NEW YORK (Reuters Health) - The suspected cancer-fighting effects of the cheap diabetes drug metformin just got more backing from two new studies in the journal Diabetes Care.
Metformin is taken by tens of millions of type 2 diabetics every day to help them control their blood sugar, but in recent years scientists have found it might have some unexpected effects on cancer, too.
For instance, the drug appears to shrink lung and breast tumors in mice, and people taking it have fewer cancers.
Such findings have stoked hopes that metformin might someday be used to prevent cancer in smokers and others at high risk of the disease.
"I think it is a scientific emergency to understand the basis of these kinds of observations," said Dr. Michael Pollak, a cancer researcher at McGill University in Montreal, Canada.
"If it's a false lead, we need to understand why," said Pollak, who was not involved in the new studies. "But if it's a true lead, it is one of the most important observations in a long time in the field of cancer prevention."
Metformin (also sold under the brand name Glucophage) has been on the market for many years and is generally considered safe, although it's not without side effects. Because its original patent has expired, a month's worth of pills can be bought for less than $10.
The new reports, one from China and one from Italy, still don't offer proof that metformin cuts people's cancer risks. But they bolster the case that it might.
In the Chinese study, researchers from Hong Kong followed more than 2,600 cancer-free diabetics over five years on average. Nearly five percent developed cancer, with older age and alcohol and tobacco use being risk factors.
After accounting for such factors, those who didn't take metformin were two to three times as likely to develop tumors as were those on the drug.
And the higher the dose of metformin, the lower the cancer risk, said Dr. Xilin Yang of the Chinese University of Hong Kong, who worked on the study.
In an e-mail to Reuters Health, Yang added that people with low levels of HDL cholesterol -- "good" cholesterol -- seemed to benefit the most from taking metformin.
Although only randomized studies can show cause and effect, Yang said the research team felt pretty confident that metformin did have anti-cancer effects. The study was funded by local research foundations, and one of Yang's co-authors has received payments from companies that make diabetes drugs.
"This study and similar preceding studies really support the idea that metformin might be useful for cancer, but they do not prove it," cautioned Pollak.
Earlier this year, a joint report from the American Cancer Society and the American Diabetes Association said patients with diabetes -- mainly those with type 2 diabetes -- have a higher risk of some cancers.
One theoretical possibility is that other diabetes drugs up cancer risk, so that metformin users might really be experiencing the lack of an increase instead of a decrease.
Diabetics often take insulin, for example, and many tumors have insulin receptors. These receptors are areas on the surface of the cancer cells that can take insulin from the blood and use it to help the tumor grow.
Because metformin reduces the need for insulin, the tumor cells would have less of it to use, and in principle that might explain the anti-cancer effects.
But that doesn't appear to be the full explanation, according to an Italian study led by Dr. Edoardo Mannucci of Careggi Teaching Hospital in Florence. Mannucci also has received payments from manufacturers of diabetes drugs, including insulin.
In that study, patients who took metformin had half the chance of getting cancer, even after factoring out insulin's influence.
"If you have a kind of diabetes where metformin will control your blood sugar, metformin should be the drug of choice," said Pollak, noting that guidelines also recommend the drug. "But not all diabetes can be successfully controlled with metformin."
Newer drugs such as thiazolidinediones -- a group of medications that includes GlaxoSmithKline's controversial Avandia -- may help some patients, but are far more expensive and can have serious side effects.
If metformin does turn out to protect diabetics against cancer, it doesn't mean the same would necessarily be true for non-diabetics.
Even if it is, there is no certainty that the benefits would outweigh the harms if millions of healthy people were to start gulping down the pills. Metformin lowers blood sugar, which helps people with diabetes, but is probably bad for those without it. And it has side effects, too.
The most common -- diarrhea, gas, nausea -- are considered minor, but in very rare cases, the drug can cause death. According to the U.S. Food and Drug Administration, 15 out of a million people taking metformin for a year will experience a fatal surge of lactic acid in their blood, earning the drug a "black box warning."
"The job now is to obtain the information to determine if a big prevention trial is justified and to narrow the definition of the people who might benefit," said Pollak. "We don't get clues like this every day."
SOURCE: http://link.reuters.com/zan94q and http://link.reuters.com/ben94q Diabetes Care, online October 27, 2010.
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