Antihyperglycemic drug linked to reduced risk of new onset AMD

This article was reviewed by Andrea Blitzer, MD

Reduction in the risk of developing age-related macular degeneration (AMD) may be another benefit of metformin for protecting against age-related diseases, according to a case-control study undertaken by a team of investigators at the University of Chicago.

Led by Dimitra Skondra, MD, PhD, an associate professor in the Department of Ophthalmology and Visual Science, the research analyzed 10 years of data from the IBM MarketScan Commercial and Medicare Supplemental databases.

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It found that the strongest effect occurred at low to moderate doses of metformin, was not restricted to patients with diabetes, but was not present among patients with diabetes who had diabetic retinopathy.

Andrea Blitzer, MD, a member of Skondra’s team and an ophthalmology resident at the University of Chicago, presented the findings at the Association for Research in Vision and Ophthalmology 2020 virtual annual meeting.

“Further studies are needed to confirm the protective benefit that we identified for metformin and to investigate the underlying pathways,” she said. “If our findings are confirmed in clinical trials, the research may lead to a novel therapeutic strategy for this blinding disease.”

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Impetus for research
Previous studies found that metformin reduced the incidence of diabetes mellitus, diabetes-related mortality, cardiovascular diseases, cancer, dementia, and all-cause mortality. It has also been reported to reduce the risk of glaucoma.

“Metformin targets mediators and pathways that affect inflammation, cell survival, stress defense, oxidative stress,” Blitzer said. “All of these can play a role in health span and longevity, and a number of the pathways and mediators that are targets for metformin have also been implicated in the pathogenesis of AMD.”

Blitzer noted that these details led to Skondra’s study investigating whether metformin decreases the risk of developing AMD using a big data approach.

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Study details
The cases and controls for the research were identified through a search of the MarketScan database for the years 2008 to 2017. The study looked at people 55 years of age or older who had newly diagnosed AMD.

A control subject was selected for each case from among a pool of 31 million patients and matched by age, comorbidities, and region of the United States. The investigators were able to determine metformin usage based on claims data.

The study looked at a total of 312,404 cases that were then matched with controls. Compared with the controls, patients with AMD were more likely to smoke, to have hyperlipidemia, and to have diabetic retinopathy.

In a multivariate model adjusting for risk factors and other medications, the use of metformin significantly decreased the risk of being newly diagnosed with AMD within 2 years by 6%.

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With stratification by metformin dose, patients who had received low to moderate doses had the greatest risk reduction (9% and 10%, respectively).

Because metformin is primarily used as an antihyperglycemic drug, the investigators also analyzed the data to see if the potential protective effect of metformin on AMD development occurred only in the cohort of patients with diabetes. They found that the protective effect was similar in the diabetic cohort as in the overall cohort.

With cases more likely than controls to have diabetic retinopathy, another analysis considered if the presence of this ocular complication of diabetes was an important factor for metformin’s risk reduction. The benefit of metformin only occurred in the absence of diabetic retinopathy, the team reported.

Finally, a protective benefit of other antihyperglycemic medications and statins was investigated.

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In multivariate models, other diabetic medications seemed to have a mild protective effect as well, but metformin remained protective even in multivariate analysis adjusting for the effects of other medications

“Metformin is a well tolerated and is the most commonly used oral medication to treat diabetes,” Skondra concluded. “The findings from our team may uncover a role for its use as a possible therapeutic intervention for AMD as well.”

Read more by Cheryl Guttman Krader

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Dimitra Skondra MD, PhD
e:dskondra@bsd.uchicago.edux
Skondra has no relevant financial interests to report.

Andrea Blitzer, MD
e:andrea.blitzer@uchospitals.edu
Blitzer has no relevant financial interests to report.