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March 7, 2012

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Fighting losing battle of the bulge

THE battle of the bulge has been a big, fat failure for US drugmakers. But that has not stopped them from trying.

For nearly a century, scientists have struggled to make a diet pill that promotes weight loss without side effects ranging from embarrassing digestive issues to dangerous heart problems.

Recently a government panel recommended the Food and Drug Administration approve the latest diet drug Qnexa. A decision is expected by mid-April.

Today's research focusses on medications blocking signals associated with food craving and appetite. Initially rejected due to risks of heart palpitations and other safety issues, Onexa is a combination of two older drugs.

It uses phentermine, the appetite suppressant. The other drug is topiramate, an anticonvulsant sold by Johnson & Johnson as Topamax. It makes patients feel more satiated, but it's unclear exactly how. Topamax was studied alone for weight loss but rejected because of significant psychiatric side effects, such as memory loss and difficulty concentrating.

The recommendation raises hopes that the US could approve the first anti-obesity drug in more than a decade. It also highlights how difficult it is to create a pill that works in a variety of people without negative side effects. Even Qnexa was previously rejected over concerns that it can cause heart palpitations and birth defects if taken by pregnant women.

"Having a drug for obesity would be like saying you had a drug for fever," says Dr Mitchell Roslin, chief of bariatric surgery at Northern Westchester Hospital in New York. "There can be millions of reasons for obesity; it's a symptom of underlying mechanisms."

An effective and safe diet pill would be an easy sale in the US where more than 75 million adults are obese, a rate of nearly 35 percent. But the biggest problem is that there appears no safe way to turn off one of the body's fundamental functions - storing calories.

For millions of years, humans have been programmed to consume calories and store them as energy, or fat. This biological mechanism makes it almost impossible to quickly lose weight by not eating. Cutting down on food instead sends stronger signals to the body to store more calories.

"Throughout most of human history calories were scarce and hard to get, so we have many natural defenses against starvation," says Dr David Katz of Yale University's Prevention Research Center. "We have no defenses against overeating-we never needed them."

So, the drug industry has been on a long search for a safe and effective diet pill. It has mostly failed and many experiments have been fatal.

The worst diet pill safety debacle came in the 1990s and involved the combination of phentermine and another weight loss drug marketed by Wyeth called fenfluramine. The combination, dubbed fen-phen, was never approved by the FDA but doctors wrote millions of separate prescriptions.

Studies suggested that up to a third of fen-phen patients experienced heart valve damage. In 1997, it was recalled and Wyeth paid more than US$13 billion to settle personal injury lawsuits.

Drugmakers are trying other concoctions. Currently, the only drug approved for long-term weight loss in the US is orlistat, sold as the prescription drug Xenical and over the counter as alli. It works by blocking absorption of fat, which is excreted.




 

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