Diabetes drug can reduce risk of cancer, researchers find

A growing body of evidence suggests that the widely used diabetes drug metformin can reduce the risk of cancer, researchers said Wednesday.

A study in mice exposed to tobacco carcinogens shows that the drug can reduce the development of lung tumors by more than 70%, and results from a small clinical trial in Japan suggest it can reduce rates of colorectal tumors in humans. The National Cancer Institute is now organizing a clinical trial to test the drug in people who smoke, and other trials are testing it against breast and prostate cancer.

There is not yet enough evidence to recommend using the drug routinely for cancer prevention, but the evidence is strong enough that physicians and patients considering drug therapy for type 2 diabetes might want to lean toward metformin because of its ancillary effects, researchers said in a news conference.

“Among the various treatment options for type 2 diabetes, if all other things are equal, early evidence that metformin might have benefit on the oncology side may play a role in decision-making,” said Dr. Michael Pollak, a medical oncologist at McGill University in Montreal who surveyed recent metformin research in an article in the journal Cancer Prevention Research.

The drug is particularly promising, he added, because unlike use of finasteride for preventing prostate cancer or tamoxifen for breast cancer, metformin appears to act across a broad spectrum of cancers.

Metformin increases the sensitivity of cells to insulin. It is one of the most widely used diabetes drugs, with 40 million prescriptions written in the United States in 2008.

It also has a number of other biological effects, including inhibiting a key signaling process between receptors in cells (called mammalian target of rapamycin, or mTOR) and reducing circulating levels of insulin and insulin-like growth factor. All those actions may inhibit or prevent the growth of cancer cells.

Interest in metformin was stimulated by a 2005 observational study in Britain that found that diabetics taking metformin had a 40% lower risk of cancer than those taking other diabetes drugs. Several subsequent studies have found the same thing.

“The epidemiologic evidence in diabetic humans is convincing and strong,” said Dr. Phillip A. Dennis, a medical oncologist at the National Cancer Institute. “It is real, and the reduction in risk ranges from 30% to 70%,” depending on the type of cancer, he said.

To learn more about it, Dennis and his colleagues used a well-known model of lung cancer, exposing mice to a carcinogen known as NNK, the most prominent carcinogen in tobacco smoke. All the mice given only NNK, and no metformin, developed lung cancer, the researchers reported Wednesday in Cancer Prevention Research.

But mice given metformin orally had a 33% reduction in numbers of tumors and a 34% reduction in tumor size. Those given it by injection had a 73% reduction in tumor number. The National Cancer Institute is now planning and seeking approval for a clinical trial in human smokers.

In another report in the Cancer Prevention Research journal, researchers from the Yokohama City University School of Medicine and the National Cancer Center Research Institute in Tokyo gave metformin to 12 nondiabetic patients with what are known as aberrant crypt foci, precursors of colorectal cancer.

After a month of low doses of the drug, the scientists found a significantly lower number of foci in the treated patients compared with 14 patients who did not receive the drug.

“These are very promising and exciting results,” said Dr. Scott Lippman, a medical oncologist at the University of Texas MD Anderson Cancer Center and editor of the journal.

In an editorial accompanying the reports, Dr. Jeffrey A. Engelman of Massachusetts General Hospital and Dr. Lewis C. Cantley of the Beth Israel Deaconess Medical Center in Boston also praised the findings. They noted that “primary care physicians and endocrinologists may consider this information when choosing an antidiabetes regimen for patients, especially those at a higher risk for developing cancer.”

In a news conference, Cantley noted that clinicians would have to rely for now on epidemiological studies because “prevention trials take forever to get done, and metformin is off patent, so no drug company will pay for them.”

Added Pollak of McGill University, “We don’t want to ignore the evidence we have now.”