Scientists have developed a new diet pill that could help people lose weight more effectively by tricking the body into thinking it has consumed a meal.
The compound effectively stopped weight gain, lowered cholesterol, controlled blood sugar and minimised inflammation in mice, making it an excellent candidate for a rapid transition into human clinical trials.
Unlike most diet pills on the market, this new pill, called fexaramine, does not dissolve into the blood like appetite suppressants or caffeine-based diet drugs, but remains in the intestines, causing fewer side effects.
"This pill is like an imaginary meal," said Ronald Evans, from the Salk Institute for Biological Studies.
"It sends out the same signals that normally happen when you eat a lot of food, so the body starts clearing out space to store it. But there are no calories and no change in appetite," said Evans.
Evans and his colleagues developed the fexaramine compound by departing from the drug scaffold that most pharmaceutical companies typically pursue when targeting farensoid X receptor (FXR), a protein that plays a role in how the body releases bile acids from the liver, digests food and stores fats and sugars.
"It turns out that when we administer this orally, it only acts in the gut," said Michael Downes, a senior staff scientist at Salk and co-corresponding author of the research.
Giving one such drug in a daily pill form that only reaches the intestines – without transporting into the bloodstream that would carry the drug throughout the body – not only curtails side effects but also made the compound better at stopping weight gain.
When the group gave obese mice a daily pill of fexaramine for five weeks, the mice stopped gaining weight, lost fat and had lower blood sugar and cholesterol levels than untreated mice.
In addition, the mice had a rise in body temperature – which signals metabolism ramping up – and some deposits of white fat in their bodies converted into a healthier, energy-burning beige form of the tissue.
Even the collection of bacteria in the guts of mice shifted when they received the drug, although what those changes mean is not clear yet.
Since fexaramine does not reach the bloodstream, it is also likely safer in humans than other FXR-targeting drugs, the researchers said.
They are already working to set up human clinical trials to test the effectiveness of fexaramine to treat obesity and metabolic disease.
The study was published in the journal Nature Medicine.