Content Library Articles Longevity Journal

Metformin and Longevity: Promising Science or Overhyped Solution?

December 9, 2024

Imagine this: a pill that could slow aging, reduce your risk of chronic disease, and extend your lifespan.

That’s the promise of metformin, a diabetes drug now being hailed as a potential longevity breakthrough. Scientists point to its ability to mimic fasting, activate cellular repair, lower inflammation, and improve metabolic health—drawing excitement from researchers and biohackers alike.

It’s an intriguing idea. But here’s the thing: Metformin’s effects aren’t as unique as they might seem.

Much of what this drug promises can also be achieved through lifestyle interventions like exercise, fasting, and dietary changes.

While the science behind metformin is promising, there are still unanswered questions, especially for healthy individuals. 

So, is metformin the key to longer, healthier lives, or does its appeal distract from proven ways to support aging well? 

Let’s dive into the science and find out.

How Metformin Works

Metformin has been a go-to treatment for Type 2 diabetes for decades because it lowers blood sugar safely and effectively. 

It works by reducing the amount of glucose your liver produces and helping your cells respond better to insulin. Together, these actions keep your blood sugar stable and in check.

But metformin’s benefits might not stop at blood sugar control. 

Over the years, researchers began noticing something unexpected: People with diabetes who took metformin seemed to live longer than folks with diabetes who didn’t take the drug In some cases, they even appeared to outlive people without diabetes.¹ 

This surprising trend sparked a wave of interest in metformin as a potential longevity drug. 

Could Metformin Slow the Aging Process? 

The excitement around metformin as a longevity drug comes from its ability to influence the very processes that drive aging. Researchers have uncovered several ways this diabetes medication might extend lifespan and reduce the risk of chronic diseases. 

► Mechanism #1: It activates your “longevity switch”

One of metformin’s most talked-about effects is its activation of AMPK (short for adenosine monophosphate (AMP)-activated protein kinase). AMPK is often referred to as a “longevity switch.” 

AMPK is a key enzyme that tells your cells when to save energy and focus on repair. (Enzymes are proteins that help chemical reactions happen in your cells.) When AMPK is activated, your cells shift gears—clearing out damaged parts, recycling old components, and reducing inflammation. This process helps your cells work better and stay healthier for longer.
(Exercise and fasting are also powerful ways to activate AMPK, triggering these repair processes naturally.)

Why this matters for aging: Chronic inflammation and cellular wear-and-tear are major drivers of age-related diseases. Boosting AMPK helps protect your cells and keeps them functioning longer.

► Mechanism #2: It mimics the effects of fasting

Metformin is often compared to fasting because it triggers many of the same cellular responses. Both lower insulin levels, reduce blood sugar, and activate protective pathways that help cells withstand stress.

Why this matters for aging: Fasting has been shown to extend lifespan in animal studies. Metformin may offer similar benefits, which is why it’s sometimes called a “fasting mimetic.”² 

(It’s important to note that fasting itself offers the same benefits without medication, and even short periods of time-restricted eating have been shown to lower insulin and improve metabolic health.)

► Mechanism #3: It reduces oxidative stress

Your mitochondria—tiny power plants in your cells—generate energy, but they also produce harmful byproducts called reactive oxygen species (ROS). Metformin helps your mitochondria work more efficiently, reducing the amount of ROS they create.

Why this matters for aging: Less oxidative stress means less damage to your DNA and proteins, both of which are crucial for keeping cells healthy as you age.

Promises, Pitfalls, and Unanswered Questions

While the evidence surrounding metformin and longevity is promising, it’s far from conclusive. Metformin seems to work well in individuals with insulin resistance or metabolic dysfunction. But there are still many unanswered questions—especially when it comes to how metformin works in people without diabetes. 

And here, the picture gets murkier. 

For example, some studies suggest that metformin might blunt the benefits of exercise, particularly when it comes to building muscle and improving mitochondrial function. For active individuals, this trade-off could make metformin less appealing as a longevity tool. 

► Trade-off #1: Metformin may limit muscle growth during strength training 

A study of adults aged 65+ found that metformin blunted the muscle gains typically seen with resistance training.³

Participants who took metformin for 14 weeks gained significantly less muscle mass and density compared to those on a placebo. While both groups improved in strength, the metformin group’s gains were smaller (and not statistically significant).

► Issue #2: Metformin may block some benefits of aerobic exercise 

In a study of adults aged 62+, researchers found that taking metformin during a 12-week aerobic exercise program reduced key fitness and health improvements.⁴

While all participants lowered their blood sugar levels and fat mass, those taking metformin saw smaller gains in insulin sensitivity and aerobic fitness (VO2max). Metformin also prevented improvements in mitochondrial respiration, a critical process for energy production in muscle cells.

The researchers concluded that although metformin offers many health benefits, it might counteract some positive effects of exercise, especially in older adults trying to improve fitness and metabolic health.

And there’s more.

► Issue #3: It can cause kidney strain in some people 

In frail or elderly populations, the risks linked to metformin become increasingly complex. While it’s generally considered safe, metformin can occasionally cause complications. One of the more serious—but rare—risks is lactic acidosis, a potentially life-threatening condition, where lactic acid builds up in the blood faster than it can be cleared.⁵

This can disrupt your body’s pH balance and, in severe cases, lead to organ dysfunction. People with impaired kidney function are particularly vulnerable because their kidneys play a key role in clearing lactic acid from the bloodstream. When the kidneys are already strained, metformin may further increase the risk of lactic acidosis, creating a dangerous cycle.

All of these risks may be acceptable for someone managing a condition like diabetes, but they’re harder to justify when the goal is longevity alone—especially in individuals with underlying health issues.

The Big Takeaways

1. 1. More research is needed. A six-year clinical trial known as TAME— Targeting Aging with Metformin —is set to test whether metformin can delay the onset of age-related diseases like cancer, heart disease, and dementia in healthy older adults. Sponsored by the NIH and coordinated by Wake Forest University, the trial is still in its preparation stage but holds promise for providing much-needed clarity.
   
   
2. 2. The risks outweigh the benefits for longevity use. Based on what we know now, the potential risks of metformin make it an unfavorable choice for healthy individuals looking to extend their lifespan.
   
   
3. 3. Lifestyle remains the foundation of good health. As exciting as new therapies can be, the core of longevity lies in the basics: eating whole, nutrient-dense foods, engaging in regular strength and cardio training, and prioritizing quality sleep. These practices naturally activate the same pathways we’re targeting with drugs like metformin, reducing inflammation, improving energy metabolism, and repairing cells.

References

1. Bannister CA, Holden SE, Jenkins-Jones S, Morgan CL, Halcox JP, Schernthaner G, Mukherjee J, Currie CJ. Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls. Diabetes Obes Metab. 2014 Nov;16(11):1165-73. doi: 10.1111/dom.12354. Epub 2014 Jul 31. PMID: 25041462. 
   
   
2. Stojić V, Štrbac T, Stanimirović A. New anti-aging strategies: a narrative review. Acta Dermatovenerol Alp Pannonica Adriat. 2023 Dec;32(4):159-164. PMID: 38126098.
    
3. Walton RG, Dungan CM, Long DE, Tuggle SC, Kosmac K, Peck BD, Bush HM, Villasante Tezanos AG, McGwin G, Windham ST, Ovalle F, Bamman MM, Kern PA, Peterson CA. 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. Aging Cell. 2019 Dec;18(6):e13039. doi: 10.1111/acel.13039. Epub 2019 Sep 26. Erratum in: Aging Cell. 2020 Mar;19(3):e13098. doi: 10.1111/acel.13098. PMID: 31557380; PMCID: PMC6826125.
   
   
4. Konopka AR, Laurin JL, Schoenberg HM, Reid JJ, Castor WM, Wolff CA, Musci RV, Safairad OD, Linden MA, Biela LM, Bailey SM, Hamilton KL, Miller BF. Metformin inhibits mitochondrial adaptations to aerobic exercise training in older adults. Aging Cell. 2019 Feb;18(1):e12880. doi: 10.1111/acel.12880. Epub 2018 Dec 11. PMID: 30548390; PMCID: PMC6351883. 
   
   
5. Brand KMG, Schlachter J, Foch C, Boutmy E. Quality and Characteristics of 4241 Case Reports of Lactic Acidosis in Metformin Users Reported to a Large Pharmacovigilance Database. Ther Clin Risk Manag. 2022 Nov 4;18:1037-1047. doi: 10.2147/TCRM.S372430. PMID: 36389204; PMCID: PMC9642855.