Summary: Studies show that the diabetes drug metformin reduces cancer rates by about a third. The drug is thought to ward off cancer by reducing blood sugar. Researchers are now conducting clinical trials on healthy senior adults. [Photo: Alexander Jenolyn F. Alexander, Veronika Kozlovskaya, Eugenia Kharlampieva and Biana Godin (NIH)]
Can a generic medicine costing 5 cents prevent cancer?
A growing body of evidence supports the idea that metformin prevents cancer. The theory goes like this. Sugar feeds cancer cells, and because the diabetes drug reduces blood sugar, then metformin reduces cancer.
Metformin was first approved for treating type 2 diabetes in France in 1957, the United Kingdom in 1958, and Canada in 1972, and by the FDA in 1994 Since then, metformin has become the drug of choice in treating type 2 diabetes.
Metformin is sold as a low-cost generic. The drug is widely expected to be used to fight the upcoming surge in type 2 diabetes. In some countries, metformin is fully approved as a prediabetes treatment, to prevent the onset of type 2 diabetes. In the United States, the FDA allows off label use for this purpose. Metformin is so important that it features a prominent place on the World Health Organization’s (WHO) List of Essential Medicines.
How Does Metformin Prevent Cancer?
In a nutshell, scientists believe that metformin starves cancer cells. High blood sugar increases cancer risk in healthy people. Cancer cells grow at an accelerated rate. They require vast quantities of sugar for fuel. Metformin prevents cancer by starving the cancer cell of sugar. Metformin decreases the growth of cancer cells both in the test tube and in the body.
Normal cells utilize oxygen for energy. However, cancer cells have a bizarre quirk which requires them to use glucose for energy. Metformin prevents cancer from growing by lowering blood sugar levels. Cancer cells need massive amounts of sugar, and metformin starves them and limits their rapid growth.
A cancerous tumor consists of 99% tumor cells and 1% cancer stem cells. Tumor cells are benign and cannot metastasize. Cancer stem cells are dangerous because they can metastasize, in other words, they can migrate and begin a new tumor growth in another location in the body. Metformin prevents cancer from growing by selectively targeting cancer stem cells.
Barzilai Says Metformin Prevents Cancer
Dr. Nir Barzilai is metformin expert and a celebrity in the anti-aging field. Dr. Barzilai came to fame when he spearheaded the Longevity Genes Project at Albert Einstein College of Medicine. The Longevity Genes Project is a study of more than 500 healthy centenarians to unlock their secrets to a long life.
In a recent essay in the journal Cell, Dr. Barzilai made a convincing case that metformin prevents cancer. Not only does the drug prevent cancer, Barzilai feels that metformin is an anti-aging drug in general. The boyish researcher cited evidence showing that metformin prevents cancer as well as heart disease, and Alzheimer’s disease.
Barzilai cited observational studies showing that metformin prevents cancer and cancer deaths. Dr. Barzilai cited individual observational studies by lead authors Libby (2009), Landman (2010), Lee (2011), and Tseng (2012), in which the authors showed that metformin prevents cancer and reduces cancer mortality. Barzilai states:
“Several epidemiologic studies have shown that metformin use is associated with reduced cancer incidence and mortality.” – Nir Barzilai, MD
Libby Study Shows Metformin Prevents Cancer
In an extensive research study, a team of British scientists showed that metformin prevents cancer, reducing the rate of the disease by more than fifty percent.
The team of researchers was led by Gillian Libby, MSC from the University of Dundee in the United Kingdom. They performed a massive data analysis, linking data from a population-based diabetes registry, a prescription drug use registry and a cancer registry. The team followed over 8,000 diabetics over a 10-year period during which they observed over 700 cancers. They compared diabetics taking metformin to those that did not. The researchers adjusted for age, sex, BMI, smoking status, and income.
At the end of the study, the researchers concluded that metformin prevents cancer and also reduced cancer deaths. Compared to the general population, the group taking metformin had a 54% lower incidence of all cancers.
The authors were also surprised to find that those who did get cancer exhibited a significantly higher survival rate, including those with malignant cancers of the colon, breast, and lung. The longer the people took metformin, the more cancers it prevented.
Bottom Line: An observational study of 8000 diabetics in the U.K. showed that metformin prevents cancer.
Metformin Prevents Cancer Says Bowker
A team of researchers led by Bowker from the Saskatchewan Provincial Health System (SPHS) also conducted a research study to see if metformin prevents cancer. The investigators in this observational study followed more than 10,000 patients for 5.4 years. The SPHS researchers found that metformin users died of cancer 30% less often than those taking another diabetes drug called sulfonylureas.
Bottom Line: Another observational study of 10,000 diabetics in Canada showed that metformin prevents cancer.
Metformin Prevents Cancer In Taiwanese Study
A team of researchers led by Lee examined the records of 800,000 Taiwanese individuals. The researchers found that metformin users had a much lower cancer rates. The authors were amazed by their findings and remarked:
“With diabetes but no anti-hyperglycemic medication, cancer incidence density increased at least 2-fold for total [total cancer], CRC [colorectal cancer], and HCC [hepatocellular (liver) cancer]. On metformin, total, CRC and HCC incidences decreased to near non-diabetic levels”
Bottom Line: An observational study of 800,000 Taiwanese diabetics showed that metformin prevented cancer, nearly reducing cancer rates to those of non-diabetics.
Gandini Shows That Metformin Prevents Cancer
The strongest evidence that metformin prevents cancer comes to us from a systematic review published in 2014 in the journal Cancer Prevention Research. Lead author Sara Gandini noticed that the evidence linking metformin to reduced cancer rates had been mounting over the years, with dozens of published studies on the subject. Some studies showed that metformin prevented cancer significantly, and others little to not at all. Does metformin prevent cancer or not? And if so, by how much? Sara Gandini and her colleagues decided to settle the question once and for all.
The Gandini team gathered all the observational studies that linked metformin to reduced cancer rates. After throwing out low-quality studies with skimpy data, the team wound up with 47 high-quality independent studies, each linking metformin use to reduced cancer rates. The team included the studies by Libby, Landman, Lee, and Tseng and many others. In total, the team documented over 65,000 cancer cases in diabetic patients. In a massive collation effort, the Gandini team pooled the results of the different studies. They also adjusted for variables that could sway the results, called confounders, such age, sex, BMI, smoking status, and time-lag bias.
After averaging the results of the different studies, the Gandini team showed that metformin prevents cancer. In fact, people taking metformin had 31% reduced cancer rates and 34% reduced cancer mortality.
Bottom Line: Because it includes the results of most of the metformin studies, the Gandini study is the strongest evidence that metformin prevents cancer in diabetics.
What Dose of Metformin Prevents Cancer?
Most clinical trials have given metformin in doses used to treat type 2 diabetes. The Diabetes Prevention Program (DPP), for example, gave patients 850mg of metformin twice daily.
To date, the human data on metformin’s cancer preventing abilities have come from only from epidemiologic studies. Observational studies are a weaker form of evidence than randomized controlled trials. However, don’t disregard the evidence. Remember the maxim “correlation does not imply causation – but it sure is a hint.”
Focus On Cancer Prevention
While researchers once exclusively focused on treating cancer, some research interest now focuses on preventing the disease with metformin. Numerous clinical trials are currently under way to investigate metformin’s potential to prevent many cancers, including endometrial, breast, colorectal, and prostate cancer. Several of these trials are funded by the National Cancer Institute (NCI) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
Diabetes Prevention Program (DPP)
Prediabetics are people with high blood sugar who are at increased risk of developing type 2 diabetes. The original DPP enrolled more than 3,000 prediabetics and randomly assigned them to one of three prediabetes treatment groups: one group received metformin, one took part in an intensive diet and physical activity program, and the control group was given a placebo.
The metformin group had a substantially lower risk of developing type 2 diabetes than the general population. Participants in the exercise and diet group had the best results. The researchers concluded that diet and exercise are the most effective prediabetes treatment.
The NCI and NIDDK have teamed up to study metformin’s ability to prevent cancer in a follow-up study called the DPP Outcomes Study (DPPOS). In this study, researchers are documenting cancer and death rates among study participants.
Metformin has yet to be tested in healthy adults. Most of the trials testing metformin’s cancer preventing powers have enrolled participants with special health conditions. These participants were either at an increased risk for cancer or diabetes, obese or had elevated glucose or insulin levels.
The NCI’s Brandy Heckman-Stoddard, Ph.D., MPH, is a key member of the DPPOS follow-up study and provides a rationale for the study:
“The randomized controlled trials that have been used to examine metformin’s potential as an anti-cancer agent in patients with diabetes have had an insufficient follow-up for cancer endpoints. “ She added: “These data also do not address the cancer risk in non-diabetic populations, in which the cancer preventive potential of metformin is unknown.”
Metformin’s Effects on Cancer Biomarkers
In addition to the DPPOS, the NCI and other organizations are conducting smaller trials to determine metformin’s effects on cancer biomarkers rather than on cancer itself.
Cancer takes a long time to develop, and a clinical trial that tests metformin’s cancer preventing abilities require a significant number of participants and many years. Researchers have discovered a more efficient way. Certain proteins or signaling pathways, called biomarkers, have been implicated in cancer development. Instead of large trials, smaller trials merely examine metformin’s effects on cancer biomarkers. NCI and other organizations are currently funding many 3 to 6-month trials to investigate whether metformin affects specific cancer biomarkers. The theory is that if metformin reduces cancer biomarkers, then it is likely that metformin prevents cancer. The studies below are ongoing and have not yet reported results.
Most of the trials are evaluating metformin’s effects on biomarkers in cancer survivors. For example, in the study “Exercise and Metformin in Colorectal Cancer Survivors,” researchers from Dana-Farber Cancer Institute are seeing if metformin prevents cancer in colorectal cancer survivors, by measuring changes in their insulin levels and other biomarkers.
In the study titled “An Endometrial Cancer Chemoprevention Study of Metformin [and Lifestyle Intervention]” researchers at the University of Texas MD Anderson Cancer Center are studying obese post-menopausal women who are at risk for endometrial cancer. The researchers are investigating whether metformin affects insulin levels and biomarkers in the endometrium.
Take Home Message
- Gandini’s systematic review of dozens of observational trials provides strong evidence that metformin prevents cancer. Those taking metformin had 31% reduced cancer rates and 34% reduced cancer mortality.
- So far, metformin prevents cancer only in people with special health conditions, such as those with increased risk for cancer or diabetes, obesity or with elevated glucose or insulin levels.
- Observational trials aren’t as reliable as clinical trials; researchers are conducting short-term clinical trials to see if metformin reduces cancer biomarkers. If it reduces cancer biomarkers, then it might prevent cancer.
Related Article: Besides preventing cancer, metformin has other anti-aging effects. Read about it in the linked article.
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1) Diagnosis, Advice, and Treatment: This article is intended for informational and educational purposes only and is not a substitute for professional medical advice. The information provided in this article should not be used during any medical emergency or for the diagnosis or treatment of any medical condition. A licensed physician should be consulted for the diagnosis and treatment of any and all medical conditions. Call 911, or the equivalent emergency hotline number, for all medical emergencies. As well, consult a licensed physician before changing your diet, supplement or exercise programs. 2) Photos, External Links & Endorsements: This article is not intended to endorse companies, organizations or products. Links to external websites, depiction/mention of company names or brands, are intended only for illustration and do not constitute endorsements.
- Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care. September 2009;32(9):1620-5.
- Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin. Diabetes Care. February 2006;29(2):254-8.
- Lee MS, Hsu CC, Wahlqvist ML, Tsai HN, Chang YH, Huang YC. 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. BMC Cancer. 2011;11:20. Available Online.
- Landman GW, Kleefstra N, van Hateren KJ, Groenier KH, Gans RO, Bilo HJ. Metformin associated with lower cancer mortality in type 2 diabetes: ZODIAC-16. Diabetes Care 2010;33:322–6. Available Online.
- Tseng CH. Diabetes and risk of bladder cancer: a study using the National Health Insurance database in Taiwan. Diabetologia. 2011;54:2009–15.
- Sara Gandini, Matteo Puntoni, Brandy M Heckman-Stoddard, Barbara K Dunn, Leslie Ford, Andrea DeCensi, and Eva Szabo. Metformin and Cancer Risk and Mortality: A Systematic Review and Meta-Analysis taking into account Biases and Confounders. Cancer Prevention Research (Phila). September 2014; 7(9): 867–885. doi: 10.1158/1940-6207.CAPR-13-0424