A safe diet drug? Miracle pill is elusive

WASHINGTON -- The battle of the bulge has been a big failure for U.S. drugmakers. But that hasn't stopped them from trying.

For nearly a century, scientists have struggled to make a diet pill that helps people lose weight without side effects that range from embarrassing digestive issues to dangerous heart problems.

Earlier this week, a government panel recommended that the FDA approve the latest diet drug, Qnexa. The recommendation raises hopes that the United States could approve the first anti-obesity drug in more than a decade.

It also highlights how challenging it is to create a pill that fights fat 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 in pregnant women.

"Having a drug for obesity would be like telling me you had a drug for the fever," said Dr. Mitchell Roslin, chief of bariatric surgery at upstate Northern Westchester Hospital. "There can be millions of different reasons why someone is obese."

An effective and safe diet pill would be an easy sale: With more than 75 million obese adults in the nation, the obesity rate is nearing 35 percent. But the biggest problem in creating a weight-loss drug is that there appears to be no safe way to turn off one of the human body's most fundamental functions.

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

So, the drug industry has been on a nearly 100-year search for a drug that can help the body shed pounds. It has mostly failed, sometimes with fatal results:

Early attempts focused on speeding up metabolism, or the body's method of breaking down food into energy. In the 1930s, doctors prescribed an industrial chemical called dinitrophenol, which accelerated metabolism, but also caused fever, swelling and deadly toxicity in some patients.

In the 1950s and '60s, amphetamines became popular drugs because they boost metabolism and suppress appetite. But the pills proved addictive, and doctors discovered they increase blood pressure and heart rate. The amphetamine phentermine is approved for short-term weight loss, usually less than 12 weeks, though it is seldom prescribed because of the potential for addiction.

Perhaps the worst diet pill safety debacle came in the 1990s and involved the combination of two weight-loss drugs, dubbed fen-phen. The combination was never approved by the FDA, but because the agency doesn't regulate doctors' decisions about prescribing various combinations of drugs, more than 18 million fen-phen prescriptions were written by 1996. One year later, studies suggested that up to a third of patients taking fen-phen experienced heart valve damage. In 1997, the maker of one of the drugs was forced to recall it and Wyeth was forced to recall two versions of fenfluramine and eventually paid more than $13 billion to settle tens of thousands of personal injury lawsuits.

In the past decade, drugmakers have moved toward other weight-loss concoctions. Currently, the only drug approved for long-term weight loss in the country is orlistat, which is sold as the prescription drug Xenical and over the counter as alli. The drug works by blocking the absorption of fat. When launched in 2007, alli received a high-profile marketing push from drugmaker GlaxoSmithKline, complete with TV ads and a celebrity endorsement by country singer Wynonna Judd. But it never took off due to unpleasant side effects, including loose bowel movements.