Lower blood sugar and increased fat burning - without negatively affecting appetite or muscle mass. These are some of the most promising effects of a new potential drug treatment for people with type 2 diabetes and obesity, according to a new study published in the journal Cell by researchers from Karolinska Institutet and Stockholm University.
The new drug, which is taken in tablet form, has a completely different mechanism of action than the well-known GLP-1-based drugs, such as Ozempic, which is administered via injections. 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 new substance instead 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.
An initial phase I clinical trial involving 48 healthy subjects and 25 people with type 2 diabetes shows that humans also 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," says one of the researchers behind the study, Tore Bengtsson, professor at the Department of Molecular Bioscience, Wenner-Gren Institute, Stockholm University.
The drug substance is based on a molecule-a type of β2 agonist that the researchers have 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," says Shane C. Wright , assistant professor at the Department of Physiology and Pharmacology at Karolinska Institutet, who is one of the researchers behind the study.
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," says Shane C. 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.
The study is the result of close collaboration with Professor Volker M. Lauschke and other researchers at Karolinska Institutet, Stockholm University, and Uppsala University in Sweden, the University of Copenhagen in Denmark, and Monash University and the University of Queensland in Australia. The research was funded by the Swedish Research Council, the Swedish Society for Medical Research, and the Novo Nordisk Foundation, among others.
Several of the article's authors are employed by and/or own shares in Atrogi AB, which funded the clinical trial. Tore Bengtsson is the founder and chief scientific officer at Atrogi AB, which is further developing the drug candidate, and has, together with a co-author, applied for patents for the substances investigated in the study. Several other company connections are reported; see the study for more detailed information.
Publication
"GRK-biased adrenergic agonists for the treatment of type 2 diabetes and obesity", Aikaterini Motso, Benjamin Pelcman, Anastasia Kalinovich, Nour Aldin Kahlous, Muhammad Hamza Bokhari, Nodi Dehvari, Carina Halleskog, Erik Waara, Jasper de Jong, Elizabeth Cheesman, Christine Kallenberg, Gopala Krishna Yakala, Praerona Murad, Erika Wetterdal, Pia Andersson, Sten van Beek, Anna Sandström, Diane Natacha Alleluia, Emanuela Talamonti, Sonia Youhanna, Pierre Sabatier, Claire Koenig, Sabine Willems, Aurino M. Kemas, Dana S. Hutchinson, Seungmin Ham, Lukas Grätz, Jan Voss, Jose G. Marchan-Alvarez, Martins Priede, Krista Jaunsleine, Jana Spura, Vadims Kovada, Linda Supe, Leigh A. Stoddart, Nicholas D. Holliday, Phillip T. Newton, Nicolas J. Pillon, Gunnar Schulte, Roger J. Summers, Ilga Mutule, Edgars Suna, Jesper V. Olsen, Peter Molenaar, Jens Carlsson, Volker M. Lauschke, Shane C. Wright & Tore Bengtsson, Cell, online June 23, 2025, doi: 10.1016/j.cell.2025.05.042
