Researchers have developed an oral medication that tackles type 2 diabetes and obesity through a fundamentally different mechanism than the injection drugs that have dominated the market in recent years. Early testing suggests the pill can lower blood sugar and boost fat burning while preserving muscle mass, a significant advantage over existing therapies.
The work, published in Cell by scientists at Karolinska Institutet and Stockholm University, represents a shift away from appetite suppression. Instead of making people feel full, the experimental drug activates metabolism directly in skeletal muscle tissue, potentially avoiding the side effects that have plagued GLP-1 medications like Ozempic.
The team tested the compound in a Phase I trial involving 48 healthy volunteers and 25 people with type 2 diabetes. Participants tolerated the treatment well, offering early encouragement for moving forward. Tore Bengtsson, a professor at Stockholm University's Department of Molecular Bioscience, noted the significance of preserving muscle. "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."
GLP-1 drugs like Ozempic and Wegovy work by sending appetite-suppressing signals from the gut to the brain. They require weekly injections and can cause muscle wasting, constipation, and other gastrointestinal problems. The new pill takes an entirely different route. It uses a laboratory-engineered molecule called a β2 agonist, designed to stimulate metabolic pathways in muscle tissue without overstimulating the heart, a problem that has historically limited this class of drugs.
Because the mechanism is distinct from GLP-1 therapy, researchers believe it could stand alone or work alongside existing medications. Shane C. Wright, an assistant professor at Karolinska Institutet and one of the study's lead researchers, said the potential for combination use opens strategic possibilities. "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."
The next phase is a larger Phase II clinical trial led by Atrogi AB, the company developing the drug. That study will test whether the benefits seen in animals and the initial human safety trial actually translate to meaningful weight loss and glucose control in people with the conditions the drug is meant to treat.
The research involved collaboration across six universities and research institutions in Sweden, Denmark, and Australia. Multiple funding bodies supported the work, including the Swedish Research Council and the Novo Nordisk Foundation. Several of the study's authors work for or hold equity in Atrogi AB, and Bengtsson serves as the company's founder and chief scientific officer.
Author Jessica Williams: "A pill that avoids the appetite-suppression trap and preserves muscle could genuinely change the game if Phase II data holds up, but we're still early and the bar for something better than Ozempic is extraordinarily high."
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