Scientists uncover gene variant that affects workings of diabetes drug
September 2016

Scientists have identified a genetic variant that affects how well diabetes patients respond to the drug metformin. As well as paving the way for a more personalised approach to diabetes treatment, the findings also reveal how metformin actually works. The study, funded in part by IMI’s diabetes projects DIRECT and SUMMIT, was published in the journal Nature Genetics. ###For 50 years, metformin has helped type 2 diabetes patients worldwide to control their blood sugar levels and avoid the heart, eye and kidney problems that often come with diabetes. However, over a third of patients do not respond to normal doses of the drug. Furthermore, despite its widespread use, little is known about how metformin works. In this study, researchers analysed the genomes of over 13 000 people in a hunt for genetic variants associated with different responses to metformin. They found that a variant of the gene SLC2A2 is associated with a stronger response to the drug. This gene is behind the creation of a protein called GLUT2 that is involved in transporting glucose around the body, and people with the gene variant were found to have lower levels of this protein in their liver and other tissues, impairing their bodies’ ability to handle glucose. Metformin reverses this deficiency, explaining why these people respond so well to the drug. What’s more, the genetic variant had a stronger effect in overweight people. In fact, overweight people with two copies of the variant had a response that was equivalent to taking an extra 500 mg dose of metformin. ‘This is an exciting discovery that demonstrates how a patient’s genetics can determine how well, or poorly, a drug works,’ said Ewan Pearson of the University of Dundee and the DIRECT project. ‘We need to undertake further clinical studies before we can change the way we use metformin, but this finding suggests that some patients should be treated with higher doses than others to achieve the same effect. This really does move us a step closer to truly targeted therapy in the treatment of diabetes.’

• Read the University of Dundee’s press release
• Read the University of California San Francisco news item

IMI diabetes projects deepen cooperation
October 2013

IMI’s three diabetes projects – IMIDIA,  SUMMIT and DIRECT  – are set to deepen their cooperation following the signature of a new Memorandum of Understanding (MoU) that formally creates the ‘IMI Diabetes Platform’.### ‘With a combined budget of €100 million and the involvement of over 300 leading experts in diabetes, this is one of the world’s leading initiatives in this area focusing on overcoming key bottlenecks for novel therapies and improved disease management,’ the projects write in a press release announcing the MoU. ‘The importance of the findings of the IMI diabetes projects will be strongly increased by the multiple opportunities for information exchange now enabled by the implementation of a formal collaboration framework for the IMI Diabetes Platform.’ The projects have already been collaborating informally for some time. For example, they jointly organised a symposium to present their results at the recent annual meeting of the European Association for the Study of Diabetes (EASD) in Barcelona.  

IMI diabetes projects sign Memorandum of Understanding
November 2012

IMI currently has three projects working on diabetes – DIRECT, SUMMIT, and IMIDIA – which have a combined budget of just over €100 million. The projects tackle diabetes in different ways.### For example, IMIDIA focuses on studying the pancreatic beta cells which are responsible for producing insulin; it aims to use this knowledge develop treatments that can slow down the progress of diabetes. Meanwhile, SUMMIT’s work addresses the urgent need for new treatments to tackle the complications associated with diabetes, such as eye, kidney, and blood vessel problems. Finally, DIRECT takes a personalised medicine approach to diabetes, as it works to identify different varieties of diabetes and effective treatments to tackle them. The projects already work together on an informal basis (as evidenced by their new joint leaflet produced with the support of the IMI Executive Office). However, IMIDIA and SUMMIT have now taken their collaboration to a new level with the signature of a Memorandum of Understanding (MoU). The MoU covers the handling of intellectual property, the transfer of knowledge and materials, and confidentiality. The projects believe that the MoU could serve as a template for collaboration between other IMI projects in the future.