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Weight-Loss Drug Falls Flat
Diet and exercise still the best prescription for dropping pounds

By Steven Reinberg
HealthDay Reporter

TUESDAY, Oct. 3 (HealthDay News) -- A once promising weight-loss drug that produced encouraging results in animal studies has failed to deliver in a real-world trial of humans and will be shelved, the pharmaceutical firm Merck & Co. announced Tuesday.

The drug, known as MK-0557, was designed to focus on a "hunger-stimulating factor," which has long been considered a potential target for anti-obesity therapy. And while the drug was well tolerated by the 832 obese people who finished the trial, they only lost an average of 7.5 pounds during the 12-month study, compared with people taking a placebo who lost an average of 4 pounds.

The report, the culmination of a 10-year study, was published in the October issue of Cell Metabolism.

"People did lose a statistically significant amount of weight, but not clinically meaningful," said lead researcher Dr. Steven B. Heymsfield, executive director of clinical sciences at Merck. "The weight loss was about 3 pounds above the placebo group, but that has no commercial viability for a drug company."

In animal experiments, the drug caused significant weight loss, Heymsfield said. "In humans, the drug also completely blocked the receptor," he said.

In the trial, 1,661 obese people were assigned to MK-0557 or a placebo. Of these, 832 completed the trial.

The upshot of the trial was that a receptor called NPY5R, while related to food intake, appears not to be a key player in regulating hunger. "Maybe it's not a main pathway," Heymsfield said. Another explanation might be that food intake is regulated by a number of pathways. "If one system shuts down, other systems compensate for it," he said.

One expert thinks that hoping for a magic pill is the wrong approach to weight loss.

"In my view, this trial suggests not that a cocktail of drugs will be needed, but that for the most part, drugs are not the right answer at all," said Dr. David L. Katz, an associate professor of public health and director of the Prevention Research Center at Yale University School of Medicine.

"Though rare case of obesity may warrant medication as part of a comprehensive treatment plan, the hope that drugs will save most of us the trouble of addressing weight control through lifestyle practices is misplaced," he said.

"The causes of epidemic obesity are all around us and largely modifiable whenever we muster the will," Katz said. "The relative failure of MK-0557 will perhaps encourage us to focus less on attempts to block receptors in our brains, and more on using our brains to unblock opportunities for more healthful eating and activity in the schools, work sites, and communities we frequent each day."

In a related report in the same issue of the journal, European researchers found that the notion of "whetting the appetite" -- think hors d'oeuvres -- may actually have a base in biology. In experiments with rats trained to a strict feeding regimen, brain activity in important hunger centers spiked with the first bites of food, the researchers said.

"The drive to eat is massively stimulated by the start of eating," researcher Gareth Leng, of the University of Edinburgh, said in a prepared statement. "This shows the appetizing effect of food itself as hunger circuits are acutely switched on."

Leng's group found that the expectation of food activated certain brain cells involved in triggering hunger. The rats' optimal window for consumption was brief, however. The reason: The brain centers responsible for registering the feeling of fullness switched on almost as soon as food hit their stomachs.

More information

The U.S. National Institute of Diabetes and Digestive and Kidney Diseases can tell you more about losing weight.



Copyright © 2002 ScoutNews, LLC. All rights reserved.

SOURCES: Steven B. Heymsfield, M.D., executive director, Clinical Sciences, Merck & Co., Whitehouse Station, N.J.; David L. Katz, M.D., M.P.H., associate professor, public health, director, Prevention Research Center, Yale University School of Medicine, New Haven, Conn., and author, Flavor Point Diet; October 2006 Cell Metabolism

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