A breakthrough in diabetes research could fundamentally change the treatment of type 2 diabetes. Scientists at the Dr. Margarete Fischer-Bosch Institute for Clinical Pharmacology (IKP) in Stuttgart, in collaboration with international partners including the Karolinska Institute, Stockholm University and the company Atrogi, have developed a new type of active ingredient that effectively lowers blood sugar levels without putting a strain on the cardiovascular system. The results of the groundbreaking study were published in the renowned scientific journal Cell.

In type 2 diabetes, the body’s cells can no longer absorb enough sugar from the blood, which leads to increased blood sugar levels. Previous therapeutic approaches with beta-adrenergic agonists, which promote glucose uptake in the cells, have failed due to serious side effects such as increased blood pressure or cardiac arrhythmia. However, the newly identified active ingredient ATR-258 appears to overcome this hurdle. “Our aim was to decouple the undesirable side effects on the heart and circulation from the blood sugar-lowering signaling pathway of this receptor,” explains Prof. Dr. Volker M. Lauschke, Deputy Director of the IKP.

The road to success began with a virtual screening in which researchers at Stockholm University analyzed millions of molecules. They came across ATR-258, which was then tested for its effect in cell cultures. Promising results were followed by preclinical studies and a clinical phase I study with 48 healthy volunteers and 25 type 2 diabetics over six months. “The studies showed that ATR-258 significantly and long-lastingly reduces blood glucose levels, while we did not observe any negative effects on heart rate or arrhythmias,” emphasizes Lauschke.

Another advantage of the active ingredient is that it could improve the effect of so-called “weight loss injections”, which are based on incretin-based drugs. These promote insulin production and lead to weight loss, but have the disadvantage that patients lose not only fat but also muscle mass. ATR-258 prevents this muscle loss, making the therapy safer and more effective.

The findings form the basis for the development of a new drug that could be taken orally in the future – a step forward compared to previous injections. The next step is a Phase II study to further test its efficacy. The research community is optimistic about the future, as this approach could enable millions of people with type 2 diabetes to lead a better life.

Original Paper:

GRK-biased adrenergic agonists for the treatment of type 2 diabetes and obesity: Cell

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