Venka Stastny/Getty Images
Venka Stastny/Getty Images
The drugs millions of people take to control diabetes may do more than just lower blood sugar levels.
Research shows that metformin has anti-inflammatory properties and may help prevent common age-related diseases such as heart disease, cancer, and cognitive decline.
Scientists who study the biology of aging designed a clinical study known as the TAME trial to test whether metformin can help prevent these diseases and extend the health span of healthy older adults. Did.
Attorney Michael Cantor and his wife, Shari Cantor, the mayor of West Hartford, Conn., are both taking metformin. “I’ve been telling all my friends about this,” Michael Canter said. “We all want to live a higher quality of life, preferably a little longer,” he says.
Michael Canter started taking metformin about 10 years ago when his weight and blood sugar levels were slowly rising. Shari Canter started taking metformin after reading that it could help prevent serious infections during the pandemic.
Shari and Michael Canter are both taking metformin. Both are in their mid-60s and say they feel healthy and full of energy.
Theresa Oberst/Michael Canter
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Theresa Oberst/Michael Canter
Shari and Michael Canter are both taking metformin. Both are in their mid-60s and say they feel healthy and full of energy.
Theresa Oberst/Michael Canter
The Cantors are in their mid-60s and say they both feel healthy and full of energy. Both have noticed improvements in their digestive systems and feel more “regular” since starting the medication.
Metformin costs less than $1 a day, and depending on insurance, many people won’t pay a copay.
“We don’t know if metformin extends people’s lives, but the evidence that exists suggests that it is very likely,” said a senior at the American Federation for Research on Aging, which studies the biology of aging. Scientific advisor Steven Austad said.
Old medicine with surprising effects
Metformin was first used to treat diabetes in France in the 1950s. This drug is a derivative of guanidine, a compound found in Gautreux, a herbal medicine used for centuries in Europe.
The FDA approved metformin as a treatment for type 2 diabetes in the United States in the 1990s. Since then, researchers have documented some surprising things, including a reduced risk of cancer. “It was a bit of a shock,” Austad says. A meta-analysis that included data from dozens of studies found that people taking metformin had a lower risk of several types of cancer, including gastrointestinal, urinary, and blood cancers.
Professor Austad also pointed to a British study that found people with type 2 diabetes who took metformin had a lower risk of dementia and milder cognitive decline. Additionally, some studies point to improved cardiovascular disease outcomes (including reduced risk of cardiovascular death) in people taking metformin.
While this may sound promising, Austad says most of the evidence is observational and points only to an association between metformin and reduced risk. The evidence stops short of proving cause and effect. It is also unclear whether the benefits demonstrated in patients with diabetes also reduce the risk of age-related diseases in healthy older adults.
“That’s what we need to understand,” says Steve Krzyzewski, a professor of gerontology at Wake Forest School of Medicine and lead investigator on the TAME trial.
The goal is to better understand the mechanisms and pathways by which metformin acts in the body. For example, researchers are looking at how the drug helps improve energy within cells by stimulating autophagy, a process that removes or recycles damaged parts within cells. Masu.
Researchers also want to know how metformin helps reduce inflammation and oxidative stress, which may slow biological aging.
“Excessive oxidative stress damages cells, and the accumulation of that damage is essentially aging,” Krichevsky explains.
When the forces that damage cells are moving faster than the forces that repair or replace them, it’s aging, Krichevsky says. And drugs like metformin may slow this process.
Targeting the biology of aging holds promise for preventing or slowing multiple diseases, said Dr. Nir Barzilai of Albert Einstein College of Medicine, who is leading the effort to launch the trial.
ultimate preventive medicine
Back in 2015, Austad and older researchers began pushing for clinical trials.
“Some of us went to the FDA to ask them to approve a trial of metformin,” Austad recalls, and the FDA was happy to oblige. It’s almost the ultimate preventive medicine,” Austad says.
The goal is to enroll 3,000 people between the ages of 65 and 79 into the six-year trial. But Dr Barzilai says funding has been delayed. “The main obstacle to funding this research is that metformin is a generic drug, so there are no pharmaceutical companies making a profit,” he says.
Barzilai is relying on philanthropists and foundations and has made several pledges. The National Institute on Aging, part of the National Institutes of Health, has set aside about $5 million for the study, but not enough to fund the study, which is estimated to cost between $45 million and $70 million.
The complaint about lack of funding is that millions of people could benefit if trials show protection. “It’s something that everyone can afford,” Barzilai says.
Currently, the FDA does not recognize aging as a disease to be treated, but researchers hope this will usher in a paradigm shift. This means that instead of treating each age-related condition individually, we will be treating these conditions together by targeting aging itself.
Currently, metformin is only approved in the United States to treat type 2 diabetes, but doctors can prescribe metformin off-label for conditions outside of its approved use.
Physicians Michael and Shari Canter felt comfortable prescribing the drug because of its long history of safety and its potential to slow age-related diseases.
“I walk and hike a lot. At 65 years old, I have a lot of energy,” says Michael Cantor. “I feel like the metformin is working,” he said, adding that he and Shari have not experienced any negative side effects.
Research shows that a small number of people taking metformin experience gastrointestinal problems that make them unable to tolerate the drug. Some people also develop vitamin B12 deficiency. One study found that people over 65 may have a harder time building new muscle when they take metformin.
“There is some evidence that people who take metformin gain less muscle mass when they exercise, which is a concern for people who are lacking muscle,” said Dr. Eric Burdin, director of the Buck Institute on Aging. It may be a matter of concern.”
But Berdin said metformin could be repurposed in other ways: “There are a number of companies investigating combinations of metformin with other drugs.” He noted that research is underway to combine metformin with a drug called galantamine to treat sarcopenia, the medical term for age-related muscle loss. Sarcopenia affects millions of older adults, especially women.
The science of testing drugs that target aging is rapidly evolving, and metformin is not the only drug that has the potential to treat the underlying biology.
“No one thinks this is the be-all and end-all for drugs that target aging,” Austad says. He said data from clinical trials could spur investment in the area by major pharmaceutical companies. “They might invent better drugs,” he says.
Michael Canter knows there are no guarantees with metformin. “It may not be as effective as we think in terms of longevity, but it’s definitely not going to harm me,” he says.
Cantor’s father suffered his first heart attack at age 51. Cantor said he wants to do everything he can to prevent disease and live a healthy life, and he thinks metformin is one tool that could help with that. It is said that there is.
For now, Dr. Barzilai says clinical trials of metformin can begin once funding is raised.
This article was edited by Jane Greenhalgh
