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This Diabetes Drug Might Help Us All Live Longer

Studies suggest metformin’s powers go far beyond treating diabetes.
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Fast Facts

  • Studies suggest that metformin slows aging in animals and reduces aging-related diseases.
  • Clinical trials are currently examining whether metformin may delay the development or progression of some age-related chronic diseases in humans.
  • The mechanisms by which metformin works are still largely unknown.

Many researchers have puzzled over which behaviors, foods, and therapies can help us live longer. Potential answers include a rich social life, red wine, exercise, and diet. But there’s a newcomer on the longevity research scene: a common diabetes drug. But can—and should—you take metformin for anti-aging?

In recent years, that very question has been studied by scientists and doctors with some promising evidence.

“Poor lifestyle, food choices, and excess glucose can cause damage to our DNA, endothelial cells, and mitochondria,” says integrative physician Eric Acebedo, M.D. “That can lead to a shorter lifespan because of inflammation, which can contribute to heart attack, stroke, cancer, Alzheimer’s disease, and more.”

Clinical trials, including The Targeting Aging with Metformin (TAME) Trial, (1) a series of clinical trials at 14 different research centers in the U.S., are examining whether metformin may delay the development or progression of these age-related chronic diseases.

Results from animal models, large observational studies, and small human clinical trials like the Metformin In Longevity Study (MILES), suggests that “via its ability to reduce early mortality associated with various diseases, including diabetes, cardiovascular disease, cognitive decline and cancer, metformin can improve healthspan thereby extending the period of life spent in good health” (2).

Of course, there are still many unknowns as it relates to metformin and aging — particularly when taken by otherwise healthy individuals. Here’s what researchers currently know about metformin and anti-aging, and what they’re studying next.

What is Metformin?

Metformin belongs to a class of medications called biguanides (3). The drug is the most commonly prescribed medication for the treatment of type 2 diabetes, a health condition that occurs when your body doesn’t use insulin properly.

Insulin is a hormone that controls the amount of glucose in your blood; metformin lowers the amount of sugar the body absorbs and produces.

Metformin is already used off-label to treat obesity, cancer, and heart disease, says Acebdeo. Emerging research suggests that in healthy people it may also help with weight loss, inflammation, and cancer prevention.

Data from animal studies suggests that metformin may also delay the effects of aging or increase lifespan (4). Currently, large clinical trials involving people are being planned to determine, which, if any, anti-aging benefits may extend to humans.

Metformin at a Glance

  • Metformin lowers the amount of sugar the body absorbs and produces.
  • Metformin is used off-label to treat obesity, cancer, and heart disease.
  • Data from animal studies suggests that metformin may also delay the effects of aging or increase lifespan.

How Might Metformin Work for Anti-Aging?

While the research on metformin for anti-aging is limited, studies (5) suggest that the drug slows aging in animals and “reduces the incidence of aging-related diseases such as neurodegenerative disease and cancer in humans.” But the mechanisms by which it works are still—largely—question marks.

“Glucose is damaging to the mitochondria and produces oxidative stress,” Acebedo says. Oxidative stress is an imbalance between free radicals—molecules that can cause large chain chemical reactions in your body—and antioxidants in your body.

Some researchers suspect that metformin may activate an enzyme called telomerase, which lengthens telomeres and helps protect your chromosomes from degradation. “Telomeres are the end of the chromosomes; they’re like a cap that protects your chromosomes,” explains Acebedo.

Telomeres also shorten each time the DNA replicates and shortened telomeres are linked with aging, poor health, cognitive dysfunction, cancer, stress, and more. One recent study published in Aging and Disease (6) confirmed as much, with authors stating, “collectively, metformin could delay the aging process by maintaining telomere length.”

There are many ways to protect telomere health, including exercise and a healthy diet (7), specifically, diets such as intermittent fasting and fasting-mimicking diets, says Acebedo.

Autophagy—the body’s way of destroying damaged cells—may also explain metformin’s potential role in anti-aging, says Acebedo. Metformin could induce autophagy by way of signaling pathways related to AMPK, an enzyme that plays a role in stimulating glucose uptake in the body (8). “It improves the insulin sensitivity of the cells,” he says.

Animal studies suggest that metformin might delay the effects of aging or increase lifespan by improving the body’s responsiveness to insulin, improving blood vessel health, and having antioxidant effects (4).

Currently, large clinical trials involving people are being planned (9) to determine which, if any, anti-aging benefits that they’ve seen in animal studies apply to people.

Metformin for Anti-Aging

  • Metformin’s potential to ward off age-related diseases may be tied to its ability maintain telomere length.
  • Shortened telomeres are linked with aging, poor health, cancer, and stress. 
  • Metformin may also improve the body’s response to insulin.

Metformin and Age-Related Illness

Research suggests that metformin may reduce the risk for several age-related conditions.

Cancer

Studies have shown that metformin can reduce the risk and mortality of cancer and improve the efficacy of cancer treatment in diabetic patients (10). Patients with untreated diabetes have a higher risk for cancer, and taking metformin reduced their risk of cancer to near non-diabetic levels, with the strongest effects seen with pancreatic, liver, and colon cancers (11).

Some research suggests that metformin down-regulates certain genes that are activated in cancer parents, says Acebedo.

Research about reducing cancer risk and severity in people without diabetes is limited, but shows some promise in certain patients, and is the subject of clinical trials (10).

Heart disease

One meta-analysis of 204 studies (12) involving more than 1.4 million people with diabetes suggests that metformin reduces the relative risk of a patient dying from heart disease by about 30 to 40 percent compared to its closest competitor drug.

Some evidence also suggests that the drug is a potential treatment for heart disease in those without diabetes (13).

 

Cognitive decline

Long-term use of metformin has been linked to a reduced risk of cognitive impairment in people with diabetes (14). Other research has found that older people with type 2 diabetes who take metformin have slower cognitive decline and lower dementia risk (15).

Obesity

Many people with type 2 diabetes have lost weight after taking metformin. Metformin also helps induce a hypocaloric state in the body (which is when you’re low on calories) by inhibiting a pathway by which fat is formed, Acebedo says. Independently, microbiome stimulation could also aid in weight loss, he says.

Insulin-resistant and diabetic patients can expect about 6 pounds of weight loss over about a year’s time (16), but some people may lose more, says Acebedo. If you’re not diabetic, the impact will be limited. You might lose two or three pounds over three months, Acebedo says.

Inflammation

Recent studies show that metformin improves chronic inflammation by improving metabolic parameters such as insulin resistance and by modulating the gut microbiome. It also has a direct anti-inflammatory effect (9).

Metformin and Age-Related Illnesses

  • Studies have shown that metformin can reduce the risk and mortality of cancer.
  • Long-term use of metformin has been linked to a reduced risk of heart disease and cognitive impairment in people with diabetes
  • Many people with type 2 diabetes have lost weight after taking metformin. Obesity has been linked to many age-related diseases.
Research suggests that metformin may reduce the risk for several age-related conditions.

Metformin and Looking Younger

Metformin may help your skin look younger, especially if you have pre-diabetes or diabetes, notes Acebedo. Some people with diabetes experience skin thickening or discoloration. Metformin can counter this build-up of skin by improving insulin sensitivity in skin cells and lowering levels of a hormone called insulin-like growth factor 1 (IGF-1R), which is associated with skin wrinkling (17).

People with diabetes also tend to look older than their biological age, in part because excess blood sugar negatively impacts skin proteins called collagen. Over time, with metformin use, the skin will start to look younger, Acebedo says.

Who Can Take Metformin

Currently, metformin is FDA-approved for treating type 2 diabetes. The National Institutes of Health’s National Library of Medicine notes that metformin may be prescribed off-label for other reasons beyond type 2 diabetes. Among them:

  • Prediabetes
  • Cancer
  • Liver disease
  • Cardiovascular disease
  • Obesity
 

If you’re interested in taking metformin for anti-aging, speak to your physician.

Side Effects

Since metformin causes changes in blood sugar, The National Institutes of Health’s National Library of Medicine notes that it’s important to know the symptoms of both high and low blood sugar. Additionally, you could notice some of the below symptoms while taking metformin:

  • Gastrointestinal (GI) symptoms such as diarrhea, bloating, gas, constipation, or stomach pain
  • A metallic taste in your mouth
  • Heartburn
  • Headache
  • Skin or nail changes
  • Muscle pain
 

There’s also a possibility that metformin could hinder your fitness goals. One recent study published in Aging Cell found that elderly participants who took metformin didn’t gain as much benefit from aerobic exercise as those taking a placebo pill over the course of a 12 week trial (18). Researchers found that the drug blocked the gains in mitochondrial health that the excercisers would otherwise get from their workout. Having healthy mitochondria is key to aging well.

Another study on elderly adults participating in resistance training showed a blunting effect on adding lean body and muscle mass when taking metformin (19). In both trials, the sample sizes were small and the effects were variable between participants, highlighting the need for more studies.

Benjamin Miller, Ph.D., a principal investigator in the aging and metabolism research program at the Oklahoma Medical Research Foundation, who oversaw the Aging Cell study told the New York Times that the results of that study don’t mean that people should avoid the drug, even if they’re taking it for the potential anti-aging benefits. But the findings “do give us reason to think a bit more cautiously” about the impact of metformin on exercise in healthy people, Miller told the Times.

The Bottom Line

Preliminary research suggests that metformin could be a powerful tool in fighting aging and a slew of degenerative diseases from cancer to inflammation, but more research needs to be done, particularly on the potential benefits in healthy people. If you are interested in trying metformin for the potential anti-aging benefits, talk to your physician.
1. Targeting Aging with Metformin (TAME) Trial, afar.org
Mohammed Ibrahim, et al (2021), A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan, 
2. Bailey CJ (2017). Metformin: historical overview. 
3. Wang, Yi-Wei et al (2017). Metformin: a review of its potential indications. 
4. Soukas AA, Hao H, Wu L (2019). Metformin as Anti-Aging Therapy: Is It for Everyone? 
5. Hu D, Xie F, Xiao Y, et al (2021). Metformin: A Potential Candidate for Targeting Aging Mechanisms. 
6. Balan E, Decottignies A, Deldicque L (2018). Physical Activity and Nutrition: Two Promising Strategies for Telomere Maintenance?. 
7. Lu G, et al (2021). The effects of metformin on autophagy. 
8. Kulkarni AS, et al (2020). Benefits of Metformin in Attenuating the Hallmarks of Aging. 
9. Chen K, et al (2020) Metformin: current clinical applications in nondiabetic patients with cancer. 
10. Lee, MS., Hsu, CC., Wahlqvist, M.L. et al (2011). Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals. 
11. Maruthur NM, et al (2016). Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis. 
12. Rena G, Lang CC (2018). Repurposing Metformin for Cardiovascular Disease. Circulation. 
13. Ng TP, et al (2014) Long-term metformin usage and cognitive function among older adults with diabetes. 
14. Teng Zhenjie,et al (2021) Long-Term Use of Metformin Is Associated With Reduced Risk of Cognitive Impairment With Alleviation of Cerebral Small Vessel Disease Burden in Patients With Type 2 Diabetes. 
15. Diabetes Prevention Program Research Group (2012). Long-term safety, tolerability, and weight loss associated with metformin in the Diabetes Prevention Program Outcomes Study. 
16. Noordam R, et al (2013). Serum insulin-like growth factor 1 and facial ageing: high levels associate with reduced skin wrinkling in a cross-sectional study. 
17. Konopka AR, et al (2019). Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults 
18. Walton RG, et al (2019). Metformin blunts muscle hypertrophy in response to progressive resistance exercise training in older adults: A randomized, double-blind, placebo-controlled, multicenter trial: The MASTERS trial. 

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