Could metformin, the decades-old, generic medication used to treat type 2 diabetes, also be used to slow down biological aging?
The Targeting Aging with Metformin (TAME) trial, led by the nonprofit American Federation for Aging Research (AFAR), aims to answer this crucial question.
The nationwide, multi-center trial will span 14 leading research institutions across the U.S. and follow 3,000 participants, ages 65 to 79, who do not have diabetes.
Conducted as a double-blind, randomized, placebo-controlled trial, half of the participants will receive a standard daily dose of metformin at 1,500 mg/day, while the remaining will receive a matching placebo.
The trial, if it manages to secure funding, will take 6 years in total, with “aging” or multi-disease delay as its main goal. It is important to note that using metformin for longevity is off-label and not FDA-approved for anti-aging.
The review paper on the trial and metformin’s longevity potential on a wider scale appears in the journal Aging.
Medical News Todayspoke to two experts — David Cutler, MD, board-certified family medicine physician at Providence Saint John’s Health Center in Santa Monica, CA, and Diogo Barardo, PhD, longevity scientist and director of R&D at NOVOS — to discuss metformin’s potential in our pursuit of understanding human longevity.
As a first-line treatment for type 2 diabetes, metformin is a safe, low-cost drug. It works by improving insulin sensitivity, reducing glucose production in the liver, and activating the AMP-activated protein kinase (AMPK) cellular pathway, which helps regulate energy balance, sugar, and fat metabolism.
A 2024 study, published in the journal Cell by researchers from the Chinese Academy of Sciences, found that metformin decelerated aging in male monkeys’ brains by approximately 6 years over a 40-month treatment period.
Potential mechanisms by which metformin could promote longevity include:
“Metformin acts on a biochemical and cellular level to alter mitochondrial function, inflammation, insulin action, and epigenetic factors to alter basic cell physiology. These mechanisms could, in theory, have profound anti-aging effects,” Cutler said.
When asked how metformin can potentially slow aging, Barardo explained as follows: “Metformin appears to influence several interconnected systems involved in aging, especially nutrient sensing, cellular maintenance, and inflammatory signaling.”
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“One proposed route involves AMPK, a cellular energy sensor, and mTOR, which helps regulate growth and protein production. In experimental settings, metformin can activate AMPK and reduce mTOR signaling, potentially favoring maintenance processes such as autophagy—the recycling of cellular components,” he told MNT.
“Human trials also show changes in gut bacteria and some of their metabolites. These are plausible contributors to its wider effects, but neither finding establishes a longevity benefit,” he pointed out.
However, despite this potential, Cutler said the current evidence on metformin’s potential longevity benefits was mainly observational or from animal models such as worms and mice.
“There is a plausible and increasingly interesting case that metformin may slow some aspects of biological aging, but the evidence is not yet strong enough to say that metformin extends human life span,” he said.
“Changing a pathway involved in aging is not the same as proving that a treatment slows aging in a person,” Barardo chimed in.
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Cutler said stronger evidence is needed before this medication is seen as a viable longevity-enhancing drug for the general public. However, he singled out a specific group of people for whom studies have shown metformin can be beneficial.
“[In] diabetics who take metformin, there is good evidence of improved age-related measures like heart attacks, strokes, heart failure, and death. But whether this is due to the diabetes-controlling properties of metformin or its presumed anti-aging properties is not clear,” he said.
Cutler said more comprehensive studies are needed to confirm these findings for wider populations.
“The studies would need to be prospective, identifying participants first rather than looking back after the findings are known. Participants should be randomized, rather than simply comparing those who take the drug to those who don’t,” he continued.
“Ideally, studies should be placebo-controlled; half on metformin and half on a known useless pill. And the studies should be blinded, in that neither the participants for the scientists know if they are taking the metformin drug or an inert placebo (double-blinded),” he said.
Currently, medical experts do not recommend metformin for healthy individuals for longevity and warn against self-prescribing. Cutler said it is too premature to recommend that everyone use metformin for its purported longevity benefits.
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“Metformin has been used for diabetes for almost a hundred years. It is generally safe, well-tolerated, cheap, and effective for treating diabetes and preventing diabetic complications. However, due to its known risks and the unknown benefits in those without diabetes, it is not advisable for healthy people to take metformin for the purpose of improved longevity,” he warned.
“I would not recommend that an otherwise healthy person start metformin solely for longevity outside a clinical trial. That is different from its use for diabetes or for diabetes prevention in selected high-risk people. Someone already taking it for a medical indication should not stop because the longevity question remains unsettled,” Barardo said.
“For healthy people, my main concern is not that metformin is unusually toxic. It is that even a generally safe medicine needs to show enough benefit to justify taking it for years,” he added.
Cutler underscored that, as with all drugs, metformin can also have harmful effects.
“The negative effects include common GI side effects like nausea and diarrhea. Less commonly, but more seriously, is the occurrence of vitamin B12 deficiency caused by metformin. This can lead to anemia, neuropathy and even cognitive decline,” he said.
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“Very rarely, a serious condition called lactic acidosis can be caused by metformin,” he continued, adding that people with significant kidney or liver dysfunction are not advised to use metformin.
Instead of buying into the hype of longevity drugs, Cutler recommended the following scientifically-proven measures to help extend life and health span:
“My priorities would be regular aerobic activity and strength training, not smoking, a nutritious dietary pattern, sufficient sleep, and appropriate management of blood pressure, cholesterol, and blood glucose,” Barardo said.
“For most adults, the WHO recommends 150–300 minutes of moderate-intensity activity, or 75–150 minutes of vigorous activity, each week, alongside muscle-strengthening activity on at least two days. The starting point should be adapted to the person’s health and abilities,” he continued.
“Given all these safe and effective ways to improve longevity, it seems foolish to experiment with a drug which may have adverse effects and no proof of longevity effectiveness,” Cutler added.
