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Association of Metformin Use With Age–Related Macular Degeneration
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Analysis of data from a large commercial and Medicare database found a correlation between low to moderate metformin use over 2 years and a decreased risk for developing age-related macular degeneration (AMD). Interestingly, a higher dose (>1080 g) had no association with developing AMD, while the presence of diabetic retinopathy increased the risk of developing AMD in patients taking metformin.
- Based on these data, metformin may be used as a preventive therapy for AMD. Additional research in this area is warranted.
abstract
This abstract is available on the publisher's site.
Access this abstract nowImportance
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.
Additional Info
Disclosure statements are available on the authors' profiles:
Association of Metformin Use With Age-Related Macular Degeneration: A Case-Control Study
JAMA Ophthalmol 2021 Jan 21;[EPub Ahead of Print], AL Blitzer, SA Ham, KA Colby, D SkondraFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Eye Care
Blitzer and coauthors utilized “big data” studying the association between metformin use and development of age-related macular degeneration (AMD). This study found a statistically decreased odds of developing AMD in patients who take metformin. This finding is significant for understanding the mechanism of action (MOA) by metformin and for providing therapeutic potential for AMD. However, in the discussion of possible underlying mechanisms of this association, there are some inconsistent explanations. For instance, in comparison with a published case–control study,1 the efficacy of metformin in reducing AMD development in the current study is only 1/8 of that reported in the previous study. The authors explained that this discrepancy is due to inclusion of much sicker patients in the previous report. The severity of comorbidities in individuals was defined by the Charlson Comorbidity Index (CCI), and included diabetes severity. In other words, the authors believe that poorly controlled diabetic patients may show higher beneficial effects of metformin on developing AMD. However, when the authors explained why the high-dose metformin group has essentially no reduction in developing AMD in their own study, they claimed that “poorly controlled diabetes may benefit less from metformin use.” Nevertheless, if we lay aside these inconsistent discussions, the significant findings of this study and the previous report have prompted us to consider a clinical trial answering whether metformin has a protective effect in those at risk for developing AMD.
Reference