Researchers in an international study have uncovered new genetic evidence of how the benefits of the world’s most commonly used Type 2 diabetes drug may vary between individuals. Metformin, the drug used by hundreds of millions of people with Type 2 diabetes worldwide, has been in use for more than 50 years. It has been shown to protect against heart disease, eye and kidney disease in people with Type 2 diabetes, and has also been shown to have benefits against cancer. Metformin is also undergoing new clinical trials to determine if it can promote health aging.
It has been known for some time that metformin works better in some people than others but the reasons for this have not been understood. Now research led by the University of Dundee and University of California, San Francisco has identified a genetic variant (a change in the DNA code for a particular gene) that alters how well metformin works. Researchers found that overweight people carrying two copies of a genetic variant responded so much better to metformin that it was equivalent to receiving an extra 550mg of the drug. They say their findings represent a significant step towards personalised, targeted therapy in the treatment of Type 2 diabetes. The research has been funded by Wellcome, Diabetes UK and the National Institutes of Health in the US and is published in the journal Nature Genetics.
The Metformin Genetics Consortium identified a genetic variant in the gene encoding the glucose transporter GLUT2, a protein that plays an important role in transporting glucose inside the body. They showed that those people who carried this variant had reduced levels of GLUT2 in the liver and other tissues resulting in a defect in how the body handles glucose. Metformin acted to specifically reverse this deficiency resulting in a better response to metformin in people carrying this gene variant.
Dr Elizabeth Robertson, Director of Research at Diabetes UK, said, “This study sheds important light on why people with Type 2 diabetes respond differently to metformin, and could be used to identify distinct groups of patients or develop new therapies in the future. Altogether, this research represents an exciting step towards personalised therapy for Type 2 diabetes, moving away from a ‘one size fits all’ approach to ensure people receive the best treatment possible. Further work is now needed to understand how GLUT2 influences the way that metformin works inside the body, and we’re very pleased to see research funded by Diabetes UK moving the field of Type 2 diabetes treatment forwards.”
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