Potential New Oral Drug for Type 2 Diabetes and Obesity
A new oral medication could soon compete with well-known treatments like Ozempic for managing type 2 diabetes and obesity, based on a recent study. While it hasn’t been tested on humans yet, this compound might avoid some of the adverse effects seen with similar drugs.
This emerging drug targets the β2-adrenergic receptor (β2AR), differing from the well-known GLP-1 receptor agonists. Medications that act on β2AR are not entirely new; for instance, salbutamol (known as Ventolin) is often prescribed for asthma and chronic obstructive pulmonary disease.
Clenbuterol, although commonly associated with athletics as a performance enhancer, is also given for asthma in certain countries. However, the World Anti-Doping Agency has banned it due to its anabolic properties.
For years, researchers have been exploring how to leverage β2AR agonists for their benefits without triggering their negative side effects. These drugs can enhance glucose uptake in muscles and help burn fat, mimicking exercise; however, concerns remain about their risk to heart health.
The β2-adrenergic receptors in the body interact with G proteins. When activated for extended periods—such as through the use of β2AR drugs—these receptors can lead to cardiovascular complications.
“This can cause an increase in heart rate and blood pressure, and prolonged usage might result in increased heart weight and hypertrophy,” explained Shane Wright, a molecular biologist at the Karolinska Institute in Sweden.
However, researchers from the Karolinska Institute, Stockholm University, and Atrogi AB have developed a series of β2AR agonists that appear to mitigate the adverse effects of G protein activation. One of these candidates, referred to as ‘compound 15’, seems less likely to produce harmful side effects, although confirmation will come with further clinical trials.
Unlike GLP-1 receptor agonists like Ozempic, compound 15 doesn’t seem to suppress appetite or cause muscle loss, suggesting a potentially safer profile. Being an oral medication also makes it more appealing for users, compared to the need for injections.
“The aim was to focus on this specific action of the receptor in skeletal muscle rather than in the heart, aiding in glucose uptake and providing a beneficial way to lower blood glucose levels,” Wright remarked.
The new compound has shown promise in laboratory trials involving cells, male mice, rats, and even beagles. Phase 1 clinical trials have tested its safety in healthy individuals as well as those with type 2 diabetes.
According to the findings, “Lead candidates from this chemical series improved glucose tolerance in preclinical models of diabetes and obesity, while causing little to no adverse cardiac effects.” They also helped reverse muscle atrophy linked to GLP-1 medications.
Preliminary clinical evaluations indicate that this lead candidate is orally bioavailable and considered safe for both healthy subjects and individuals with type 2 diabetes, highlighting its therapeutic potential.
Before compound 15 or its variations can serve as alternatives to GLP-1 drugs, more testing—and perhaps a catchier name—will be essential. Ongoing Phase 2 trials aim to determine if the enhanced muscle growth and improved glucose regulation seen in animal studies also translate to humans.
A “well-tolerated GRK2-biased agonist offers significant therapeutic potential beyond addressing type 2 diabetes and obesity, including conditions like muscular dystrophy and sarcopenia,” the authors noted.
This research has been published in the journal Cell.
