Establishing the mechanism underlying the genetic association of a glucose transporter to metformin response to improve its use in the clinic
Metformin is one of the most commonly used drugs to treat Type 2 diabetes, but it’s only effective in two thirds of people and we don’t know why. Dr Sutherland wants to study the genetics of people with Type 2 diabetes, to see if it’s possible to predict whether treatment with metformin will be effective. This way, we could improve the strategies for personalising Type 2 diabetes therapies in the future.
Background to research
Metformin is used to control blood glucose levels in people with Type 2 diabetes around the world, but we know that it doesn’t work in everyone. Dr Sutherland has found that the effectiveness of metformin in people with Type 2 diabetes is influenced by a single gene, called GLUT2. This gene produces a GLUT2 protein that is responsible for moving glucose in and out of cells (an important process that ensures cells can use the glucose as fuel). Tiny differences in the GLUT2 gene may lead to a lower sensitivity to metformin. In order to understand how these genetic differences are related to the effectiveness of metformin, we need to see if metformin interacts with the GLUT2 protein in the cells. Once we have a picture of the relationship between metformin and the GLUT2 protein, it can be investigated further to develop potential drugs.
Dr Sutherland wants to figure out why tiny differences in the GLUT2 gene change the effectiveness of metformin, and whether higher doses of metformin could be used to overcome the gene’s influence. He’s planning to study how mice with high or low levels of the GLUT2 protein respond to metformin, and will investigate the molecular processes happening inside cells in response to metformin as well.
Potential benefit to people with diabetes
At Diabetes UK we are committed to finding better ways to treat Type 2 diabetes. We need to understand why metformin isn’t effective in everyone with Type 2 diabetes, and find ways to overcome this. This project will tell us whether higher doses of metformin might be more beneficial in people who are less responsive. It could also help to improve early diagnosis, aid prescribing decisions in the future, and potentially uncover new avenues for developing Type 2 diabetes drugs.