 601-1080 g, OR, 0.95 [95% CI, 0.92-0.98]). Doses of more than 1080 g of metformin over 2 years did not have reduced odds of developing AMD. Both the reduction in odds ratio and the dose-dependent response were preserved in a cohort consisting only of patients with diabetes. Metformin use was associated with a decreased OR of AMD in patients with diabetes without coexisting diabetic retinopathy (OR, 0.93 [95% CI, 0.91-0.95]) but was a risk factor in patients with diabetic retinopathy (OR, 1.07 [95% CI, 1.01-1.15]).
Conclusion and Relevance
In this study, metformin use was associated with reduced odds of developing AMD. This association was dose dependent, with the greatest benefit at low to moderate doses. When looking only at patients with diabetes, we saw a preservation of the dose-dependent decrease in the odds of patients developing AMD. Metformin does not appear to be protective in patients with diabetes and coexisting diabetic retinopathy. This study suggests that metformin may be useful as a preventive therapy for AMD and provides the basis for potential prospective clinical trials.
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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.
Accepted for Publication: November 11, 2020.
Published Online: January 21, 2021. doi:10.1001/jamaophthalmol.2020.6331
Corresponding Author: Dimitra Skondra, MD, PhD, Department of Ophthalmology and Visual Science, University of Chicago Medical Center, 5841 S Maryland Ave, Chicago, IL 60637 (firstname.lastname@example.org).
Author Contributions: Dr Skondra and Ms Ham had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: All authors.
Acquisition, analysis, or interpretation of data: Blitzer, Ham, Skondra.
Drafting of the manuscript: Blitzer, Ham.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Ham.
Administrative, technical, or material support: Colby.
Supervision: Colby, Skondra.
Conflict of Interest Disclosures: None reported.
Funding/Support: This work was supported by a grant from The University of Chicago Institute for Translational Medicine (Dr Skondra).
Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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