Medication Shows Modest Benefit In Reducing Weight, Improving HDL, Triglyceride Levels

Approximately two-thirds of U.S. adults are overweight or obese, which greatly increases the risk of developing diabetes mellitus and cardiovascular disease and death from related causes. Researchers believe that besides weight loss, obesity management should target improvement in certain cardiometabolic risk factors, which include abnormal cholesterol and glucose (blood sugar) levels and excess weight around the waist, according to background information in the article. Long-term weight management remains a challenge for patients and clinicians.

F. Xavier Pi-Sunyer, M.D., of St. Luke's-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, and colleagues evaluated the efficacy and safety of the weight-loss medication rimonabant in conjunction with diet and exercise in promoting reductions in body weight and waist circumference, long-term weight maintenance, and reduction of cardiometabolic risk factors in obese and higher risk overweight patients. The randomized, double-blind, placebo-controlled study, conducted from August 2001 to April 2004, included 3,045 adults who were obese (body mass index 30 or greater) or overweight (body mass index greater than 27 and treated or untreated hypertension [high blood pressure] or dyslipidemia [abnormal levels of certain lipids and lipoproteins in the blood]). Patients were randomized to receive placebo, 5 mg/d of rimonabant, or 20 mg/d of rimonabant for 1 year. Rimonabant-treated patients were re-randomized to receive placebo or continued to receive the same rimonabant dose while the placebo group continued to receive placebo during year 2.

Year 1 of the study was completed by 51 percent of patients in the placebo group, 51 percent in the 5 mg of rimonabant group, and 55 percent in the 20 mg of rimonabant group. After randomization, weight loss from baseline to 1-year was significantly greater in patients receiving 20 mg or 5 mg of rimonabant than in patients receiving placebo. The percentage of patients achieving a 5 percent or greater weight loss at 1-year was 26.1 percent for patients receiving 5 mg of rimonabant, 48.6 percent for patients receiving 20 mg of rimonabant, and 20.0 percent for patients receiving placebo. Compared with the placebo group, the 20 mg of rimonabant group produced greater average reductions in weight, waist circumference, and level of triglycerides and a greater increase in level of high-density lipoprotein (HDL) cholesterol.

Patients who were switched from the 20 mg of rimonabant group to the placebo group during year 2 experienced weight regain while those who continued to receive 20 mg of rimonabant maintained their weight loss and favorable changes in cardiometabolic risk factors. Rimonabant was generally well tolerated; the most common drug-related adverse event was nausea (11.2 percent for the 20 mg of rimonabant group vs. 5.8 percent for the placebo group).

"It must be acknowledged that the trial was limited by a high dropout rate and that long-term effects of the drug require further study. Still, our observations collectively suggest that rimonabant may well represent an innovative approach to the management of multiple cardiometabolic risk factors, facilitating and maintaining improvements through weight loss-dependent and -independent pathways," the authors conclude.

Editorial: Obesity Research--Limitations of Methods, Measurements, and Medications

In an accompanying editorial, Denise G. Simons-Morton, M.D., Ph.D., Eva Obarzanek, Ph.D., M.P.H., R.D., and Jeffrey A. Cutler, M.D., M.P.H., of the National Heart, Lung, and Blood Institute, Bethesda, Md., comment on the findings of Pi-Sunyer et al.

"Medications, diets, and lifestyle interventions all may have a role for high-risk patients in clinical practice but more research is needed on the effectiveness of diet and lifestyle interventions actually delivered in practice, as well as on the long-term efficacy and safety of medications. In addition to interventions aimed at individual patients, there is a need for a much broader spectrum of approaches to address the widespread obesity problem. Overweight or obesity seems almost inevitable in adulthood, the proportion of overweight children has tripled from 5 percent to 15 percent over the past 30 years and there is increasing evidence that environmental factors may influence the development of obesity."

"Because obesity seems to be a societal problem, a public health approach should complement a clinical high-risk approach. Interventions for obesity prevention and reduction are needed in settings where people live, work, and play (including communities, work sites, and schools) as well as in clinical practice. Drug treatments for obesity should be considered within this broader context and their current role should be limited pending further evidence," they conclude.