Metformin Linked to Lower Risk of Dementia

Benefit strongest in African-American veterans. Metformin's mechanism for reducing inflammation throughout the body may explain the link.

Older African American Man wearing a black hatResearchers found that metformin may reduce the risk of cognitive decline in African Americans, especially men. (Photo: Unsplash, Fred Kearney)

Diabetes increases the risk of dementia, and African-American patients are at higher risk of cognitive decline after a diagnosis of type 2 diabetes than are white patients. Now, a new study suggests that choosing the right diabetes drugs may help reduce that risk, especially among African-Americans.1

Researchers looked at the medical records of more than 73,000 veterans, ages 50 and up, who used the Veterans Health Administration (VHA) from 2000 to 2015, explains study leader Jeffrey Scherrer, PhD, a researcher at the Columbia Missouri VAMC and professor of family and community medicine at the St. Louis University School of Medicine.

All patients were free of both dementia and diabetes medication during the years 2000 and 2001. After that, those with diabetes were prescribed either metformin or sulfonylurea.
After accounting for other factors, Dr. Scherrer found that metformin use was most strongly linked with a lower risk of dementia in African-American veterans.

"In the youngest [African-American] age group [50-64] , there was about a 40% reduced risk of developing dementia over the followup period," Dr. Scherrer tells OnTrack Diabetes. Among African-Americans 65 to74, metformin use was linked with a 29% lower risk of getting dementia.

Among white patients 65 to 74, there was a 10% lower risk, but no link was found for the other two age groups of white men. And no link was found between metformin and dementia in any of those patients 75 and older.

Researchers' Perspective

The finding is especially interesting since type 2 diabetes is nearly twice as prevalent among African-Americans as non-Hispanic whites, the researchers say.1

When age is factored in, 13.4% of African-Americans develop type 2 diabetes compared to 7.3% of whites. And with this comes an increased risk of dementia, which is 10% to 18% higher in African-Americans than in whites with type 2 diabetes.3

For these reasons, finding a way to reduce that risk, especially in African-Americans, is crucial.

What Previous Research Found

Findings from other studies have come up with conflicting results. Some have found that metformin is linked with an 8 to 10%  decrease in dementia risk overall.4,5

At least one study did focus on differences in the link between metformin and dementia between white and African-American patients.4 Those researchers found the dementia risk declined in white patients ages 65-74 but not African-Americans.4

However, the study did not include patients under age 65, and that is where the protective effects may kick in, Dr. Scherrer says.  For that reason, the researchers decided to look at a wider age range.

In another study published in 2018, Australian researchers pooled the result of 14 studies already published, an approach called a meta-analysis, and found 3 studies showing metformin reduced cognitive impairment and 6 showed reduction in dementia diagnoses. Some other studies, however, found negative or neutral effects.6

However, that review concludes that, overall, metformin should be kept as first line treatment for those with diabetes and a risk of dementia.

Explaining the Link

Dr. Scherrer can't say for sure why the metformin was found to reduce dementia risk more than the other medication. He does not think it is solely due to lowering of the A1C, the test that looks back at blood sugar control for the past 2-3 months.

"Metformin has a general anti-inflammatory effect which is beneficial for reducing the development of adverse outcomes in many organs of the body," he tells OnTrackDiabetes.

More About the Patients

Overall, nearly 86% of the group was white and more than 14% African-Americans. The researchers took into account factors such as high blood pressure, stroke, congestive heart failure, mental health issues such as depression and other issues that could affect the dementia risk.

The results held.

Expert Perspective

Jared Campbell, PhD, a researcher at the University of New South Wales, Australia, was involved in the Australian meta-analysis that looked at 14 studies, finding mixed results for metformin and reduction of dementia risk.

He reviewed the new study. "This is not the first study to show an apparent beneficial effect for metformin on dementia, but findings have varied and sometimes been contradictory, so it is very exciting to see work beginning to identify which patients may experience benefits."

He can only speculate as to why the benefit was greater in African-Americans. He says that metformin can reduce vitamin B12 level, which can itself increase dementia risk, and Caucasians are more likely than African-Americans to have low vitamin B12 levels to begin with.7

"This may be part of the explanation for why this study found that African Americans had a large apparent benefit," he tells OnTrack Diabetes.

Take Home Points

As the authors notes, there are no existing medications to treat dementia, and the substantial risk they found with reducing that risk among African-American patients may mean that the medication should be broadly prescribed.1

Those recently diagnosed with type 2 diabetes, Dr. Scherrer says, may want to ask their doctor about the value of being on metformin while  also focusing on the lifestyle changes recommended, such as exercising regularly, losing weight if needed and following a healthy diet.

"They many want to go on metformin earlier," he says, depending on their doctor's advice, ''although that is just speculation."

For someone with diabetes already taking another diabetes drug, he says, they might want to ask their doctor if they should be switched to metformin or it should be added.

Dr. Campbell says talking to your doctor should be the first step. "Metformin is already a first line drug for the treatment of diabetes, but there can be medical reasons that individuals should avoid it."  And, for those who are taking metformin and are at risk of dementia, he also suggests asking your doctor if your vitamin B12 levels are healthy.

More About the Medicines

Sulfonylureas work by increasing insulin release from the beta cells in the pancreas, thus lowering blood sugar. Some examples are DiaBeta, Amaryl and Tolinase. 8

Metformin works by reducing the amount of sugar your liver releases and also helps your boy respond better to insulin. Examples include Glucophage, Glumetz and Fortamet.9

Neither Dr. Scherrer nor Dr. Campbell have any relevant disclosures

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