Progress towards an obesity pill

Researchers have developed a compound that causes the metabolism of mice to respond as if a meal has been eaten, so they burn fat to make room for new calories. Human trials could follow in the next few years.

Researchers from the Salk Institute for Biological Studies in California, USA, have developed a compound they describe as "an entirely new type" of pill that is able to prevent obesity in mice. Called fexaramine, it can stop weight gain, lower cholesterol and minimise inflammation.
Unlike most diet pills on the market, such as appetite suppressants or caffeine-based diet drugs, fexaramine won't dissolve into the blood. It remains within the intestines causing fewer side effects. It is so effective that researchers hope it can be fast-tracked for human trials within the next few years – perhaps by 2018, as predicted on our timeline.
“This pill is like an imaginary meal,” says Ronald Evans, director of Salk’s Gene Expression Laboratory and senior author of the study, which is published this week in Nature Medicine. “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.”


Evans’ laboratory has spent nearly two decades studying the 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. The body turns on FXR at the beginning of a meal to prepare for an influx of food. FXR not only triggers the release of bile acids for digestion – but also changes blood sugar levels and causes the body to burn some fats in preparation for the incoming meal.
Pharmaceutical companies aiming to treat obesity, diabetes, liver disease and other metabolic conditions have developed systemic drugs that activate the FXR protein, turning on many pathways that it controls. But these drugs affect several organs and come with all kinds of side effects. Evans’ team has shown that switching on FXR only in the intestines – rather than the intestines, liver, kidneys and adrenal glands all at once – can have a very different outcome.
“The body’s response to a meal is like a relay race, and if you tell all the runners to go at the same time, you’ll never pass the baton,” says Evans. “We’ve learned how to trigger the first runner so that the rest of the events happen in a natural order.”