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A novel oral metabolic drug that targets skeletal muscle — rather than suppressing appetite — is advancing toward larger clinical trials after encouraging preclinical and phase I results. Early data suggest improved blood sugar control and greater fat loss while preserving lean mass, offering a potential alternative to injectable GLP-1 drugs such as Ozempic.
Muscle-first strategy: a different route to metabolic health
Instead of acting on gut–brain appetite circuits, this experimental compound is designed to act directly on skeletal muscle. Built around a lab-engineered β2 agonist scaffold, the molecule selectively redirects cellular signaling to increase glucose uptake and mitochondrial metabolism in muscle cells. The result in animal models was improved glycemic control and a shift in body composition toward less fat but maintained — even increased — lean mass.
How it differs from GLP-1 treatments
GLP-1 receptor agonists such as Ozempic and Wegovy lower body weight largely by reducing appetite and slowing gastric emptying. They are effective but commonly cause sustained loss of appetite, gastrointestinal side effects, and in some cases unwelcome reductions in muscle mass. By contrast, a muscle-targeted oral agent aims to burn stored fat while sparing the muscle that’s crucial for resting metabolism and long-term health.
What the studies found: safety signals and metabolic effects
Preclinical studies reported two key benefits: better glucose control and improved body composition. In animals, the compound reduced fat stores without the muscle wasting seen with some weight-loss strategies. Importantly, the molecule was engineered to avoid the strong cardiac stimulation associated with older β2 agonists, lowering potential heart-related risks.
When used alongside GLP-1 therapy in animal models, this muscle-directed drug mitigated the muscle loss that can accompany incretin-based weight-loss medicines — suggesting a complementary role rather than a competing one.
Early human testing
A phase I trial enrolled 48 healthy volunteers and 25 people with type 2 diabetes. According to researchers, the tablet was generally well tolerated and demonstrated pharmacokinetic properties consistent with once-daily oral dosing. Those initial human data align with the preclinical promise and justify moving into larger efficacy trials.
Why preserving muscle matters
Muscle mass is not merely about strength or appearance — it’s a major site for glucose disposal and a regulator of basal metabolic rate. Loss of lean mass in diabetes and obesity is linked to worse metabolic outcomes and can reduce life expectancy. By protecting or enhancing skeletal muscle while promoting fat loss, this approach tackles both glycemia and body composition.
Next steps: phase II and clinical prospects
Biotech company Atrogi AB plans a larger phase II study to test whether the benefits seen in animals and in phase I hold true in people living with type 2 diabetes or obesity. Researchers describe the compound as usable both as a standalone oral therapy and in combination with GLP-1 drugs, because the mechanisms are complementary.
"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.
"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," adds Shane C. Wright, assistant professor at the Department of Physiology and Pharmacology, Karolinska Institutet.
Potential risks, limitations and research questions
No drug is without trade-offs. Although early results report fewer cardiac effects than classic β2 agonists, long-term cardiovascular safety must be demonstrated in larger human cohorts. Other questions include how the drug performs across diverse patient groups, whether benefits persist long-term, and how best to combine it with existing therapies like GLP-1 agonists.
Expert Insight
"A pill that selectively boosts muscle metabolism could change how we treat metabolic disease," says Dr. Emily Harris, endocrinologist and clinical researcher. "If phase II confirms both safety and durable improvements in body composition, clinicians will have a new tool that complements GLP-1 therapies — particularly for patients who experience muscle loss or cannot tolerate injections."
Beyond a single mechanism, this development highlights a broader trend in metabolic medicine: precision-targeted drugs that aim to maximize benefit while minimizing systemic side effects. The upcoming phase II trial will be decisive in determining whether this muscle-focused strategy can move from promising science to standard clinical practice.
Source: scitechdaily
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