Diabetes drug may cut cancer risk

LOS ANGELES — 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, published Wednesday, shows that the drug can reduce the development of lung tumors by as much as 70 percent, 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 the United Kingdom that found that diabetics taking metformin had a 40 percent 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 percent to 70 percent," depending on the type of cancer.

To learn more about it, Dennis and his colleagues used a well-known model of lung cancer, exposing mice to a carcinogen known as NKK, the most important carcinogen in tobacco smoke. All the mice given only NKK developed lung cancer, the researchers reported in Cancer Prevention Research.

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

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