Published March 21, 2019 · Updated July 7, 2026
Once hailed as a possible longevity and anti-cancer drug, metformin has a more precise story to tell. A wave of randomized trials — capped by a July 2026 analysis from Peter Attia’s research team — suggests it is neither a fountain of youth nor a broad shield against cancer, but may still matter in well-defined situations.
Metformin is sold under several trade names, including Glucophage XR, Carbophage SR, Riomet, Fortamet, Glumetza, Obimet, Gluformin, Dianben, Diabex, Diaformin, Siofor, Metfogamma and Glifor. The USDA cites it as a weed.
Although endless pharmacovigilance has monitored the safety profile of metformin, its natural ancestor, G. officinalis (known as Professor Weed in the USA) is a Class A Federal Noxious Weed in 35 states of America, and appears on the database of poisonous plants. (Wiley)
History
The discovery of metformin dates back to the 17th century. Galega officinalis L., also known as the French lilac, was used as a herbal remedy to relieve the intense urination caused by diabetes mellitus in medieval times [1]. The guanides are rich in French lilac and are essential compounds in lowering blood glucose, which led to the development of three biguanides: metformin, phenformin, and buformin. Among them, metformin was found to be the most useful drug because of its low toxicity. It was first synthesized in 1922, but not approved for the treatment of diabetes in Europe until the 1950s, and by the U.S. Food and Drug Administration (FDA) in 1994. It is on the World Health Organization’s List of Essential Medicines, the most effective and safe medicines needed in a health system.
Galega officinalis Linn was a herbal medicine in medieval Europe. G. officinalis (Leguminosae) is a perennial herb with white, blue or purple flowers that grows over three feet high and is found in most temperate regions, including Britain. Its common names include goat’s rue, French lilac, Spanish sanfoin and false indigo. Aerial parts of the plant were used medicinally in medieval Europe to treat plague, worms, snake bites, miasma, dysuria and St Vitus dance, and the plant was fed to livestock to increase milk yield.
Purpose
- Metformin is the first-line medication prescribed to over 150 million patients worldwide for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome (PCOS). Limited evidence suggests metformin may reduce the chances of certain forms of cancer arising from complications of diabetes.
- The molecular mechanism of metformin is incompletely understood. Multiple potential mechanisms of action have been proposed, including: inhibition of the mitochondrial respiratory chain (complex I), activation of AMP-activated protein kinase (AMPK), inhibition of glucagon-induced elevation of cyclic adenosine monophosphate (cAMP) with reduced activation of protein kinase A (PKA), inhibition of mitochondrial glycerophosphate dehydrogenase, and an effect on gut microbiota.
Why Supplement?
- Metformin’s main effect is to decrease liver glucose production. It also has an insulin-sensitizing effect with multiple actions on tissues including the liver, skeletal muscle, endothelium, adipose tissue, and the ovary.
- Metformin decreases high blood sugar, primarily by suppressing liver glucose production (hepatic gluconeogenesis).
That said, from various studies, 25–45% of humans are non-responders to metformin, and so may get only the side effects (see below).
Why Supplement for Longevity and Anti-Cancer Properties
Up until 2026, the following was believed to be true:
- A 2017 review and meta-analysis found that people with diabetes who were taking metformin had 7% lower all-cause mortality, and less cancer (breast, gastrointestinal, liver, pancreatic) than those on other therapies.
- Numerous observational studies reported an association between metformin use and a decreased risk of cancer, as well as decreased cancer mortality. Supporting mechanisms proposed from in-vitro and in-vivo work include reduced insulin levels, improved insulin action, decreased insulin-like growth factor 1 (IGF-1) signaling (central to mammalian longevity), reduced cellular senescence, and activation of AMPK.
- A 2014 large population-based study evaluated the effect of metformin on five-year survival. Records of 78,000 diabetic patients treated with metformin were compared with records of 78,000 non-diabetic subjects matched for age, smoking, cancer history and other characteristics. A parallel comparison was performed between 12,000 diabetic patients taking sulphonylurea (SU) drugs and 12,000 matched non-diabetic individuals. SU-treated diabetic patients had roughly 40% greater mortality than their non-diabetic control group. However, mortality in metformin-treated diabetic patients was similar to the matched non-diabetic controls, and among patients in their 70s was reduced by about 15% versus non-diabetic controls. These observations were used to argue that metformin’s protective action might extend beyond effects on specific age-related diseases, and helped motivate the push for a trial to test whether human aging and its diseases could be delayed.
Crucially, the observational cancer signal has not held up in randomized trials (see the new section below). The optimistic framing in this section reflects the pre-2022 consensus; treat it as historical context rather than settled fact.
Metformin and Cancer: From Broad Promise to Precision (2026)
For a decade, metformin was one of longevity medicine’s favorite “might-as-well” drugs: cheap, familiar, and seemingly linked in observational data to less cancer and longer life. A run of randomized controlled trials (RCTs) — summarized in a July 2026 analysis by Peter Attia and colleagues — has steadily narrowed that story. The headline: metformin is not a general-purpose anti-cancer or anti-aging drug, though a few specific signals survive.
The MAST trial: no benefit in low-risk prostate cancer
The Metformin Active Surveillance Trial (MAST) was a Phase III, randomized, double-blind, placebo-controlled trial run across 12 Canadian cancer centers. It enrolled 408 non-diabetic men with low-risk, localized prostate cancer who were on active surveillance — a “watch and monitor” approach that avoids immediate treatment. Men received either metformin (850 mg twice daily) or placebo for up to 36 months, with scheduled biopsies (Fleshner et al., Journal of Clinical Oncology, 2025).
After a median of three years, 144 of the 408 men’s cancers had progressed — 70 on metformin, 74 on placebo. There was no significant difference in progression-free survival between the groups (hazard ratio [HR] 1.09, 95% confidence interval [CI] 0.79–1.52; p=0.59). In plain terms: metformin did not delay progression of low-risk prostate cancer.
One subgroup finding cut the other way. In obese men (body mass index [BMI] ≥30) — the group most likely to be insulin-resistant, and therefore the group the “metformin fixes metabolism” theory predicts should benefit most — metformin was associated with increased progression (HR 2.36, 95% CI 1.21–4.59; p=0.0092), the opposite of the expected direction. Because this was one of several subgroup analyses, it may be a fluke rather than real biology, but it is certainly no evidence of a metabolic benefit.
The wider randomized record
- Across cancer types (treatment): A 2022 meta-analysis of 22 RCTs (5,943 participants) found metformin had no effect on progression-free survival (HR 0.97, 95% CI 0.82–1.15) or overall survival (HR 0.98, 95% CI 0.86–1.13). A marginal signal in reproductive-system cancers was undercut by later, larger trials, while digestive-system cancers actually trended worse (HR 1.45, 95% CI 1.03–2.04).
- Preventing new cancers: A separate meta-analysis of 27 RCTs (over 20,000 people, 378 new cancers) found no preventive effect on cancer incidence (relative risk [RR] 1.07, 95% CI 0.87–1.31) — enough statistical power to rule out a meaningful benefit.
- Advanced prostate cancer (STAMPEDE): In 1,874 men with metastatic hormone-sensitive prostate cancer starting androgen deprivation therapy (ADT), metformin did not improve overall survival overall, though it did ease ADT’s metabolic side effects. A subgroup hinted at a survival benefit only in men with more advanced (higher-volume) disease.
Where a signal still survives
Despite the string of null results, a few narrow, higher-risk settings still show promise — the kind of precise questions worth better trials:
- Colorectal adenoma prevention. In a Phase III RCT of 151 non-diabetic patients who had already had pre-cancerous polyps (adenomas) removed, a low 250 mg dose of metformin cut the risk of new adenomas by about 40% over one year (RR 0.60, 95% CI 0.39–0.92), with no serious adverse events. A 2025 Chinese RCT in an even higher-risk group (3+ prior adenomas) found similar reductions in recurrence. A small trial in familial adenomatous polyposis (FAP), an inherited high-polyp syndrome, showed no benefit — but it was tiny and involved lifelong genetic mutations. For context, see our guide to colorectal screening.
- Endometrial protection. Because obesity and insulin resistance drive endometrial cancer, metformin has been tested across the disease’s spectrum. Small studies suggest it may help reverse endometrial hyperplasia (EH) — especially when combined with progestins — and may blunt the endometrial thickening caused by tamoxifen in breast-cancer patients. The underlying trials are small and uncertain, so these remain hypotheses, not conclusions.
The exercise trade-off — still the biggest caveat
Even setting cancer aside, there is a well-documented reason for healthy people not to take metformin casually: it appears to blunt the adaptations to exercise, arguably the most powerful longevity intervention we have. If metformin dampens the gains from strength training and other exercise, that is a meaningful cost to weigh against speculative benefits.
The bottom line for 2026
Failed trials are most useful when they tell us which big hypotheses to drop. The randomized evidence now argues against “metformin in the water” for everyone chasing longevity or cancer prevention. What remains is a case for precision: a cheap, generic drug that may help specific, well-defined, higher-risk groups — and that should motivate better trials rather than broader use. For our fuller take on separating longevity hype from evidence, see Reversing Aging and our review of Peter Attia’s Outlive.
Leading Anti-Aging Scientists Who Have Taken Metformin
Note: these are historical statements of personal use and are not endorsements. As the evidence above shows, several prominent researchers have grown more skeptical of metformin as an anti-aging tool.
- Ray Kurzweil
- David Sinclair
- Nobel laureate James Watson
- Robert Hariri, co-founder and president of Human Longevity Cellular Therapeutics
Dosage
- Varies from 500 mg to 2500 mg by formulation. See Mayo Clinic recommendations.
- In the United States, metformin requires a doctor’s prescription.
- Metformin has an oral bioavailability of 50–60% under fasting conditions, and is absorbed slowly.
- Metformin is not metabolized. It is cleared from the body by tubular secretion and excreted unchanged in the urine; it is undetectable in blood plasma within 24 hours of a single oral dose. The average elimination half-life in plasma is 6.2 hours. Metformin distributes to (and appears to accumulate in) red blood cells, with a much longer elimination half-life of about 17.6 hours (reported as ranging from 18.5 to 31.5 hours in a single-dose study of non-diabetics).
Clinical Trials
- Cancer trials (2016–2025): The MAST trial and the meta-analyses discussed in the section above represent the current randomized evidence on metformin and cancer — largely negative, with narrow exceptions.
- Metformin in Longevity (MILES) concluded in 2018. It showed improved insulin sensitivity but, of concern, also found significantly reduced gene expression in muscle — an early hint of the exercise trade-off. MILES identified biomarkers intended for use in the TAME trial.
- TAME (Targeting Aging with Metformin): A long-proposed, roughly six-year, $77 million effort involving about 3,000 patients, championed by Dr. Nir Barzilai. Despite years of effort, funding has remained the central obstacle — a recurring theme for trials of cheap, generic drugs with no commercial sponsor.
- Berberine vs. metformin — see our companion article on this plant-derived alternative.
Side Effects and Adverse Events
- Metformin is generally well tolerated.
- Common side effects include diarrhea, nausea and abdominal pain.
- It carries a low risk of causing low blood sugar.
- High blood lactic acid (lactic acidosis) is a concern if the medication is prescribed inappropriately or in overly large doses.
- It should not be used in those with significant liver disease or kidney problems.
- Can significantly reduce gene expression in muscle, and may blunt the adaptations to exercise (see above).
- While no clear harm has been shown during pregnancy, insulin is generally preferred for gestational diabetes. (Wikipedia)
Data Sources
- Peter Attia MD — Metformin and cancer: active surveillance needed (July 2026)
- Fleshner NE, et al. Metformin Active Surveillance Trial in low-risk prostate cancer. J Clin Oncol. 2025;43(34):3662–3671. (Lay summary: The ASCO Post)
- Wen J, et al. Efficacy of metformin therapy in patients with cancer: a meta-analysis of 22 randomised controlled trials. BMC Med. 2022;20:402.
- Wikipedia — Metformin
- Healthspancampaign.org — Dr. Nir Barzilai on the TAME study
- Wired (a good, appropriately skeptical read on the trial statistics)
- NIH / PMC — metformin’s history and pharmacology
- Frontiers in Endocrinology
Related on Keep Health: Berberine · Nicotinamide Riboside (NR) · Reversing Aging · Dr. Raghav Sehgal’s Biomarker Research · Preventing Age-Related Diseases
