A drug that can be taken orally could soon rival the likes of Ozempic for treating type 2 diabetes and obesity, according to a new study. Although its efficacy hasn't yet been tested in humans, the compound could bypass some of the harmful side-effects associated with similar drugs.

Unlike the famous family of GLP-1 receptor agonist drugs, this new candidate targets the β2-adrenergic receptor (β2AR). Drugs that do this aren't new: salbutamol (sold as Ventolin among other brand names) is widely prescribed for use in short stints to treat asthma and chronic obstructive pulmonary disease.

Clenbuterol is also prescribed for asthma in some countries, though it's better known as a performance-enhancing drug, banned by the World Anti-Doping Agency for its anabolic effects.

For more than a decade, scientists have been trying to find a way to harness the benefits of β2AR agonists, without setting off their harmful effects. They can stimulate skeletal muscle glucose uptake and burn fat, mimicking the effects of exercise – but they have been considered too risky for treating diabetes or obesity, because of their tendency to wreak havoc on the heart.

Related: One Weight Loss Strategy Is 5x More Effective Than Ozempic, Trials Show

The body's β2-adrenergic receptors are coupled with G proteins, and when activated for long periods (by β2AR drugs, for instance), the G proteins set off a chain reaction which leads to cardiovascular problems.

"That would lead to heart rate increases, systolic blood pressure increases, and, eventually, that over-sustained exposure would lead to increases in heart weight and cardiac hypertrophy," molecular biologist Shane Wright, from Karolinska Institute in Sweden, told Mar de Miguel of Bioworld.

But a campaign led by scientists from the Karolinska Institute, Stockholm University, and the biotech company Atrogi AB has revealed a series of β2AR agonist molecules that can side-step the slippery slope triggered by the G proteins.

By activating only specific pathways, one of these – dubbed 'compound 15' – seems less likely to cause those concerning side effects, though we won't know for sure until further clinical trials are carried out.

Unlike GLP-1 receptor agonists like Ozempic, compound 15 doesn't suppress appetite or lead to muscle loss, which means it may be safer in that regard too. It's also much more user-friendly, as a drug that can be swallowed rather than injected.

"The goal was to try to target this other action that this receptor has expressed in the skeletal muscle, not in the heart, where it is mediating glucose uptake as a very beneficial outlet for lowering blood glucose levels," Wright said.

So far, the newly-designed drug has been tested in lab-grown cells, male mice, rats, beagles, and phase 1 clinical trials (which only test for safety, not efficacy) in healthy and type 2 diabetic men.

"Lead candidates of the chemical series increased glucose tolerance in preclinical models of diabetes and obesity with little or no increase in contractile force, cardiac lesions, and cardiac hypertrophy," the authors report. They also reversed muscle atrophy induced by GLP-1 drugs.

"Clinical evaluation demonstrated that our lead candidate was orally bioavailable and safe in both healthy volunteers and type 2 diabetics, underlining its therapeutic potential."

Many more tests – and a catchier name – will be needed before compound 15 or its relatives are made available as an alternative to GLP-1 drugs. Phase 2 clinical trials are underway to see if the enhanced muscle growth, balanced glucose levels, and insulin sensitivity seen in animal tests hold up in human bodies.

"A well-tolerated GRK2-biased agonist offers significant therapeutic potential beyond type 2 diabetes and obesity… like muscular dystrophy and sarcopenia," the authors add.

The research was published in Cell.