A new study suggests that type-2 diabetics who take metformin following a diagnosis of breast cancer lower their risk of dying of the disease by 50%. Here is a re-posting of my CTV.ca/health blog from 2009 reporting on the science behind the story.
Is the anti-diabetic pill metformin also effective against cancer?
June 17, 2009 07:49 by Dr. Lorne Brandes
In my June 9 blog, I explained why off-patent drugs usually are not developed for new uses, such as cancer treatment. It generally boils down to money: because of the ready availability of cheaper generic versions, major pharmaceutical companies are reluctant to invest tens, or hundreds, of millions of dollars in the clinical cancer trials required to gain regulatory approval of a new use for their old drug.
Well, I have just learned that one old drug could prove to be an exception to that rule (As we say in medicine, “Never say ‘never’ and never say ‘always’”).
Its name is metformin, an oral medication widely used to treat adult (type 2) diabetes mellitus (DM2). Although its composition patent lapsed in 2002, and despite the fact that cheaper, FDA-approved, versions are now made by at least fifteen generic drug companies, metformin is still marketed under the trade name Glucophage by its original developer, Bristol-Myers, Squibb.
Given the increasing epidemic of DM2 in affluent countries of the western world, it seems that everyone still manages to reap a profit from this effective old warhorse!
Now comes exciting new evidence that what works in diabetes may also work in cancer. Here’s the story.
For some years, DM2 has been recognized as a risk factor for developing cancer. The association may be largely indirect, through obesity, which is prevalent in type 2 diabetics.
Too much body fat often results in what is called “insulin resistance”: far from producing too little insulin, the pancreas in obese subjects with DM2 produces too much of the hormone in response to the increased blood sugar. High levels of insulin and insulin-like growth factors (IGFs) are strongly implicated in the causation of cancer in laboratory rodents and in humans.
Metformin is especially effective in obese diabetics who overproduce insulin. By activating an important enzyme, called adenosine monophosphate kinase (AMPK), metformin prevents the liver from breaking down starch into sugar and stimulates uptake of sugar by the body’s muscles. As a result of this one-two punch, blood sugar and insulin levels fall.
Now for the cancer connection.
By activating the same AMPK enzyme in cancer cells, metformin inhibits malignant growth in the test-tube and in mice. The AMPK enzyme also interacts with other genes and proteins involved in aggressive malignant behaviour. Indeed, metformin is highly active in the test-tube against cells derived from “triple negative” breast cancer, a form of the disease with an especially poor prognosis.
Based on the accumulating laboratory data, researchers at Scotland’s University of Dundee compared the risk of cancer in 983 patients with DM2 who took metformin and 1,846 diabetic controls who did not in a study published in the British Medical Journal. They found that diabetic patients who took metformin had a significantly lower cancer rate. Those taking the highest doses of metformin for the longest period of time, had the lowest cancer rate (a 44% decrease as compared to diabetic controls who did not take metformin).
Now, with a just-released study published in the Journal of Clinical Oncology (JCO), the metformin train appears to be leaving the station.
Doctors at Houston’s M.D. Anderson Cancer Center assessed the effects of chemotherapy, given before surgery, on locally advanced breast cancer among 88 patients with DM2 who took metformin, 87 patients with DM2 who did not take metformin, and 2,374 non-diabetic patients. After the chemotherapy, all patients underwent mastectomy or lumpectomy; lymph nodes draining the breast were sampled in all cases.
Pathologists closely examined each surgical specimen under the microscope to determine the presence or absence of residual cancer cells. Cases in which there was no residual cancer following the chemotherapy were called “pathological Complete Responses (pCR)”.
The study found a significantly higher rate of pCR (24%) in patients with DM2 who took metformin at the time of chemotherapy than in patients with DM2 who did not take metformin at the time of chemotherapy (8% pCR). Non-diabetic patients also had a lower pCR rate (16%) than patients with DM2 who took metformin, but the difference did not reach significance.
In an accompanying JCO editorial entitled, “Metformin in breast cancer: Time for action,” the University of Toronto’s Dr. Pamela Goodwin and her colleagues announced plans for a large international phase 3 study to be led by the Clinical Trials Group of the National Cancer Institute of Canada. It will compare the effect of adding metformin or a placebo to chemotherapy following surgery for early breast cancer. The study will include both patients with DM2 and high insulin levels, and non-diabetic women.
Will metformin, the old, wildly successful anti-diabetic drug, morph into metformin, the new, wildly successful anti-cancer drug? Although nobody yet knows, one thing is certain: a positive outcome should generate even more hefty profits for both Bristol-Myers and its generic competitors!