Experimental Pill Shows Promise for Type 2 Diabetes and Obesity: Study

Researchers have found in a new study that a new experimental oral medication for type 2 diabetes and obesity may offer a novel treatment approach by activating skeletal muscle metabolism, rather than mimicking gut hormones like current GLP-1 receptor agonists.

Key findings:

• The drug works by enhancing the body's ability to use energy within skeletal muscles.

• This mechanism differs from GLP-1–based therapies, which primarily reduce appetite and slow gastric emptying.

• Early clinical studies have shown promising effects on metabolic health and weight management.

• The treatment is currently in the early stages of development, and a Phase 2 clinical trial is planned to further evaluate its safety and effectiveness.

A newly developed pill could offer a fresh approach to treating type 2 diabetes and obesity. Early research suggests it may help lower blood sugar and increase fat burning without reducing appetite or causing muscle loss, two common concerns associated with some current weight loss medications.

The findings, published in the journal Cell, come from researchers at Karolinska Institutet and Stockholm University.

A Different Approach From GLP-1 Drugs

Unlike popular GLP-1 medications such as Ozempic, which are delivered by injection and work by influencing appetite signals between the gut and brain, the new treatment takes a completely different path.

Instead of targeting hunger, the experimental drug activates metabolism inside skeletal muscle. Researchers say this approach improved blood sugar regulation and body composition in animal studies while avoiding several side effects often linked to GLP-1 therapies, including appetite suppression, muscle loss, and digestive issues.

The treatment is taken as a tablet rather than an injection.

Early Human Trial Shows Promising Results

The researchers also conducted an initial Phase I clinical trial involving 48 healthy volunteers and 25 people with type 2 diabetes. According to the study, participants tolerated 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.

Designed to Boost Muscle Metabolism

The drug is built around a laboratory-developed molecule known as a β2 agonist. Researchers engineered the compound to activate important signaling pathways in a new way that benefits muscle tissue without excessively stimulating the heart, a challenge that has historically limited the use of 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.

Potential to Work Alone or With Existing Drugs

Because the new treatment works differently from GLP-1 medications, researchers believe it could be useful both on its own and alongside existing therapies.

"This makes them valuable both as a stand-alone treatment and in combination with GLP-1 drugs," says Shane C. Wright.

The next step will be a larger Phase II clinical trial led by Atrogi AB, the company developing the drug. Researchers hope to determine whether the benefits observed in preclinical studies can be replicated in people living with type 2 diabetes or obesity.

Reference:

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. 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