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Diet Drug Helps Patients Maintain Lower Weight

>>Zeev- whats your opinion of Sanofi? This drug sounds very interesting<<

Sanofi Pill, Which Blocks
'Munchie' Receptor, Shows
Other Health Benefits, Too
By RON WINSLOW
Staff Reporter of THE WALL STREET JOURNAL
November 10, 2004; Page D13

NEW ORLEANS -- Researchers reported the first evidence that a highly anticipated experimental weight-loss drug not only helps people slim down, but helps them keep off the pounds for as long as two years.

In a study involving 3,045 people, those who stuck to a daily 20 milligram regimen of the drug, called rimonabant, lost an average of more than 17 pounds within the first year of treatment, and maintained their new weight for an additional year.

Those who lost the weight and then switched to a dummy pill gained nearly all of it back during the second year of the study.

"The sustained weight loss is a nice effect, which is unusual," said Xavier Pi-Sunyer, chief of endocrinology at St. Luke's-Roosevelt Hospital Center, New York, and principal investigator of the study. Normally in weight-loss studies of drugs and other strategies, people begin putting the pounds back on within a few months. Dr. Pi-Sunyer presented the findings -- the third major weight-loss study on the drug unveiled this year -- at the annual scientific meeting of the American Heart Association.

WEIGHTS AND MEASURES



Two-year impact for patients taking 20 milligram dose of rimonabant

Average Weight loss: 17.4 pounds
Average reduction in waist circumference: 3.2 inches
Participants who lost more than 5% of initial body weight: 62.5%
Participants who lost more than 10% of initial body weight: 32.8%
Average increase in good, HDL cholesterol: 24.5%
Average reduction in blood fats called triglycerides: 9.9%
Patients who dropped out of the study because of "adverse events" after first year: 12.8%
Additional dropouts after second year: 6.0%

Note: Trial also included patients taking 5 milligrams and a placebo, where benefits and risk of dropout were generally lower.

Source: Xavier Pi-Sunyer, St.Luke's Roosevelt Hospital Center, New York



Rimonabant, which is being developed by Sanofi-Aventis SA of Paris, is attracting wide interest not only for its weight-loss benefits, but because it appears to have positive effects on waist circumference, HDL (the "good cholesterol"), and blood sugar, all of which can factor into risk of diabetes and heart disease.

The drug blocks receptors in what is called the endocannabinoid system in the brain, which, among other things, is stimulated by cannabis, the active ingredient in marijuana. Researchers believe the receptors, which also reside in fat cells and in nerves in the stomach, play a critical role in regulating appetite.

A growing body of research also suggests that abdominal fat, as opposed to, say, fat in the thighs or buttocks, leads to elevated risk for heart disease. Researchers said some 44% of adult Americans have a waist circumference exceeding 40 inches in men and 35 inches in women, the threshold for high risk. In the current study, people who took the drug for two years lost an average of 3.2 inches around the waist, from an average of 41 inches. People on placebo lost an average of 1.5 inches from their waistlines. All study participants were on a reduced-calorie diet.

The study was sponsored by Sanofi-Aventis, which expects to file with the Food and Drug Administration by next year's second quarter. Approval of the drug may come by the end of 2005 or early 2006.

As in the two previous studies, the drug was also associated with improvement in HDL cholesterol levels and in the body's ability to manage insulin, and a reduction in harmful blood fats called triglycerides.

About 50% of the participants dropped out during the first year, spread evenly across placebo and treatment groups, reflecting usual attrition in diet and weight-loss studies, Dr. Pi-Sunyer said. Within that group, 7.2% of patients on placebo and 13% of patients taking 20 mg of rimonabant dropped out for adverse events that included depression, anxiety, irritability and nausea. But during the second year there weren't any important differences in side effects between the drug and placebo, Dr. Pi-Sunyer said.

Heart experts said the findings were encouraging and regarded the medicine as a potentially important tool in controlling weight and other risk factors. But they said healthy diets and exercise would remain crucial.

"The pill is a good partner to get the ball rolling," said Sidney Smith, past president of the AHA and a cardiologist at University of North Carolina at Chapel Hill. "But willingness to change behavior and diet will be essential to achieving goals."

He said more information is needed on why people apparently stopped losing weight during the first year of treatment, and why people couldn't keep it off without the medicine. Robert H. Eckel, an endocrinologist at University of Colorado Health Sciences Center, Denver, said that despite early indications that the drug is safe, more data are needed if patients will have to say on rimonabant for prolonged periods.

Write to Ron Winslow at [e-mail]1

URL for this article:
http://online.wsj.com/article/0,,SB110001590248968914,00.html