Metformin has been a reliable diabetes drug for decades, but now researchers are looking at a bigger question—can it slow aging? Some studies suggest that people taking metformin may live longer and stay healthier, and now a major clinical trial, the TAME study, is trying to find out if the drug could help non-diabetics too.
Why scientists are interested in metformin for aging
Metformin is one of the most commonly prescribed medications for type 2 diabetes, but its potential effects on aging weren’t something doctors originally set out to study. The interest started when researchers noticed that diabetics on metformin seemed to be living longer than expected—even outliving some non-diabetics. That’s unusual since diabetes is normally associated with shorter lifespan and a higher risk of age-related diseases.
That observation led to further research, and scientists found that metformin seemed to have effects beyond just controlling blood sugar. In laboratory studies, it extended lifespan in mice, worms, and even fruit flies. In humans, large observational studies suggested it might lower the risk of diseases like cancer, heart disease, and even Alzheimer’s.
The idea behind metformin as a longevity drug is that it affects several biological pathways linked to aging. It activates AMPK, an enzyme involved in metabolism and cellular energy balance. This is important because AMPK helps mimic the effects of calorie restriction—a well-known longevity intervention that has been shown to extend lifespan in multiple species. Metformin also reduces inflammation, which is a key driver of aging, and may improve mitochondrial function, the part of the cell responsible for energy production.
The TAME trial and what it aims to prove
While observational studies suggest metformin users may live longer and healthier lives, those studies don’t prove cause and effect. It’s possible that people taking metformin for diabetes have other health habits that contribute to longevity. That’s why researchers launched the TAME trial (Targeting Aging with Metformin), a large-scale study designed to test whether metformin can slow aging in non-diabetics.
TAME is enrolling 3,000 older adults (ages 65–79) who do not have diabetes and tracking whether those taking metformin develop fewer age-related diseases over time. Instead of just looking at lifespan, the trial is focused on healthspan—the number of years people live in good health, free from major disease. Researchers will measure whether metformin users experience lower rates of heart disease, cancer, dementia, and other common aging-related conditions.
Unfortunately TAME has faced significant funding delays, primarily because metformin is a generic drug with little financial incentive for pharmaceutical companies to support large-scale studies. Initially planned as a six-year trial involving over 3,000 participants, it remains only partially funded, with an estimated cost of $45–$70 million. As of April 2024, the trial has not yet begun, meaning results are not expected anytime soon.
Other studies have already provided some clues about metformin’s potential anti-aging effects. The MILES trial (Metformin in Longevity Study) found that metformin altered gene expression in older adults, making their cells behave more like those of younger individuals. Another study is testing whether metformin can slow epigenetic aging, which refers to changes in DNA that accumulate over time and contribute to biological aging.
The potential benefits of metformin for longevity
If metformin does work as a longevity drug, the biggest benefit wouldn’t necessarily be extending lifespan—it would be extending healthspan. The idea is that metformin might help people stay healthier for longer by delaying the onset of age-related diseases.
Some of the possible benefits of metformin include:
- Delaying chronic diseases – Metformin could reduce the risk of cancer, heart disease, and cognitive decline, all of which increase with age.
- Extending healthspan – Instead of just living longer, people could remain active and independent for more years.
- Reducing inflammation – Chronic inflammation is a major contributor to aging, and metformin appears to counteract it.
- Improving metabolism – Even in non-diabetics, metformin has been shown to lower insulin levels and improve metabolic health.
- Mimicking calorie restriction – Research has long shown that calorie restriction extends lifespan in animals, and metformin might provide similar benefits.
If the TAME trial confirms these effects, metformin could become one of the first drugs approved specifically for aging prevention.
The limitations and trade-offs of metformin
Despite the excitement, metformin is not a guaranteed anti-aging solution. The longevity effects seen in animal studies have been modest—typically a 5–10% increase in lifespan at best. That’s meaningful, but it’s not a dramatic extension of life.
One big question is who benefits the most from metformin? Some scientists believe it’s most helpful for people with metabolic dysfunction—those who are overweight, insulin-resistant, or prediabetic. For individuals who are already fit and metabolically healthy, the benefits may be smaller.
Another concern is how metformin interacts with exercise. Some studies suggest that metformin may blunt some of the benefits of exercise, particularly muscle growth from strength training. This happens because metformin dampens inflammation, which is normally part of the muscle-building process. For older adults trying to maintain muscle mass, this could be a downside. Some longevity researchers, including Dr. David Sinclair, have suggested that people who work out regularly might want to take metformin on non-exercise days to avoid this effect.
Metformin also has some mild side effects. The most common are gastrointestinal issues like nausea and diarrhea, though these usually improve over time. A more serious concern is vitamin B12 deficiency, which can develop with long-term metformin use. People taking it for aging would likely need to monitor their B12 levels.
A rare but serious risk is lactic acidosis, though this is primarily seen in people with severe kidney disease. That’s why metformin is not recommended for people with advanced kidney problems.
The regulatory and ethical questions
One major barrier to metformin becoming a mainstream aging drug is the regulatory issue. The FDA does not consider aging a disease, which means drugs cannot be officially approved for aging prevention. That’s why the TAME trial is focused on preventing age-related diseases rather than aging itself.
If the trial is successful, it could lead to a shift in how aging is treated by the medical community. It could also set a precedent for approving other drugs that target aging at the biological level.
There are also ethical questions about whether aging should be treated like a disease. Some argue that extending healthspan is a public health priority, while others worry about over-medicalizing a natural process. If metformin works, should it be recommended for everyone over a certain age? Should insurance cover it? These are questions researchers and policymakers will need to answer.
Should you take metformin for longevity?
For now, metformin is not officially approved for aging prevention, but some doctors are prescribing it off-label for this purpose. A growing number of people are also self-experimenting with metformin, often obtaining it through online sources.
Whether it makes sense to take metformin now depends on individual health status. For those with prediabetes, insulin resistance, or metabolic syndrome, metformin may provide clear benefits. For very healthy individuals, the effects may be less obvious, and potential downsides like reduced exercise adaptation should be considered.
Our takeaway
Metformin is one of the most promising drugs being studied for aging prevention, but the research isn’t settled yet. Observational data and animal studies suggest it could help people live longer, healthier lives, but we need well-controlled clinical trials like TAME to confirm this.
If metformin does show real benefits, it could mark a shift in how aging is treated—not as an inevitable decline, but as something that can be managed like any other health condition. However, even if the effects are modest, a safe, cheap drug that helps people stay healthier for longer would still be an important tool in the fight against age-related disease.
For now, the best approach is to wait for the results of clinical trials. If metformin truly works as an anti-aging drug, it could be one of the first widely available treatments to help people stay healthier as they age.
Sources
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- Metformin regulates metabolic and nonmetabolic pathways in skeletal muscle and subcutaneous adipose tissues of older adults – PMC
- A cheap drug may slow down aging. A study will determine if it works | Health News Florida
- Frontiers | Repurposing effect of cardiovascular-metabolic drug to increase lifespan: a systematic review of animal studies and current clinical trial progress
- The Gehan test identifies life-extending compounds overlooked by …
- The Anti-Aging Mechanism of Metformin: From Molecular Insights to Clinical Applications
- Dr. Nir Barzilai—Genetics and Lifestyle Factors of Centenarians
- Metformin as Anti-Aging Therapy: Is It for Everyone? – PMC
- A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan – PubMed
- About TAME: A Metformin Anti-Aging Clinical Trial with Nir Barzilai, M.D. – Peter Attia
Marko is the founder and editor of LifeSpan Digest. With a deep interest in biotech, healthspan optimization, and regenerative medicine, he analyzes emerging discoveries and explores how science is reshaping human aging. Through expert insights and data-driven reporting, he provides readers with the knowledge to stay ahead in the rapidly evolving field of longevity.