Discovery: oral pill burns fat, controls diabetes and preserves muscles

Swedish researchers have developed an experimental oral medication that stimulates fat burning even at rest and improves glucose control without causing loss of muscle mass.

The compound, known asATR-258, acts directly on skeletal muscles through a selective mechanism on the beta-2 adrenergic receptor.

Initial results in animals and humans indicate the potential to treat obesity and type 2 diabetes with fewer cardiovascular risks than traditional treatments.

• The substance increases glucose uptake by muscles independently of insulin.
• Increases basal energy expenditure, reducing body fat.
• Preserves lean mass, unlike some GLP-1 agonists.
• Prevents overload on the heart by prioritizing specific metabolic pathways.

Innovative mechanism of action

ATR-258 represents a biased agonism approach at the beta-2 adrenergic receptor.

This strategy preferentially activates the GRK2 protein, responsible for signaling that favors muscle metabolism.

Unlike older agonists, which excessively increase cAMP and cause tachycardia, the new compound minimizes these effects.

Researchers at Instituto Karolinska and Universidade of Estocolmo tweaked the molecule to prioritize beneficial pathways in muscles.

Results observed in animals

In mice and rats with diet-induced obesity, ATR-258 treatment improved glucose tolerance.

The animals showed a significant reduction in body fat and an increase in energy expenditure at rest.

There was no cardiac hypertrophy or heart damage, even with prolonged use.

When combined with GLP-1 agonists, the compound prevented the muscle loss common in these treatments.

Initial human trials

The drug underwent a phase 1 clinical trial with healthy volunteers and patients with type 2 diabetes.

The pill demonstrated good oral absorption and a favorable safety profile.

There were no significant changes in blood pressure or heart rate.

Side effects were mild, with no signs of cardiovascular toxicity.

Advantages over current treatments

Current medications such as Ozempic and similar drugs require injections and can reduce muscle mass.

Traditional adrenergic drugs often cause heart problems.

ATR-258 offers oral administration and direct action on muscle metabolism.

This characteristic can facilitate adherence and allow therapeutic combinations for optimized results.

Next steps of the research

Company Atrogi plans to initiate phase 2 studies to evaluate efficacy in weight loss and glycemic control.

The tests will focus on body composition, muscle preservation and benefits over prolonged use.

Researchers intend to explore combinations with existing GLP-1 agonists.

Larger studies will confirm cardiovascular safety in broad populations.

The approach could pave the way for a new class of oral metabolic drugs.