Repurposing the Diabetes Drug Metformin for Cancer Treatment

Type 2 diabetes is a disease that leaves a person unable to regulate their blood sugar levels, which can lead to too much sugar accumulating in the blood. Metformin, the 10p per pill treatment for diabetes, can correct this error to some degree by helping cells in the body to mop up the excess glucose and restoring normal blood sugar levels.

One way that metformin works is by getting inside cells and hitting a molecular switch that turns the cells into little sugar sponges, soaking up molecules of the sugar glucose floating in the blood. This molecular switch is an enzyme called AMPK, a master controller of shuttling glucose molecules from the blood, into cells. When you exercise, AMPK in your muscle cells switches on and glucose is pulled into the cells where it is used as fuel that helps you get your ‘personal best’ or do that extra rep.

Thanks to work by researchers like Dario, we now know that AMPK also plays an important role in cancer. In many cancers, the cells have lost their ability to use AMPK as a master switch. This disruption to how the cells utilise energy contributes to their uncontrolled growth and proliferation – the underlying feature of all cancers.

A big step forward

This was a big step forward for cancer research but it took an even bigger leap in thinking to realise the potential for how this finding could positively affect the lives of people with cancer.

“It was definitely a Eureka moment. And then you start to realise the implications of the results. It didn’t take long, weeks maybe, to make the connection.”

“You start thinking, how is this all linked? You have an enzyme that’s involved with exercise and diabetes, and a gene that when mutated causes malignant tumours potentially by stopping the enzyme from working. And then you remember that the drug metformin can switch on this enzyme, so maybe metformin could also be a way to counteract the development of tumours.”

Asking questions about cancer

Dario knew that metformin was able to switch on AMPK to help people with diabetes so he reasoned that maybe the drug could also provide protection against cancer. To test this, Dario and others based in Dundee dove into the clinical records of nearly 12,000 people diagnosed and treated for type 2 diabetes between 1993 and 2001, and looked at how many of them went on to develop cancer during their lifetime. Their analysis of the data revealed that the people with type 2 diabetes who were treated with metformin were at a lower risk of developing cancer.

“Around 2 per cent of the world’s population take metformin for diabetes,” said Dario. “And there’s a great quote from Professor Lewis Cantley at Cornell University, who said: ‘Metformin may have already saved more people from cancer deaths than any other drug in history’. But we just won’t know it yet.”