Diabetes drug might fight cancer

An ancient herbal remedy that constitutes the active ingredient in a modern diabetes drug may soon play a new role in combating cancer, two studies show. The findings, published in the September Cancer Prevention Research, support earlier population studies suggesting that diabetes patients receiving the drug, called metformin, are less prone to develop cancer.

Metformin helps to stabilize blood sugar by decreasing the liver’s glucose output and increasing the sugar’s use by muscle tissue. Scott Lippman, an oncologist at the University of Texas M.D. Anderson Cancer Center in Houston, estimates that more than 40 million metformin prescriptions have been filled in the United States. “It’s been around for a while,” he says.

In one of the new studies, Atsushi Nakajima of Yokohama City University School of Medicine in Japan and colleagues measured how metformin affected the development of tiny lesions in the colon. These lesions, called aberrant crypt foci, are precursors of polyps, which themselves can be the forerunners of colon cancer. Using colonoscopy data, the scientists identified 26 patients who had had polyps removed during a colonoscopy. The scientists randomly assigned some to get metformin and others to get a placebo.

After a month, the nine patients getting metformin who returned for a follow-up colonoscopy had substantially fewer lesions in the bowel than they had when they started on the drug, whereas 14 patients receiving a placebo had no change.

In the other study, a U.S. team induced lung cancer in mice with injections of a tobacco-based carcinogen. One week after the last shot, some mice were given either a low or a medium dose of metformin in their drinking water for 13 weeks. The tumor burden in these mice declined by 39 percent and 53 percent over that time, depending on the dose they received.

When the researchers delivered an even higher dose of metformin, this time by injection, the tumor burden shrank by 72 percent, says study coauthor Phillip Dennis of the National Cancer Institute in Bethesda, Md.

Metformin is a drug in the biguanide class. The drug is derived from the French lilac plant (Galega officinalis), also known as goat’s rue or Italian fitch. In medieval Europe the plant was used to treat frequent urination, says Michael Pollak, an oncologist at McGill University in Montreal. Modern-era scientists took an interest in the biguanides in the 1920s, and found they could use the compounds to lower blood sugar in rabbits.

Metformin was derived from the plant in the 1950s in France and was approved by the U.S. Food and Drug Administration  in 1994 as Glucophage (literally “glucose eater”). The drug has since become generically available under the name metformin.  

A history of use with few side effects may help metformin as it faces regulatory hurdles to become a cancer fighter, Lippman says. “A lot is known about the safety of this,” he says. “From a research perspective, this is extremely exciting. The next step will be to take it to a clinical trial.”

Less clear is the mechanism by which metformin seems to inhibit cancer, and which cancers would be most susceptible if it succeeds. Earlier, Pollak’s team had shown that metformin could inhibit growth of breast cancer cells in a lab dish by awakening an enzyme called AMPK. The group further found that revved-up AMPK inhibits the activity of mTOR — a protein involved in cell growth and proliferation. That could explain part of metformin’s apparent anticancer effect, Pollak says. But, he adds, “We are not yet in a position where we understand perfectly how it works.”

The cancer connection didn’t come out of the blue. In recent years, several population studies have noted that type 2 diabetes patients on metformin seem less likely than others to develop cancer.