New fat-burning diabetes pill protects muscle and appetite

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.

The work represents a collaboration involving Professor Volker M. Lauschke and teams from Karolinska Institutet, Stockholm University, Uppsala University, the University of Copenhagen, Monash University, and the University of Queensland. Funding came from the Swedish Research Council, the Swedish Society for Medical Research, the Novo Nordisk Foundation, and additional sources.

Several authors are employed by or hold shares in Atrogi AB, which financed the clinical trial. Tore Bengtsson is the founder and chief scientific officer of Atrogi AB, which is continuing to develop the drug candidate, and he and a co-author have applied for patents related to the substances examined in the study. Additional company affiliations are detailed in the full publication.