New Medication for Reducing Obesity(rimonabant) Shows Promise
Written by admin on August 22nd, 2007 in rimonabant study.
The World Health Organization estimates that more than 2.5 million deaths worldwide can be attributed to obesity each year, and the number continues to increase. Few safe and effective medications are available for obesity, but new understanding of the physiologic regulation of food intake and calorie storage have led to the development of therapies targeting the endocannabinoid system. This system is overactive in animal models of obesity and is believed to modulate food intake and adipogenesis through receptors (CB1) in the brain and a variety of peripheral tissues. Van Gaal and colleagues studied a CB1-blocking drug, rimonabant (Acomplia), in a large trial of adult obese patients.
The researchers recruited more than 1,500 obese adults from 60 European and U.S. centers. Inclusion criteria were a body mass index (BMI) of 30 or a BMI of 27 plus hypertension or dyslipidemia. Participants also were required to have experienced less than 11-lb (5-kg) variation in body weight in the three months before the study, and to be free from significant cardiovascular, pulmonary, hepatic, renal, neurologic, psychiatric, and endocrine disease, including diabetes. Participants were excluded if they had a history of surgical procedures for weight loss or of significant depression, were currently taking medications known to influence body weight, or intended to change their smoking status during the study period.
After extensive baseline assessment, including basal metabolic rate, body measurements, glucose tolerance testing, and other laboratory screening, 1,507 participants were randomly assigned to 5 mg per day of rimonabant, 20 mg per day of rimonabant, or placebo. All patients were advised on diet and exercise based on their personal basal metabolic rate. Patients were reassessed every 14 days for one month, then every 28 days for two years.
Patients in the three groups were comparable in all significant variables at baseline. Only 61 percent of participants completed the one-year follow-up: 379 (62.7 percent) in the 5-mg group, 363 (60.6 percent) in the 20-mg group, and 178 (58.4 percent) in the placebo group. Using intention-to-treat analysis, researchers found that patients taking rimonabant had significantly greater weight loss and improvement in lipids and insulin function after one year than those taking placebo. This effect was more pronounced if the analysis was limited to participants who completed one year of assigned therapy. In this analysis, the cumulative weight loss was 11 lb (5 kg) in the placebo group, compared with more than 22 lb (10 kg) in the 20-mg group. The percentage of patients with 10 percent or more weight loss was significantly greater in the 20-mg group (27.4 percent) than the placebo group (7.3 percent) but not in the 5-mg group (10.1 percent). If only those patients who completed the study were considered, these figures rose to 39 percent in the 20-mg group, 12.4 percent in the placebo group, and 15.3 percent in the 5-mg group. Waist circumference and lipid profile also improved significantly in patients taking rimonabant. The proportion of patients with metabolic syndrome decreased from 41.2 to 28.6 percent in those taking 5 mg and from 42.2 to 19.6 percent in those taking 20 mg, compared with a decrease from 39.9 to 31.4 percent in the placebo group. In about one half of participants, improvement in metabolic risk factors was independent of weight loss. Adverse effects were reported by more than 80 percent of patients in all three groups but most were mild and transitory. The greatest number of discontinuations (87) occurred in the 20-mg group, with almost one half (42) being attributed to psychiatric disturbance.
August 22nd, 2007 at 11:49 pm
Dr. James Anderson, who heads the UK College of Medicine Metabolic Research Group, supervised the studies of OTC-strength orlistat, or Alli. “Our research showed that people taking orlistat and following low-fat diets lost almost five percent of their initial body weight, about seven to 15 pounds, over four months,” said Anderson to the press.
Pronounced “ally,” as in friend, Alli may not be so friendly to some, however. Side effects can be quite startling, say both experts and users of Alli’s prescription-strength sister drug, Xenical. They included excessive flatulence, unexpected uncontrollable bowel movements, diarrhea, upset stomach, and loose, oily stool. The product’s information guide, Are You Losing It? Losing Weight Without Losing Your Mind, includes a recommendation that until users know how their bodies will respond to Alli, they would be wise to bring a change of clothing or wear dark-colored pants when leaving their homes.
Dr. John Husted, a bariatric surgeon at the California Pacific Medical Center, told The San Francisco Chronicle, “Long-term, I think people are going to be unsatisfied with this drug. People lose weight in different ways, and for some people it might work, but I expect that to be a minority of people.”
Some experts believe that an unintended result of the drug is to force people to choose lower-fat meals because of the unpleasant side effects of eating high-fat meals.
Some doctors who once prescribed Xenical, the stronger version of the drug, reported that their patients either did not return for prescription refills or only used Xenical for a short period of time, after which it seemed to lose its effectiveness.
In a related story, an FDA advisory committee voted unanimously yesterday to not recommend a different new diet drug, rimonabant, because of its potential side effects.
Though rimonabant has been marketed successfully in Europe, the committee voiced concerns that some patients could experience greater risk of depression and suicide. A U.S. News report stated that in clinical trials, patients taking rimonabant did lose significantly more weight than the control group, yet more than 25% of them reported side effects like increased depression and anxiety.