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New drug candidate developed for the treatment of type 2 diabetes

Researchers from Helmholtz Munich, the German Center for Diabetes Research (DZD) and Novo Nordisk have developed a new hormonal combination for the future treatment of type 2 diabetes. #Scientists have combined the hypoglycemic effects of the drug Tesaglitazar and GLP 1 hormone in a new highly effective active ingredient. When combined with GLP 1, the new molecule only reaches tissues containing the GLP 1 receptor. This reduces the side effects of Tesaglitazar and increases the effects on sugar metabolism. The new active ingredient has already been successfully tested in animal models. The results have now been published in »Nature Metabolism«.

The active ingredient #Tesaglitazar improves glucose and lipid metabolism in patients with type 2 diabetes. It activates 2 receptors in the cell nucleus and thus improves insulin sensitivity. This has been shown in phase 3 clinical studies. However, Tesaglitazar also had some unwanted side effects, such as signs of kidney damage. In order to be able to use the active ingredient for therapeutic purposes, the researchers used a trick: they biochemically bound it to the gastrointestinal hormone GLP 1, which has been used successfully for the treatment of type 2 diabetes for several years. In this way, the combined drug can only be introduced into cells and tissues that possess the GLP 1 receptor. “With this trick, we have managed to combine the hypoglycemic effects of GLP 1 and tesaglitazar into a single, highly effective molecule. while keeping tesaglitazar away from the tissues in which it has harmful effects”, explains the author. study leader, PD Dr. Timo Müller, Director of the Diabetes and #Adiposity Institute and DZD scientist.

The new active ingredient improved glucose tolerance and therefore #sugar metabolism

The new #active has already been successfully tested in an animal model: “In obese and diabetic male mice, it improves sugar metabolism significantly more than treatment with the individual hormones GLP 1 or tesaglitazar alone – and that without side effects harmful to the liver or kidneys,” explains Professor Kerstin Stemmer, one of the first authors of the study. The active ingredient increased glucose tolerance particularly effectively. Minimal doses of the new active ingredient are sufficient to sustainably improve blood sugar metabolism. “The active ingredient could have great potential for the acute treatment of high blood sugar levels in type 2 diabetes,” says Aaron Novikoff, also the first author of the study.

Next, the researchers now want to investigate whether this active ingredient also has potential to treat type 2 diabetes in humans, and whether the effectiveness of this new combination therapy can be further optimized by additional biochemical modification.

context

A team led by Prof. Dr Matthias Tschöp (Scientific Director Helmholtz Munich) and Dr Timo Mueller as well as Richard DiMarchi, Ph.D. (Indiana University) and Dr Brian Finan (Novo Nordisk) have been working for years on new drug candidates for the treatment of type 2 diabetes and obesity. So-called polyagonists simultaneously mimic the effects of various hormones. In clinical studies, some of these polyagonists have shown great promise for improving the treatment of obesity and type 2 diabetes and are currently undergoing phase 2 and 3 clinical studies. dual agonists for the treatment of type 2 diabetes was approved in the United States this year. The drug combines GLP 1 and GIP (glucose-dependent peptide) receptor agonists that mimic the two gut hormones, GLP 1 and GIP.