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Original Investigation
January 21, 2021

Association of Metformin Use With Age-Related Macular Degeneration: A Case-Control Study

Author Affiliations
  • 1Department of Ophthalmology and Visual Science, University of Chicago Medical Center, Chicago, Illinois
  • 2Center for Health and the Social Sciences, The University of Chicago, Chicago, Illinois
  • 3Department of Ophthalmology, New York University, New York
JAMA Ophthalmol. 2021;139(3):302-309. doi:10.1001/jamaophthalmol.2020.6331
Key Points

Question  Is there an association between metformin use and the development of age-related macular degeneration (AMD)?

Findings  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.

Meaning  The use of metformin may protect against the development of AMD and lead to a novel therapeutic strategy for the prevention of this disease.


Importance  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.

Objective  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.

Exposures  Dosage of metformin and exposure to other prescribed medications, as identified from outpatient drug claims.

Main Outcomes and Measures  Risk of developing AMD.

Results  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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    1 Comment for this article
    Metformin in Macular Degeneration.
    Gary Ordog, MD, DABEM, DABMT | County of Los Angeles, Department of Health Services, (retired)
    Thank you for your extensive study of metformin use and association with Macular Degeneration. The fact that you found that there was an inverse dose relationship with metformin use suggests to me that there is a confounding variable at play here. Also, that it is not metformin is not associated with MD reduction in people with diabetes supports this. Thus, the lower metformin doses are associated with milder diabetic disease, the higher metformin doses associated with more MD and worse diabetes, so, you are looking at not so much an inverse dose relationship (spurious) but an association between severity of diabetes and the development of MD. In my opinion, the current recommendations for the use of metformin should remain the same while the use of metformin for the prevention of MD and other complications of aging should be reserved for further study. Again, thank you. Gary Joseph Ordog, MD.