The Dundee team, led by Dr Graham Rena of the Department of Cardiovascular and Diabetes Medicine, has furthered understanding of how the type 2 diabetes drug metformin actually works. They believe this may allow scientists to develop more effective ‘second-generation’ medicines in the future.
Even though the therapeutic action of metformin was first discovered in 1929, the target mediating these effects remained unclear until now. The Dundee group has discovered that important responses to metformin depend on the drug’s metal-binding properties. Drugs like metformin have been known to bind to copper since the 19th century, but the role of this in the anti-diabetic effects of the drug was unknown until now.
Dr Rena said, “We have demonstrated that cellular actions of metformin are disrupted by interference with its metal binding properties. This link will illuminate a better understanding of the molecular mechanisms enabling drug action. Further research is now needed to exploit the new tools that we have developed to establish how this unusual property of metformin enables it to be such an effective medicine.”
Metformin is widely used across the globe, and is prioritised over every other treatment option for type 2 diabetes sufferers. In addition, it is one of only two oral anti-diabetic agents in the World Health Organization’s Model List of Essential Medicines. Metformin is the best drug for prevention of the cardiovascular complications of diabetes, and has been shown to produce few adverse effects.
This latest study follows work by other investigators in Dundee who were the first to establish that metformin treatment affords type 2 diabetes patients protection against both cancer and cardiovascular disease.
In recent years, it has been shown that metformin displays promise as a treatment for many other conditions and Dr Rena believes this study will further the potential for its use in a number of other situations.
“Metformin is also being investigated for efficacy in a wider range of age-related diseases including cancer, cardiovascular and neurodegenerative disease,” he continued. “Identification of metformin’s target will stimulate the development of second-generation drugs based on metformin, which has been impossible up until now.”
The research, which was funded by Tenovus Scotland, appears in a paper in the current edition of the journal Diabetes.
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