Why a diabetes drug fell short of anticancer hopes

But the latest research has convinced Pollak and some others that treatment of cancers should be taken off the list.

More studies, but no proof

One of the first hints linking metformin to anticancer effects came in a short note in the British Medical Journal in 2005. Researchers analyzed medical records of almost 12,000 people from the Tayside region of Scotland who were newly diagnosed with diabetes between 1993 and 2001. Of those, more than 900 went on to develop cancer. Interestingly, those who’d taken metformin at some point during the study period were 23 percent less likely to have received a later cancer diagnosis.

This finding fueled further research on people with diabetes taking metformin and the risk for breast cancer, liver cancer, ovarian and endometrial cancer, and other types. The authors of a 2013 analysis, covering more than 1 million patients in 41 observational studies like the original one, concluded that metformin “might be associated with a significant reduction in the risk of cancer.” But such associations are not proof.

Researchers went on to explore the link in studies with cells in dishes and in lab animals, finding that metformin slowed growth of blood, breast, endometrial, lung, liver, stomach, and thyroid cancer cells. It also seemed to make cancer cells extra sensitive to chemotherapy drugs. In one mouse study, scientists grafted human breast, prostate, or lung cancer cells into the animals and treated them with either standard chemotherapy drugs, metformin, or a combination of both. The combination worked best, preventing tumor growth and prolonging relapse.

These findings made sense to researchers. Metformin treats metabolic problems in diabetes, and cancer has also been linked to metabolic issues such as obesity. Even before the 2005 British Medical Journal study, Goodwin had noticed that breast cancer patients with high insulin did worse than those with normal insulin levels.

That logic, plus the promising data, led scientists to conduct a number of randomized controlled trials—the gold-standard experiment in medicine. Researchers would enroll people with cancer and split them into two groups. One group would get standard cancer therapy plus metformin; the other group would get standard therapy plus a placebo, a pill containing no medication.