By Morgan Nwanguma
Researchers have created a novel oral medication that enhances metabolic activity in skeletal muscle rather than suppressing appetite, as GLP-1 drugs do. Early studies show it improves blood sugar regulation and fat metabolism while preserving muscle mass and causing fewer side effects. Because it works through a distinct biological pathway, the drug could potentially be combined with GLP-1 therapies to deliver even greater benefits.
A new muscle-targeted treatment for diabetes and obesity may provide strong metabolic improvements without many of the limitations associated with current GLP-1 medications. According to findings published in Cell by scientists from Karolinska Institutet and Stockholm University, the approach points to a promising new direction in metabolic disease treatment.
The tablet-based therapy operates very differently from injectable GLP-1 drugs such as Ozempic, which act on gut-brain signaling to reduce hunger. While effective, GLP-1 medications are often linked to side effects including reduced appetite, loss of muscle mass and gastrointestinal discomfort.
Focusing on Muscle Metabolism, Not Appetite
Rather than targeting hunger, the new compound directly increases metabolic activity in skeletal muscle. In preclinical studies, it improved blood glucose control and body composition without the common drawbacks of existing GLP-1 treatments.
These findings are supported by a phase I clinical trial involving 48 healthy participants and 25 people with type II diabetes, which showed that the drug was 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 II 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 Generation of Safer β2 Agonists
The active compound is derived from a laboratory-engineered molecule belonging to the β2 agonist class. It engages critical signaling pathways in a unique way that enhances muscle metabolism and function, while minimizing the risk of cardiac over-stimulation commonly seen with conventional β2 agonists.
“This drug represents a completely new type of treatment and has the potential to be of great importance for patients with type II 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
By acting through a pathway different from that of GLP-1 medications, the drug shows promise both as an independent treatment and as a complementary therapy alongside 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 drug’s development will now progress to a larger phase II clinical trial, to be conducted by Atrogi AB, the company spearheading its advancement. This study will assess whether the encouraging outcomes seen in earlier studies can be replicated in people living with type II diabetes or obesity.
The research is the result of a broad international collaboration led by Professor Volker M. Lauschke, involving scientists from Karolinska Institutet, Stockholm University, Uppsala University, the University of Copenhagen, Monash University, and the University of Queensland. Financial support was provided by the Swedish Research Council, the Swedish Society for Medical Research, the Novo Nordisk Foundation, and other funding bodies.
Several of the study’s authors are employees or shareholders of Atrogi AB, which funded the clinical trial. Tore Bengtsson, the company’s founder and chief scientific officer, continues to oversee development of the drug candidate, and he and a co-author have filed patent applications covering the compounds studied. Further details on corporate affiliations are available in the full publication.
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