Scots unlock secrets of diabetes drug - and hopes for future

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SCOTTISH scientists have found new genetic links that explain how a common drug to treat diabetes works, giving hope for new treatments to be developed.

Metformin is taken by millions of people with diabetes around the world and has been used for more than 50 years. But until now, experts have not known exactly how the drug works.

A team of researchers at the University of Dundee have found how a gene known as ATM affects how well metformin works in different patients.

They now hope it will lead to new drugs being developed which are even more successful at tackling the increasingly common disease.

As well as treating diabetes, metformin has also been shown to protect against heart disease and eye and kidney disease in people with Type 2 diabetes. It can also have benefits against cancer.

Dr Ewan Pearson, Professor Colin Palmer and colleagues based in the Biomedical Research Institute at the University of Dundee used data from patients with diabetes and blood samples donated by 20,000 people in the Tayside area in the research.

They found that how well patients responded to metformin was affected by one particular chromosome and the gene ATM - ataxia telangiectasia mutated - which was found in this region of a person's genetic make-up.

This findign was backed up by researchers who carried out another study at Oxford University, using a large prospective clinical trial, the UK Prospective Diabetes Study, in more than 1,100 people taking metformin for the treatment of diabetes.

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," he said.

"We were expecting to find genes involved in blood sugar regulation so the finding that ATM is involved in metformin response was totally unexpected.Although ATM has been widely studied by cancer scientists, no-one previously thought it had a role in how this commonly used diabetes drug worked.

"Our finding therefore draws together mechanisms that protect against cancer and lower blood sugar, suggesting a new area for diabetes drug development."

Prof Palmer said: "This is an important development in defining how individuals may respond differently to diabetes drugs, but further work is required before we have enough information to be able to reliably use genetic testing in the clinic to guide treatment of common forms of Type 2 diabetes."

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

Charity Diabetes UK has Dr Pearson more funding to continue the work using genetic techniques in a group of 8,000 people with Type 2 diabetes.

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