Feb. 17, 2004 — The drug rimonabant (Acomplia) is effective for weight loss and smoking cessation, according to a press conference held today by the drug's manufacturer.

"Those who stay on drug for a year show remarkable weight loss: 17 pounds," said Jean Pierre Despres, PhD, professor of food and nutrition sciences at Laval University in Montreal, Quebec, Canada. "And we saw a remarkable reduction in waist circumference of 8 cm."

Rimonabant acts like marijuana in reverse, cutting appetite and curbing the craving for nicotine in two large-scale clinical trials.

The drug has "roughly doubled the odds of quitting smoking," said Robert Anthenelli, MD, associate professor of psychiatry at the University of Cincinnati College of Medicine in Ohio. "We also found remarkably reduced postcessation weight gain: a 77% reduction versus placebo.... These dual effects on smoking cessation and reduced weight gain make rimonabant a promising agent for treating tobacco dependence."

The weight-loss study enrolled more than 1,000 moderately obese men and women. Half of them had metabolic syndrome.

After a year on a 600 Kcal/day diet, nearly 75% of participants who received 20-mg doses of rimonabant lost at least 5% of their body weight — and nearly half lost more than 10%. This is compared with about 25% of study participants who received placebo who lost more than 5% of their body weight. And only one in 10 lost more than 10% of their body weight.

That's impressive weight loss for any clinical trial. Plus, Dr. Despres said, people who took rimonabant lost abdominal fat. Half of those who had metabolic syndrome no longer had the condition after treatment.

"I am very impressed in the increase in HDL [high-density lipoprotein] cholesterol generated by this one-year rimonabant therapy," Dr. Despres said. "The 20-mg dose was able to generate a 20% increase in HDL, accompanied by more than a 10% decrease in triglycerides. Those who completed the full study had even more spectacular results: a 25% increase in HDL."

A second clinical trial tested whether rimonabant for smoking cessation. The 10-week trial enrolled nearly 800 men and women who smoked an average of 23 cigarettes a day before the study began. The goal was no smoking for at least four consecutive weeks.

Of those who completed the study, 36.2% of those who received a 20-mg dose of rimonabant quit smoking compared with about one fifth of those who received placebo.

None of these smokers were obese. But participants in the placebo group gained 6.6 pounds, while those in the rimonabant group gained only 1.5 pounds.

A one-year continuation of the trial is underway in the U.S. and Europe.

Rimonabant has been called the anti-marijuana. It blocks the CB-1 cannabinoid receptors, which are found on nerve and fat cells.

Douglas A. Greene, MD, vice president for regulatory affairs at Sanofi-Synthelabo, said that obese people and people with a craving for nicotine have an overactive cannabinoid system. By partially blocking this system, rimonabant helps people lose weight and quit smoking.

"This compound is completely novel," Dr. Greene said. "It is the first in a class of new medications that has effects on two major cardiovascular risk factors. These are probably the two major preventable risk factors for heart disease: smoking and obesity. This [drug] represents a major medical advance for patients at risk of heart disease."

Reviewed by Gary D. Vogin, MD