Old dog, new tricks: more than meets the eye to Metformin – Dr Eleanor Kennedy

Last year, metformin celebrated its 60th anniversary and is still the first-line treatment for Type 2 diabetes. And recent research suggests new applications of this traditional medication in cancer, cardiovascular risk, ageing and pregnancy. Dr Eleanor Kennedy, Research Manager at the Diabetes Research and Wellness Foundation, explains how metformin is enjoying a new lease of life.

As a society, we love new stuff tempted by the latest mobile phones, computers and wide-screen televisions. But rotary dial telephones, portable typewriters and old cathode ray tube televisions still work just as well as they ever did.

The same is true of the drug market. Over the last few years, the number of new tablets being added to the diabetes drugs cupboard has been impressive. Yet, quietly in the background, Metformin, the workhorse of the Type 2 field, plods on not bothered by the new kids on the block.

Thanks to its popularity as the front line drug of choice and despite its well-documented side effects like flatulence, vomiting and other gastrointestinal problems, Metformin is safe in the knowledge that it is Metformin and not any of the other oral drugs used to treat Type 2 diabetes that is recognised on the influential World Health Organisation’s List of Essential Medicines.

But, as both the time required and cost involved in bringing new drugs to market continue to grow out of control, researchers are now looking for cheaper alternatives. Making existing drugs work harder is one way to do this and new research is suggesting that Metformin could have some exciting new applications.

Metformin is found in the plant Galega officinalis, better known as French lilac or Goat’s Rue. In 1640 an English herbalist, recommended Goat’s Rue as the go-to plant for, among other things, bites and stings measles, smallpox and worms in children. It was not until the late 1950s that Metformin found its true calling as a drug to treat diabetes.

Over the past few years, Metformin is being used in exciting ways proving that you can teach an old dog new tricks.

Metformin and cancer in Type 2 diabetes

Some studies now suggest that Metformin could be used not just as a treatment for cancer, but as a way to prevent it in people with diabetes at increased risk. One of the very first studies to show this was a Diabetes UK-funded grant awarded to Professor Dario Alessi in 2005.

At the time, health informatics (the science of using technology and patient data) was a very young science but the group, looking at computer-based patient files in Scotland, showed that Metformin may be connected to about a 30% lower risk of cancer in patients with Type 2 diabetes. There is now evidence to suggest that Metformin can delay certain soft tissue tumours.
With more than 120 million prescriptions of Metformin written every year for the treatment of Type 2 diabetes, Professor Lewis Cantley, the Director of the Cancer Centre at Weill Cornell Medicine known for his important work on cancer research, once commented that “Metformin may have already saved more people from cancer deaths than any drug in history”.

Metformin and Type 1 diabetes

And it’s not just the cancer field where Metformin is causing excitement. It is well known that insulin treatment in people with Type 1 diabetes is not always perfect and, even with careful management, many patients struggle to achieve their blood sugar targets. Although it isn’t recognised as a drug to treat Type 1 diabetes, metformin is sometimes used in patients to help limit the amount of insulin they need. However, Metformin is not licensed for use in Type 1 diabetes in the UK and there have been only a handful of carefully monitored, randomised trials of metformin use in Type 1 diabetes. Further research must test any longer-term benefits.

Metformin and ageing

Research is also showing that certain drugs can extend the length of time that male mice live and humble Metformin could be one to watch. The drug can increase the lifetime of a type of earthworm regularly used by geneticists by about 26%. In humans, however, the jury is still out and more research is needed to see how Metformin could reverse the signs of premature aging in humans.

Other possibilities

Metformin is already widely used during pregnancy in women with polycystic ovary syndrome and, although its use is still a matter of debate, guidelines in some counties like South Africa recommend Metformin in cases of diabetes diagnosed during pregnancy as well.

So it would appear that, although no-one is really 100% certain about how Metformin works, this wonder drug has much still to give. New research, including perhaps some funded by Diabetes UK, may give us new insights into the future potential of Metformin.

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