Metformin, a drug that has been used since the 1950s to treat diabetes, has been shown to have anti-inflammatory effects that could protect against many age-related diseases. This part of the story isn’t new — in fact, we’ve reported on it here.
But can it be — should it be — prescribed to people without diabetes? Can its ability to slow down aging be tested and validated?
As reported here, a clinical trial that would answer these questions has been designed, and some funding is already under way.
The issue is serious, because the FDA does not currently recognize “aging” as a disease to be treated. It only recognizes individual age-related conditions like cardiovascular and cognitive issues, diabetes and others. But if the clinical trial takes place, all that could change.
To understand how big this could be, let’s first review the status of metformin itself. From the article: “Metformin was first used to treat diabetes in the 1950s in France. The drug is a derivative of guanidine, a compound found in Goat’s Rue, an herbal medicine long used in Europe. The FDA approved metformin for the treatment of type 2 diabetes in the U.S. in the 1990s.”
Today metformin, which costs less than a dollar a day, is taken by millions.
Further research on metformin produced some surprising results, as noted by Steven Austad, a senior scientific advisor at the American Federation for Aging Research who studies the biology of aging: “A meta-analysis that included data from dozens of studies, found people who took metformin had a lower risk of several types of cancers, including gastrointestinal, urologic and blood cancers. Austad also points to a British study that found a lower risk of dementia and mild cognitive decline among people with type 2 diabetes taking metformin. In addition, there’s research pointing to improved cardiovascular outcomes in people who take metformin including a reduced risk of cardiovascular death.”
The trouble is, Austad points out, “most of the evidence is observational, pointing only to an association between metformin and the reduced risk. The evidence stops short of proving cause and effect. Also, it’s unknown if the benefits documented in people with diabetes will also reduce the risk of age-related diseases in healthy, older adults.”
That’s where the new clinical study would come in. It’s called The TAME Trial, and it will test whether metformin can “promote a longer healthspan in healthy, older adults.”
The goal, according to Steve Kritchevsky, a professor of gerontology at Wake Forest School of Medicine, who is a lead investigator for the Tame Trial, is to “better understand the mechanisms and pathways by which metformin works in the body.”
For example, researchers will study “how the drug may help improve energy in the cells by stimulating autophagy, which is the process of clearing out or recycling damaged bits inside cells.” They’ll also look at how may “help reduce inflammation and oxidative stress, which may slow biological aging.”
To learn all this, the goal is to enroll 3,000 people between the ages of 65 and 79, for a six-year trial. But it’s an expensive process — between $45 and $70 million, according to Dr. Nir Barzilai of Albert Einstein College of Medicine, who leads the effort to get the trial started.
“The main obstacle with funding this study,” he says, “is that metformin is a generic drug, so no pharmaceutical company is standing to make money.” Barzilai has lined up some pledges from philanthropists and foundations, such as the National Institute on Aging.
The implications are huge: “Currently the FDA doesn’t recognize aging as a disease to treat, but the researchers hope this would usher in a paradigm shift — from treating each age-related medical condition separately, to treating these conditions together, by targeting aging itself.”