Scientists from the Helmholtz Zentrum München (HMGU) and the Technische Universität München (TUM), together with scientists in the USA, have developed a new therapeutic approach for treatment of type 2 diabetes. A novel single molecule hormone, which acts equally on the receptors of the insulin-stimulating hormones GLP-1 and GIP, was observed to reduce weight and improve blood sugar. The results have now been published in the medical journal 'Science Translational Medicine', and include data from successful clinical studies in partnership with the pharmaceutical company Roche.
GLP-1 (glucagon-like peptide 1) and GIP (gastric inhibitory peptide) are hormones that are formed by the digestive tract and that control food intake and numerous metabolic processes. When glucose (sugar) is ingested, these hormones primarily lead to increased insulin release and subsequent reduction in blood sugar, but they also affect appetite regulation and fat burning.
Some of the actions, which are combined in one molecule for the first time, are already in use for the treatment of type 2 diabetes. GLP-1 analogues, as well as DPP4 (dipeptidyl peptidase 4) inhibitors, which are thought to enhance GLP-1 action, are used to reduce blood sugar. A HMGU and TUM team led by Dr. Brian Finan and Prof. Dr. Matthias Tschöp at the Helmholtz Diabetes Center, working with Richard DiMarchi from Indiana University and colleagues from the University of Cincinnati, have now succeeded in developing a molecular structure that combines the effects of the two hormones. These novel molecules simultaneously stimulate two receptors (GLP-1 and GIP) and consequently maximize metabolic effects compared to each of the individual molecules, or currently available medicines that are based on individual intestinal hormones.
The newly discovered GLP-1/GIP co-agonists lead to improved blood sugar levels and to a significant weight loss and lower blood fat. Importantly, the researchers observed that the new substance also improved metabolism in humans, in addition to beneficial effects they discovered in several animal models. At the same time, there are indications that possible adverse effects, the most frequent of which are gastrointestinal complaints, are less common and less pronounced with this approach than with the individual hormones.