Long-term weight loss with sibutramine - Weight Loss - Brief Article

Nutrition Research Newsletter, Dec, 2001

Obesity has reached endemic proportions and the widespread lack of clinical success calls for effective treatment of this chronic disorder. The reluctance of the medical community to treat obesity is fortunately no longer justified because short-term weight reduction achieved by interventions such as dieting, exercise, and behavior modification programs, can lead to long-term weight loss through the use of effective medicines. These drugs are designed to be used as an adjunct to non-medical therapy.

Sibutramine hydrochloride enhances satiety, primarily by blocking the reuptake of the two neurotransmitters: noradrenaline and serotonin. So fan approximately 8000 patients have taken sibutramine in clinical trials. Its effectiveness in reducing weight and achieving weight maintenance already has been shown in several randomized, double-blind studies. The aim of the current randomized study was to show equivalent weight reduction in an obese population using two therapeutic approaches: a continuous and intermittent therapy with sibutramine and the superiority of both therapies over placebo.

This 48-week multicenter study had a double-blind, placebo-controlled, randomized parallel-group design. Obese men and women (n=1001) between 18 and 65 years and with at least one unsuccessful attempt to lose weight by dietary measures in the past were recruited from 108 private practices and three hospital outpatient departments in Germany. The total treatment period for each patient was 48 weeks, comprising a run-in open-label period of four weeks and a double-blind treatment period of 44 weeks. During the run-in period, each patient was treated with 15 mg of sibutramine daily, administered orally, once daily. Patients with a weight loss of at least 2 percent and/or 2 kg or more (responders) during this period were randomized to one of the three treatment groups - continuous or intermittent therapy or placebo.

All patients took one capsule daily for the subsequent 44 weeks. Patients in continuous therapy received 15 mg of sibutramine throughout the entire study period, and those in intermittent therapy received 15 mg of sibutramine during weeks 1 through 12, 19 through 30, and 37 through 48 and then received placebo during the other weeks. The intermittent pattern was developed based on the observation that while patients are undergoing long-term treatment, the weight reduction slows down after the first three months. Assessments were made at each of the ten visits. In all, 214 patients (21.4%) did not complete the study. The proportions of withdrawals from active treatments were similar. The proportions withdrawing from placebo were significantly higher than from active treatments.

In the initial 4-week run-in phase in which all patients received 15 mg of sibutramine, weight loss was similar in the three treatment groups: patients lost a mean 4.1 kg, 4.5 kg, and 4.0 kg of body weight with subsequent treatment with continuous, intermittent, and placebo, respectively. During the 44-week randomized treatment period, mean weight loss for the ITT population was 3.8 kg for patients receiving continuous therapy and 3.3 kg for patients receiving intermittent therapy, and a mean weight gain of 0.2 kg for patients receiving placebo. In all three groups, women tended to lose more weight than men. Although there was greater weight loss in the continuous than in the intermittent study group, this difference was not significant. Overall weight loss during the 48-week period was 7.9 kg and 7.8 kg in the continuous and intermittent groups, respectively, but was 3.8 kg in the sibutramine run-in placebo group. Waist circumference reduction, triglyceride levels, and high-density lipoprotein cholesterol concentrations were also positively influenced by sibutramine treatment. Overall, adverse effects occurred at similar frequencies across all treatment groups, but the proportions was lowest in the group receiving intermittent therapy.

This randomized study showed that patients receiving continuous and intermittent therapy with sibutramine lost significantly more weight than patients receiving placebo after an initial 4-week run-in period with sibutramine. As even a moderate weight loss of 5 percent provides unquestionable benefits for obese patients, the number of patients achieving such a weight loss reflects the possible advantage of a treatment with sibutramine: more than 60 percent of the patients in the two active treatment groups lost 5 percent or more of their weight, compared with only 35 percent in the placebo group. Regarding effectiveness, continuous and intermittent sibutramine therapies are equivalent, and the safety profiles for both treatments are comparable.

A Wirth, J Krause, Long-term Weight Loss with Sibutramine. JAMA 286(11): 1331-1339 (September 2001) [Correspondence: Alfred Wirth, MD, Teutoburger-Wald-Klinik, Teutoburger-Wald-Strasse 33, Bad Rothenfelde, 49214 Germany: E-mail: wirthbr@t-online.de]