Metformin Code Cracked

Scientists in Scotland have used samples taken from 20,000 patients in Tayside to help make a breakthrough in the treatment of diabetes.

Academics from the Biomedical Research Institute at Dundee University played a key role in establishing how the drug metformin actually works.

Metformin has been used worldwide for more than 50 years by people with Type 2 diabetes but scientists have never known exactly how it helped sufferers.

The development means the scientists may now be able to develop the drug to help extend its use.

The team at Dundee used the clinical data of patients with diabetes, linked to donated blood samples from the Tayside area.

They identified a gene that helps to show how the body works with and makes use of metformin, which has been shown to protect against heart, eye and kidney disease in those with the metabolic disorder. It is also recognised as holding benefits against cancer, but scientists have never been able to explain why.

The condition usually affects overweight people and is caused by too much glucose, a type of sugar in the blood. It differs to Type 1 diabetes, which is an insulin-dependent condition usually diagnosed in childhood.

Around 228,000 people are thought to suffer from both types of the disorder in Scotland.

Dr Ewan Pearson and Professor Colin Palmer were among the researchers at the university who were able to determine how well metformin worked.

They identified an area of chromosome 11, which includes a gene called ATM (Ataxia Telangiectasia Mutated), that altered how people responded to metformin. This was also found by researchers in Oxford.

“ATM is a gene that is known to be involved in the DNA damage response system of cells, a mechanism that if faulty can lead to the development of cancer,” Dr Pearson said.

“In one of the largest studies of its kind, we have used the genetics of drug response, otherwise known as pharmacogenetics, to investigate how metformin works.

“We were expecting to find genes involved in blood-sugar regulation so the finding that ATM is involved in metformin response was unexpected.”

Although the ATM gene has been widely studied by cancer scientists, no-one has previously thought it had a role in how this commonly used diabetes drug worked.

Dr Pearson added: “Our finding therefore draws together mechanisms that protect against cancer and lower blood sugar, suggesting a new area for diabetes drug development.”

The research was funded by the Wellcome Trust and Diabetes UK and is published in the journal Nature Genetics.

Professor Peter Donnelly, who leads the Wellcome Trust Consortium at Oxford University and was a lead investigator in the study, said: “We have shown how useful genetics can be in shedding light on how drugs work.

“In addition, this study is the first to robustly identify a gene to be involved in how metformin works, and is there- fore an important first step towards understanding how an individual’s genes can affect the way they respond to treatment.”

Diabetes UK has awarded Dr Pearson further funding to continue the research using new genetic techniques on 8000 people with Type 2 diabetes.

Dr Iain Frame, director of research at leading health charity Diabetes UK, said: “This study is a great example of how research can produce unexpectedly exciting results.

“The benefits for people with Type 2 diabetes may not be immediate but any research that increases our knowledge of how effectively drugs work in different individuals is hugely important.

“This is why Diabetes UK is funding Dr Pearson to continue this important line of research and this is likely to have significant impact in the future for people with Type 2 diabetes and the costs involved to the NHS in treating Type 2 diabetes.

“An added bonus of this work is that the researchers have also discovered that this gene is involved in protecting the body against cancer.”