The treatment, which is taken as a tablet, works in a completely different way from well-known GLP-1-based medications such as Ozempic that are given through injections. GLP-1 drugs influence hunger by altering communication between the gut and the brain, and they can cause side effects that include appetite loss, decreased muscle mass, and gastrointestinal discomfort.
Targeting Muscle Metabolism Rather Than Appetite
Instead of acting on hunger pathways, the new compound boosts metabolic activity directly within skeletal muscle. In animal studies, it improved blood sugar levels and body composition while avoiding the drawbacks commonly linked to today's GLP-1-based treatments.
A phase I clinical trial involving 48 healthy volunteers and 25 individuals with type 2 diabetes indicates that the treatment is also well tolerated in humans.
"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 Tore Bengtsson, professor at the Department of Molecular Bioscience, Wenner-Gren Institute, Stockholm University.
A New Type of β2 Agonist Designed for Safety
The active substance is based on a laboratory-developed molecule, a form of β2 agonist. This molecule activates key signaling pathways in a novel manner that benefits muscle function while avoiding the heart overstimulation typically associated 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.
Potential as a Stand-Alone or Combination Therapy
Because this drug operates through a mechanism distinct from GLP-1 medications, it may be effective on its own or when paired with GLP-1 drugs.
"This makes them valuable both as a stand-alone treatment and in combination with GLP-1 drugs," says Shane C. Wright.
Next Steps and Research Collaboration
The next stage in development is a larger phase II clinical trial planned by Atrogi AB, the company leading the drug's advancement. This study will examine whether the positive effects observed in earlier research also appear in people living with type 2 diabetes or obesity.
Reference:
Aikaterini Motso, Benjamin Pelcman, Anastasia Kalinovich, 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. GRK-biased adrenergic agonists for the treatment of type 2 diabetes and obesity. Cell, 2025; 188 (19): 5142 DOI: 10.1016/j.cell.2025.05.042
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