TUESDAY, Nov. 9, 2004 (HealthDayNews) -- The biggest trial to date on an experimental obesity drug shows the pill is both safe and effective, researchers say.
Individuals taking a higher dose of rimonabant (brand name Acomplia) managed to sustain a weight loss of almost 20 pounds over two years.
"This seems to be an encouraging drug with respect to weight loss, particularly central fat weight loss," said lead investigator Dr. F. Xavier Pi-Sunyer.
"It is also encouraging that this is a broader-effect drug in the sense that it also hits other risk factors for cardiovascular diseases. There is an independent effect of this drug on HDL ["good"] cholesterol, triglycerides and on insulin resistance over and above weight loss," said Pi-Sunyer, who is with St. Luke's/Roosevelt Hospital Center, Columbia University in New York City.
"It's a drug that is targeting a different system than any weight-loss drug has targeted before," he added.
Pi-Sunyer presented the results Tuesday at the American Heart Association's scientific sessions in New Orleans.
Rimonabant is also being tested as a way to help smokers quit the habit.
Obesity, an important risk factor for cardiovascular disease, has become epidemic in the United States and other parts of the world. An estimated 60 percent of Americans are either obese or overweight. Effective treatments for the condition have been elusive, making an obesity pill a long sought-after goal.
Rimonabant is the first of a new class of drugs called selective CB1 blockers, which block the endocannabinoid (EC) system, one of the body's "pleasure centers."
Two previous trials have reported weight loss, as well as improvements in cardiovascular risk factors. This study is the largest of the three, however, and presents longer-term data.
For this trial, 3,040 patients, about 80 percent of them women, were randomly chosen to receive either 5 milligrams of rimonabant, 20 milligrams of the drug or a placebo. The participants, from the United States and Canada, had to have a body mass index (BMI) of 30 or more, or a BMI of 27 with an existing disease to qualify for the trial. The mean age was 45 and the average waist circumference was 42 inches. All participants, including those in the placebo group, were assigned reduced-calorie diets as well.
While there was some success with the 5 milligram dose, the 20 milligram dose seemed to be the one with the most significant effect.
"Participants [on 20 milligrams of rimonabant] achieved and maintained a weight loss of 19 pounds vs. 5.1 pounds in the control group," Pi-Sunyer reported. Almost two-thirds (62.5 percent) lost more than 5 percent of their body weight vs. 33 percent doing diet alone. Almost one-third (32 percent) lost more than 10 percent of their body weight on the drug vs. 16 percent for the placebo group. At two years, those on rimonabant lost 3.1 inches from their waist vs. 1.5 inches in the control group.
What's more, levels of HDL cholesterol increased by 24.5 percent; triglycerides -- blood fats -- were reduced by 9.9 percent, compared with 1.6 percent in the placebo group; and insulin sensitivity improved. The improvements in cholesterol, triglycerides and insulin sensitivity were only partially attributable to the weight loss.
"There was a 50-50 effect," Pi-Sunyer said. "We're getting a kind of double whammy. One is related to weight loss and central fat decrease and the other is an independent effect of the drug."
The drug's overall safety was good, with a slightly higher incidence of depression, anxiety and irritability in the 20 milligram group vs. the placebo group. The 20 milligram group also experienced more nausea. A depression scale, however, showed no difference between the two dosages and the placebo. "There was no evidence that this drug in two years had something we have to worry about in regard to safety," Pi-Sunyer said.
Researchers envision using this drug as a long-term treatment. "Clearly, we consider obesity to be a chronic problem," Pi-Sunyer said. "You don't cure obesity. You just improve it. It's not different from hypertension or diabetes or high cholesterol."
Individuals who lost weight on the drug then stopped taking it after one year regained the weight. Those who stayed on the drug maintained their weight loss through the second year, Pi-Sunyer said.
Pi-Sunyer estimated that the maker of rimonabant, Sanofi-Synthelabo, would file for U.S. Food and Drug Administration approval sometime in 2005.
The U.S. Centers for Disease Control and Prevention has more on overweight and obesity.