Millions of individuals are prescribed Metformin to manage diabetes, but emerging research suggests it may offer benefits beyond blood sugar control. The TAME (Targeting Aging with Metformin) Trial, a clinical study led by scientists studying the biology of aging, will explore whether metformin can prevent age-related diseases and promote a longer healthspan in healthy, older adults.
Surprising Benefits of an Old Drug
Metformin, derived from guanidine found in Goat's Rue, was first used to treat diabetes in France in the 1950s. Approved by the FDA for type 2 diabetes in the U.S. in the 1990s, it has since been linked to a reduced risk of cancer. A meta-analysis showed that metformin users had a lower risk of gastrointestinal, urologic, and blood cancers. Steven Austad, a senior scientific advisor at the American Federation for Aging Research, also highlights a British study indicating a lower risk of dementia and mild cognitive decline among people with type 2 diabetes taking metformin, as well as research pointing to improved cardiovascular outcomes.
Understanding Metformin's Mechanisms
Steve Kritchevsky, a professor of gerontology at Wake Forest School of Medicine and a lead investigator for the TAME Trial, emphasizes the need to understand how metformin works in the body. Researchers are investigating how the drug improves cellular energy by stimulating autophagy, the process of clearing out damaged components inside cells. They also aim to understand how metformin reduces inflammation and oxidative stress, potentially slowing biological aging.
"When there's an excess of oxidative stress, it will damage the cell. And that accumulation of damage is essentially what aging is," Kritchevsky explains. The trial seeks to determine if metformin can slow down the aging process by targeting the underlying biology.
The TAME Trial: Design and Funding
The TAME Trial aims to enroll 3,000 individuals aged 65 to 79 for a six-year study. Nir Barzilai of Albert Einstein College of Medicine, who leads the effort to initiate the trial, notes that funding has been a challenge due to metformin's generic status. The trial is estimated to cost between $45 and $70 million. While the National Institute on Aging has allocated approximately $5 million, additional funding from philanthropists and foundations is crucial.
Potential Implications and Future Directions
If the trial demonstrates protective effects, millions could benefit from this affordable drug. Currently, the FDA does not recognize aging as a treatable disease, but researchers hope this trial could shift the paradigm toward targeting aging itself to prevent multiple age-related conditions simultaneously.
Eric Verdin, President of the Buck Institute for Research on Aging, notes that some studies suggest metformin may hinder muscle gain in older adults who exercise and that a small percentage of people who take metformin experience GI distress or a b12 vitamin deficiency. However, he also points to ongoing research exploring metformin in combination with other drugs, such as galantamine for sarcopenia, the medical term for age-related muscle loss.
Austad emphasizes that metformin is not the only potential drug for targeting aging and that the TAME Trial's data could stimulate investment from pharmaceutical companies in developing even better drugs.
