Obesity researchers study drug cocktails
By Stephen Smith, Globe Staff | October 23, 2006
Obesity researchers are testing whether pills taken in combination can shrink the nation's bulging waistline and reduce deadly complications of the disease, just as powerful drug cocktails transformed the AIDS epidemic.
A scientists' meeting yesterday in Boston revealed findings of small-scale studies that suggest existing drugs used to treat depression and seizures may hold promise for reducing weight when taken together.
There is no disputing the urgent need for new approaches to controlling obesity: Nearly two-thirds of American adults weigh too much, and obesity is linked to a host of other medical conditions, including heart disease, diabetes, and cancer.
Anti obesity drugs currently on the market have had limited success, in part because of side effects and because they result in relatively modest weight loss. Scientists said they hope that by combining pills, they would be able to maximize the benefits of medicines, and potentially limit their toxicity by giving them in smaller doses.
"It has a lot of appeal to physicians because the way we treat so many chronic conditions is with more than one drug," said Dr. Donna Ryan, chairwoman of the obesity researchers' conference, which has drawn 2,100 participants to Boston and will conclude tomorrow. "It's a direction we're moving in with obesity, but we're not there yet."
Until two decades ago, obesity was viewed more as a failure of character than as a medical condition rooted in human biology. But as the biochemical underpinnings of the condition became clearer, the hunt for ways to address it intensified.
There are only two drugs on the market designated for long-term weight control: orlistat and sibutramine. Both have side effects.
In a lecture to physicians on Saturday, Dr. David Arterburn of Seattle described the intestinal complications experienced by some patients taking orlistat, marketed as Xenical. And he said that because sibutramine may increase blood pressure, it is not a good option for patients with cardiovascular conditions, which are common among the obese.
Researchers around the world are looking for new compounds to control weight. "The general take on things is that there are 50 to 100 compounds in various stages of development," said Arterburn, an internist.
Other scientists are examining whether it is feasible to treat obesity using medicines originally intended for different conditions, and to use them in combination. That strategy has revolutionized the treatment of other complex diseases, including AIDS, diabetes, and high blood pressure.
The premise for combining drugs is much the same whether for HIV or obesity: Attack the disease on multiple fronts, rather than aim at a single target.
That is especially critical when it comes to obesity, because the brain has figured out ways to outsmart single drugs. This is why most people taking existing pills see their weight loss plateau after about six months, said Dr. Kishore Gadde, a Duke University obesity researcher.
"Once you have lost about 10 percent, the brain panics and it resets itself," Gadde said. "Whether a normal-weight person is losing weight or an overweight person is losing weight, the brain responds the same: It is sensing you are in trouble."
Gadde was one of two scientists who presented findings yesterday of pharmaceutical company-sponsored trials that tested cocktails of drugs that caused incidental weight loss in patients taking them for other reasons.
In his study, Gadde used low doses of a seizure medication called topiramate as well as a common obesity pill, phentermine, which is usually recommended only for short-term use.
The study, which lasted six months and started with 200 patients, found that participants who took the drug combination lost an average 11.4 percent of their body weight. That was more than patients who took just one pill, or those who took a placebo .
On average, patients taking the two drugs in combination shed more than 20 pounds after six months. Researchers said side effects were mild, with a condition that causes a burning sensation the most frequent.
In a separate study, scientists used two other drugs: bupropion, typically prescribed to treat depression and to help people stop smoking, and zonisamide, which is used to treat seizures.
The study participants who took both drugs lost, on average, 12 percent of their body weight after nearly a year, said Dr. Frank Greenway, of the Pennington Biomedical Research Center in Baton Rouge, La. A constellation of side effects was reported, including insomnia, nausea, and fatigue.
"The combination appeared to give greater weight loss than any of the currently approved drugs," Greenway said. "It gave enough encouraging information to take it forward to future trials."
Both of the drug combination studies involved a relatively small number of patients and neither lasted long enough to draw definitive conclusions, researchers said.
And scientists cautioned that when it comes to obesity drugs, the road from experiment to medicine cabinet could be lengthy , with the US Food and Drug Administration setting especially rigorous approval standards for the medications.
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