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Diet Pill Acomplia Keeps the Pounds Off
Study Adds to Favorable Research for Experimental Diet Drug
By Peggy Peck
March 8, 2005 (Orlando) - The experimental diet drug Acomplia helps keep off unwanted pounds for up to two years, new research shows.
After two years of treatment, patients in the study maintained a 16-pound weight loss. More than a third of patients taking the drug lost 10% of their body weight.
The drug targets a pleasure center in the brain that researchers believe is linked to overeating and other behaviors such as smoking. This new research is the fourth positive study of the drug, showing that Acomplia can take off pounds and help people stop smoking.Acomplia can take off pounds and help people stop smoking.
Luc Van Gaal, MD, studied more than 1,500 overweight adults in a two-year study. He reported the findings at the American College of Cardiology 2005 Scientific Session. The study was funded by Sanofi-Aventis, a Paris-based pharmaceutical company that has been developing the drug for clinical use.
In November 2004, Douglas Greene, MD, vice president of corporate medical and regulatory affairs for Sanofi-Aventis, told WebMD that the company planned to file for approval with the FDA in the second quarter of 2005.
"We can now say that we have robust data that can be replicated that shows [Acomplia] helps people lose weight and maintain that weight loss,shows [Acomplia] helps people lose weight and maintain that weight loss," says Van Gaal, who is a professor of diabetology, metabolism, and clinical nutrition at the University of Antwerp in Belgium.
Participants in the study were randomly selected to take either low-dose Acomplia (5 mg), high-dose Acomplia (20 mg), or a placebo. Additionally, all patients were told to reduce their daily caloric intake by 600 calories. They were not given any specific dietary guidelines, nor were they given exercise recommendations.
After two years, the patients taking 20 mg lost an average of 16 pounds and kept the weight off. The patients taking lower dose Acomplia lost an average of 10 pounds. Patients taking a placebo lost an average of 5.5 pounds.
Perhaps even more encouraging, says Van Gaal, is that the patients taking Acomplia dropped inches from their waist, which is especially significant since expanding waistlines are associated with increased risk of heart disease and diabetes.expanding waistlines are associated with increased risk of heart disease and diabetes.
Van Gaal says that it looks like each 2.2 pounds of weight lost takes an inch off the waist. The average waist reduction was 3 inches for patients taking 20 mg and 1.3 inches for those on the lower dose.
After the first year of treatment, 39% of patients taking high-dose Acomplia were able to reach a goal of losing 10% of their weight. After two years, 32% of the high-dose patients maintained that level of weight loss.
This is very encouraging, says Van Gaal, because "people always say they want to lose 40 pounds, but you can achieve real health benefits by losing 10% of your body weight. This is a realistic and sustainable goal." He says other studies have reported that patients who hit the 10% goal cut their risk of developing diabetes in half.
Julius Gardin, MD, chief of cardiology at St. John Hospital in Detroit, says, "The question is that we know that the battle against obesity is more than just a two-year fight. We would like to see if this weight reduction is maintained long term." Gardin was not involved in the Acomplia study.
"CB1 blockade with rimonabant 20 mg, combined with a hypocaloric diet over one year, promoted significant decrease of body weight and waist circumference, and improvement in cardiovascular risk factors," the authors write. "The large number of patients treated with CB1 blockade who achieved the 10% target for weight loss or had a marked improvement in the top risk factors established by the world-wide INTERHEART study, suggests that rimonabant can be considered as a valuable adjunct therapy for weight and waist reduction in patients at high cardiovascular risk."
Sanofi-Aventis, maker of rimonabant, funded the study and provided honoraria to five of the authors.
In an accompanying comment, Uberto Pagotto, MD, and Renato Pasquali, MD, from Sant Orsola-Malpighi General Hospital in Bologna, Italy, note that these findings suggest a weight-independent effect of rimonabant on lipid parameters. Whether the mechanism is related to a rise in adiponectin or other mechanisms is still unknown.
"These data, and those from the other ongoing clinical trials with rimonabant, might presumably help us to better tackle obesity and related metabolic and cardiovascular disease," Drs. Pagotto and Pasquali write. "When additional drugs are available, we will also have the possibility to individually target the therapeutic strategies according to phenotype characteristics and to the pathophysiological mechanism inducing the disease."
Dr. Pagotto has financial arrangements with Sanofi-Aventis, Abbott, Eli Lilly, and the European Commission. Dr. Pasquali has received honoraria, speaker's fees, and research grants from Sanofi-Aventis, Abbott, and Roche.
As research yields new data on the complex metabolic underpinnings of obesity, the promise of new agents to fight this problem grows. Cannabinoid receptors have been found in a wide variety of human tissue, and overactivation of the endocannabinoid system appears to contribute to obesity.
Rimonabant represents a new class of CB1 antagonist, and it appears to target multiple organs. It may exert an anorexic effect on the central nervous system while also acting on the gut to increase the sensation of satiety. In addition, this drug may inhibit lipogenesis within adipose tissue and promote glucose uptake into skeletal muscle.
The authors of the current study compare rimonabant with placebo in a double-blind trial that examines not only weight but metabolic factors as well.
Adults with a BMI of 30 kg/m2 or more or 27 kg/m2 or more with either hypertension or dyslipidemia were recruited from multiple centers in Europe and North America for study participation. Participants were generally healthy. Patients with diabetes, depression, or who were using medications that might affect weight were excluded from the trial. After a 2-week screening period and 4-week run-in period, subjects were randomized to receive rimonabant at a dose of 5 or 20 mg per day or matching placebo. All study subjects received counseling on diet and exercise to encourage weight loss. The main study outcome was the change in body weight following 1 year of treatment. Secondary outcomes included waist circumference, blood pressure, lipid values, and measures of glucose tolerance at 1 year. All analyses reported were based on an intent- to-treat model. 309 men and 1,198 women underwent randomization, and 61% of subjects completed the 1-year trial. Baseline characteristics were similar between treatment groups. The mean patient age was 45 years old, and the mean BMI was 36 kg/m2. The average weight was 100 kg, and the mean waist circumference was 108 cm. The mean weight loss at 1 year from baseline was 1.8, 3.4, and 6.6 kg in the placebo, 5-mg rimonabant, and 20-mg rimonabant groups, respectively. The improvements in both rimonabant groups were statistically significant when compared with placebo. The respective decreases in waist circumference were 2.4, 3.9, and 6.5 cm, another significant difference for both active treatments vs placebo. Both rimonabant groups had significantly more subjects reporting weight loss of more than 5% of baseline weight vs placebo. More than half of subjects receiving rimonabant, 20 mg, lost this amount of weight, and 27.4% of this cohort lost at least 10% of baseline weight. There was no significant difference between placebo and rimonabant, 5 or 20 mg, in the effect on blood pressure. Rimonabant, 5 and 20 mg, was associated with a significant increase in HDL cholesterol compared with placebo, but only the 20-mg strength significantly improved triglyceride values and total/HDL cholesterol ratios. Low-density lipoprotein cholesterol rose slightly in all groups. Rimonabant, 20 mg, but not 5 mg, significantly reduced fasting glucose and fasting insulin levels and a measure of insulin resistance compared with placebo at 1 year. Impaired glucose tolerance as measured by an oral glucose tolerance test was not significantly affected by rimonabant therapy. The prevalence of metabolic syndrome decreased by 21.3%, 30.6%, and 53.6% in the placebo, 5-mg rimonabant, and 20-mg rimonabant groups, respectively. This difference was statistically significant between the rimonabant, 20 mg, cohort and the placebo group. Rates of serious adverse events were similar across groups, with psychiatric disorders reported more frequently in the 20-mg rimonabant group (1.5% vs 0.3% in both the 5-mg rimonabant and placebo groups). Discontinuation rates due to adverse events were higher in the 20-mg rimonabant (14.5%) than in the 5-mg rimonabant group (8.3%) and placebo group (9.2%). Depressed mood was the most common reason for study discontinuation due to adverse events in all treatment groups. However, for the entire cohort, measures of anxiety and depression at 1 year were static vs baseline values and were similar in all treatment groups.
