Metformin's promise in prolonging health
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Exploring Metformin's potential: the quest to extend healthspan and combat aging
A potentially affordable medication might be the key to slowing the aging process. Ongoing research and an upcoming study aim to verify whether metformin, a common diabetes medication, extends beyond its primary function of lowering blood glucose levels to possibly enhancing longevity and warding off age-related illnesses.
Metformin has shown promising signs of having anti-inflammatory properties, which could shield against several aging-related conditions such as heart disease, cancer, and cognitive impairments. In an effort to explore this possibility further, researchers in the field of aging biology have initiated a clinical study called The TAME Trial. This study will examine if metformin can indeed prevent these diseases and extend a healthier lifespan in older adults who are otherwise healthy.
Michael Cantor, a lawyer, alongside his wife, Shari Cantor, the mayor of West Hartford, Connecticut, both advocate for metformin, having experienced its benefits firsthand. "I tell all my friends about it," Michael says. He started using metformin roughly ten years ago when his weight and blood sugar levels began to rise. Shari joined him in taking the medication during the pandemic after learning about its potential protective benefits against severe infections. Now in their mid-60s, the couple reports feeling vibrant and energetic, noting particularly improvements in their digestive health since starting the medication.
Costing less than a dollar a day, metformin is highly affordable, with many insurance plans covering the full cost, leaving no out-of-pocket expense for the patient.
"The existing evidence, while not conclusive, suggests metformin could potentially increase lifespan," notes Steven Austad, a senior scientific advisor at the American Federation for Aging Research who is deeply involved in studying aging. Metformin, originally a derivative of guanidine found in the traditional European herbal medicine known as Goat's Rue, has been treating diabetes since the 1950s in France and was approved in the U.S. for treating type 2 diabetes in the 1990s.
Unexpectedly, research over the years has revealed that metformin users might have a lower incidence of certain cancers. "That was quite unexpected," Austad remarks, referencing a meta-analysis that indicated reduced risks of gastrointestinal, urologic, and blood cancers among metformin users. Further studies have linked metformin with lower rates of dementia and mild cognitive decline in diabetic patients, as well as improved cardiovascular outcomes, including a decreased risk of cardiovascular mortality.
However, Austad cautions that most findings to date are observational and only suggest a correlation rather than a definitive causal relationship. It remains uncertain whether these benefits can also apply to reducing the risk of age-related diseases in healthy, older adults.
"This is precisely what we hope to discover," says Steve Kritchevsky, a gerontology professor at Wake Forest School of Medicine and a principal investigator for the TAME Trial. The trial aims to delve deeper into how metformin influences the body, such as enhancing cellular energy through autophagy—the process by which cells cleanse themselves of damaged components—and reducing inflammation and oxidative stress, potentially decelerating the biological aging process.
Kritchevsky explains, "Aging occurs when cellular damage outpaces the body’s ability to repair and replace those cells." By targeting these underlying biological processes, researchers hope that metformin could slow aging and consequently delay the onset of multiple age-related diseases.
Leading the charge to commence the trial is Dr. Nir Barzilai from the Albert Einstein College of Medicine, who underscores the broader goal: to harness the biology of aging to stave off or delay various diseases, effectively altering the way we age.
Pioneering Metformin trial seeks to redefine aging as preventable, awaits critical funding
In 2015, Steven Austad and a team of researchers dedicated to the study of aging approached the FDA with a groundbreaking proposition: to conduct a clinical trial on metformin, believing it might be the pinnacle of preventative medicine. The FDA showed an openness to the idea, intrigued by the potential of metformin to concurrently prevent multiple age-related issues. "If you could help prevent multiple problems at the same time, like we think metformin may do, then that's almost the ultimate in preventative medicine," Austad stated.
The proposed trial, aimed at recruiting 3,000 individuals aged between 65 and 79 over six years, however, has faced financial hurdles. Dr. Nir Barzilai, who is spearheading this effort, notes the difficulty in securing funding primarily because metformin is a generic drug, which means it lacks the financial allure for pharmaceutical companies to invest in such extensive research.
Despite these challenges, there has been some progress with funding; philanthropic pledges and a $5 million commitment from the National Institute on Aging have been secured, though this falls significantly short of the estimated $45 to $70 million required to fund the study fully. Barzilai remains optimistic about the universal benefits if the trial confirms metformin's protective effects, emphasizing its affordability and potential widespread availability.
Another significant barrier is the FDA's current stance that does not recognize aging as a treatable condition. This trial could catalyze a shift in medical paradigms—from treating individual age-related diseases separately to addressing them collectively by targeting the aging process itself.
Presently, metformin is approved in the U.S. for treating type 2 diabetes, but it is also prescribed off-label for other conditions, a practice supported by its well-documented safety profile and potential health benefits. Both Michael and Shari Cantor, who are not diabetic, have been taking metformin under their doctors' guidance and report enhanced energy levels and no adverse effects.
While the benefits of metformin are promising, it is not without its challenges. A minority of users experience gastrointestinal distress, and some older individuals may face difficulties in muscle building due to a potential reduction in muscle mass gains associated with the drug, as noted by Dr. Eric Verdin, President of the Buck Institute for Research on Aging. Moreover, some metformin users may develop a Vitamin B12 deficiency, particularly those over the age of 65.
Verdin highlights ongoing research that explores metformin in combination with other drugs. One such study investigates the potential of metformin and galantamine to treat sarcopenia—a condition denoting age-related muscle loss that predominantly affects older women and millions globally.
The exploration of drugs targeting the biology of aging is expanding rapidly. Austad underscores that while metformin is a promising candidate, it may not be the ultimate solution. Insights gained from the clinical trial could stimulate greater interest and investment in this field, potentially leading pharmaceutical giants to develop even more effective therapies.
For individuals like Michael Cantor, who has a familial history of heart disease, the decision to use metformin is part of a broader strategy to enhance longevity and health. "Maybe it doesn't do what we think it does in terms of longevity, but it's certainly not going to do me any harm," he reflects.
As the research community awaits the necessary funding, the commencement of the metformin trial stands poised to potentially redefine approaches to aging and health maintenance, signaling a new era of therapeutic interventions.
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