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Novel Molecule May Rival GLP-1s for Diabetes and Obesity Treatment

Novel Molecule May Rival GLP-1s for Diabetes and Obesity Treatment

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The popularity of GLP-1-based drugs is testament to the importance of a drug that increases fat burning and lowers blood sugar. Now, a new drug—taken in the form of a tablet—offers the outcome of GLP-1-based drugs (which are administered via injection) but with a different mechanism of action.

GLP-1 drugs affect hunger via signals between the gut and the brain, but often have side effects such as loss of appetite, reduced muscle mass, and gastrointestinal problems.

The newly published substance activates metabolism in skeletal muscle. In animal studies, the treatment has shown good effects on both blood sugar control and body composition, but without the side effects associated with today’s GLP-1-based drugs.

This work is published in Cell in the paper, “GRK-biased adrenergic agonists for the treatment of type 2 diabetes and obesity.”

An initial Phase I clinical trial involving 48 healthy subjects and 25 people with type 2 diabetes shows that humans tolerate the treatment well.

“Our results point to a future where we can improve metabolic health without losing muscle mass. Muscles are important in both type 2 diabetes and obesity, and muscle mass is also directly correlated with life expectancy,” said Tore Bengtsson, PhD, professor at the Department of Molecular Bioscience, Wenner-Gren Institute, Stockholm University and founder and CSO at Atrogi AB.

The drug substance is a β2 agonist developed in a laboratory. The molecule can activate important signaling pathways in the body in a new way, which has a positive effect on the muscles without overstimulating the heart, which is a known problem with β2 agonists.

“This drug represents a completely new type of treatment and has the potential to be of great importance for patients with type 2 diabetes and obesity. Our substance appears to promote healthy weight loss and, in addition, patients do not have to take injections,” said Shane C. Wright, PhD, assistant professor at the Department of Physiology and Pharmacology at Karolinska Institutet.

This new type of drug not only works on its own but can also work in combination with GLP-1, thanks to their different mechanisms of action. “This makes them valuable both as a stand-alone treatment and in combination with GLP-1 drugs,” said Wright.

The next step is a larger, clinical Phase II study planned by Atrogi AB, the company developing the treatment. The aim of the study is to see whether the same positive effects seen in preclinical models also occur in people with type 2 diabetes or obesity.