DIETING
January 12, 2015

The Perfect Diet Drug, Now in Trials

Fexaramine could be the diet drug we all have been waiting for: It tricks your body into thinking it has eaten.

It's the ultimate weight-loss solution: Feel full without eating anything.

Researchers from the Salk Institute have developed a new drug that tricks your body into thinking it has consumed calories, causing it to burn fat.

In the US, more than one-third of adults are obese, and diabetes has become an epidemic. Both conditions are associated with a number of health complications, raise healthcare costs, and significantly reduce average lifespans.

Additional tests also suggested that their overall metabolism was ramped up.

In animal models, the drug — fexaramine — was shown to stop weight gain, lower cholesterol, stabilize blood sugar and minimize inflammation in mice. Given the apparent benefits, clinical trials in humans have begun.

Contrary to other diet pills which are quickly absorbed into the blood, fexaramine remains in the intestines where it causes fewer side effects.

There, this “imaginary meal,” sends out the same signals that are relayed upon eating a large meal. The body responds accordingly, however no calories are actually consumed.

The research team has been investigating this pathway for decades, trying to understand how the body releases bile acids from the liver, digests foods, and stores fats or sugars. They found that eating a meal activates the bile acid sensor farnesoid X receptor (FXR).

Historically, pharmaceutical companies have targeted the FXR receptor in attempts to treat obesity, diabetes, liver disease and other metabolic conditions.

Drugs that have been developed so far affect multiple organs and come with many unwanted side effects. The possibility of modulating FXR solely in the intestine has, up until now, been impossible.

“When you eat, you have to quickly activate a series of responses all throughout the body,” Ronald Evans, director of Salk's Gene Expression Laboratory and senior author of the new paper, said in a statement. “And the reality is that the very first responder for all this is the intestine.”

Researchers gave obese mice a daily regimen of fexaramine for five weeks, demonstrating reductions in weight, body fat, blood sugar and cholesterol. Additional tests also suggested that their overall metabolism was ramped up.

But why does the drug work better when confined to the intestines (rather than the whole body)?

“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,” commented Evans. “We've learned how to trigger the first runner so that the rest of the events happen in a natural order.”

Fexaramine doesn’t reach the bloodstream, making it safer than other FXR-targeting drugs. Formal clinical studies in humans are needed to test its safety and effectiveness treating obesity and metabolic disease.

The study is published in Nature Medicine.

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