February 15, 2021
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Disclosures: The authors report no relevant financial disclosures.
Metformin use may be associated with a reduced risk for developing age-related macular degeneration, according to study results published in JAMA Ophthalmology.
“Metformin, the most commonly prescribed oral antihyperglycemic drug for diabetes, has been shown to have anti-aging and protective effects against many age-associated diseases. In epidemiology studies, metformin lowers the risk of developing cardiovascular disease, stroke, cancer, dementia and primary open-angle glaucoma,” Andrea L. Blitzer, MD, University of Chicago Medical Center, and colleagues wrote. “Given the known anti-aging effects of metformin and its relatively safe adverse effect profile, we sought to determine if the use of metformin is associated with reduced odds of developing AMD.”
In a case-control study, researchers analyzed 312,404 patients (58.2% women) 55 years and older newly diagnosed with AMD and 312,376 control participants matched 1:1 (55.2% women, 55 years to 107 years old) for development of AMD.
Study results showed metformin use was associated with a reduced risk for developing AMD (OR = 0.94; 95% CI, 0.92-0.96). Further multivariable analysis revealed the association to be dose dependent with the greatest benefit persisting after 2 years of low to moderate dosage (1 g dose to 70 g dose: OR = 0.91, 95% CI, 0.88-0.94; 271 g dose to 600 g dose: OR 0.9, 95% CI, 0.87-0.93; 601 g dose to 1080 g dose: OR = 0.95, 95% CI 0.92-0.98). Researchers noted while metformin use carried decreased risk for AMD development in patients with diabetes without diabetic retinopathy (DR), it was a risk factor in patients with DR (OR = 0.93, 95% CI 0.91-0.95 vs. OR = 1.07, 95% CI 1.01-1.15, respectively).
“Not only does metformin reduce the odds of developing AMD, but this outcome is strongest at low to moderate doses and is only seen in the absence of coexisting DR,” Blitzer and colleagues concluded. “This study highlights metformin as a possible therapeutic intervention to prevent or slow the progression of AMD. Future studies will be important to further validate and confirm this finding.”
Perspective
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Steven Ferrucci, OD, FAAO
AMD is the leading cause of irreversible vision loss in patients older than 50 years, and there is currently no treatment for the dry form other than lifestyle modification and vitamin supplementation. Therefore, any treatment or intervention that may reduce the risk for developing AMD or delay vision loss is important. This study concludes that metformin use, in low to moderate doses, reduces the risk for developing AMD by 5% to 10%.
We should interpret these results with caution. While this study includes a large sample size (in excess of 3 million), it relies on diagnosis codes from billing records that may not always be accurate. Further, because the authors did not have access to the patients’ medical charts, they were unable to ascertain other characteristics, such as ethnicity and HbA1c levels, that may also play a role. Because the data were retrieved from a database that only includes information from private insurances, it may not fully represent the older population.
While promising, more research is needed. The underlying mechanism leading to the observed benefits of metformin in AMD need to be better understood before it could be recommended for the treatment of AMD.
Steven Ferrucci, OD, FAAO
Chief of optometry and residency director, Sepulveda VA Ambulatory Care Center and Nursing Home
Professor, Southern California College of Optometry/Marshall B. Ketchum University
Disclosures: Ferrucci reports he has served on the speakers panel or advisory board for Alcon, Bausch + Lomb, Centervue, Genentech, Maculogix, Regeneron, Optovue and ScienceBased Health.
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