Innovative new treatment for obesity will reduce impact of diabetes: is the ‘exercise pill’ just around the corner?
The number of adults around the world with diabetes quadrupled from 108 million in 1980 to 422 million in 2014. About 90 % of these people have type 2 diabetes (T2D) - a major cause of kidney failure, blindness, nerve damage, amputations, heart attack and stroke. It is estimated that only around 10 % of type 2 diabetics reach the goal of living a complication-free life. Current treatment of T2D either stimulates insulin production in pancreatic β-cells (GLP-1 receptor agonist) or blocks reuptake of glucose in the kidney, so glucose ends up in urine (SGLT2 inhibitors). When the pressure on the β-cells becomes too high to produce more insulin and these treatments fail, the last stage is to take injections of insulin. “Currently there is no approved drug that can increase glucose uptake in muscle (the main job of insulin) or reduce systemic insulin resistance that will relieve the pressure on β-cells. O304 can do all these things,” says the AMPK-DIAB (A small molecule AMP activated protein kinase (AMPK) activator, denoted O304, as a novel innovative drug for the treatment of type 2 diabetes) project coordinator Dr Thomas Edlund. O304 is one of the O-series of AMPK activator compounds. Dr Edlund explains that exercise causes energy levels to drop in cells. To restore energy levels, the enzyme AMPK is activated. AMPK activation increases uptake of glucose and lipids and stimulates the oxidation of these nutrients to generate energy, along with increasing blood flow to supply tissue with these nutrients. So the ability to activate AMPK with a drug-like, small molecule is the holy grail: it would give rise to the ‘exercise pill’. “Basically, this is exactly what we have achieved,” says Dr Edlund. “O304 mimics all the beneficial effects of exercise on obesity, T2D, fatty liver, the cardiovascular system and many other physiological functions. Animals that are treated with O304 actually run for much longer distances than control animals.” O304 can now be developed to treat obesity and associated diseases and complications, and he explains that it is safe and well-tolerated in both animals and humans. As it increases energy expenditure in animals by a novel, unique mechanism which results in the animals losing fat mass while eating even more, O304 is extremely well-suited to treating the global epidemic of obesity. No other drug on the market can increase energy expenditure. Betagenon, the Swedish company behind the AMPK-DIAB project, is hoping to target a high-risk population of T2D patients. “The main problem with T2D is the devastating complications, which to a large extent are caused by reduced blood flow in the tiny capillaries. O304 potently increases blood flow so it can address these complications in obese T2D patients,” he explains. They have successfully completed an exploratory 28-day, Phase IIa clinical trial in patients with T2D, currently on metformin, and are now conducting target product profiles, from a commercial perspective, for each disease for which O304 could be an option. “Diabetes is an epidemic that threatens the economies of all EU Member States. Our project addresses this challenge by delivering a novel drug treatment regimen to clinicians and their patients. O304 will fill the knowledge gap at an EU-wide level. To date, no company has been able to pre-validate an efficient small molecule AMPK activator,” says Dr Edlund.
Keywords
AMPK-DIAB, diabetes, Betagenon, O304, AMPK activator compounds, exercise pill, obesity