• 10/31/2013

New approach to prevention and therapy

Multiple action intestinal hormone corrects diabetes

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.

Prof. Dr. Matthias Tschöp with members of his research group
Prof. Dr. Matthias Tschöp with members of his research group (Picture: A. Heddergott/TUM)

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.

Maximize metabolic effects

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.

Next generation of personalized therapies?
“Our results give us additional confidence that our combinatorial approach of modulating brain regulatory centers via natural gut hormone signals has superior potential for a transformative diabetes treatment”, explains Prof. Tschöp. He adds a note of caution however: “Still, this approach has to go through several more years of intense research, clinical testing, and safety evaluations, before these substances may become available for patients”. Dr. Finan, the first author of the study, points out that there may be unprecedented potential: “We are quite excited about this new multi-functional agent approach and believe it could become an integral part of a next generation of personalized therapies for type 2 diabetes, as the ratio of the GLP-1 and GIP signal strengths could be adjusted depending on the individual needs of patients.”

Further information
Original publication: Finan, B. et al. (2013). Novel Unimolecular Dual-Incretins Maximize Metabolic Benefits in Rodents, Monkeys, and Humans, Science Translational Medicine, doi: 10.1126/scitranslmed.3007218

Link to publication

Technical University of Munich

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