Long-term weight loss with sibutramine - A randomized controlled trial

Context Treatment of obesity requires long-term therapy, which can be hampe red by difficulties in achieving patient compliance. The effectiveness of s ibutramine hydrochloride in treating obesity has been shown in randomized c ontrolled trials. Objective To compare the effectiveness of 2 distinct sibutramine regimens w ith each other and with placebo for weight reduction among obese persons. Design Randomized, double-blind, parallel-group placebo-controlled trial fr om April 1997 to September 1998. Setting One hundred eight private practices and 3 outpatient departments of university hospitals in Germany. Patients A total of 1102 obese adults (body mass index, 30-40 kg/m(2)) ente red the 4-week open-label run-in period with 15 mg/d of sibutramine, 1001 o f whom had weight loss of at least 2% or 2 kg were randomized into the 44-w eek randomized treatment period. Interventions Patients were randomly assigned to receive 15 mg/d of sibutra mine continuously throughout weeks 1-48 (n=405); 15 mg/d of sibutramine int ermittently during weeks 1-12, 19-30, and 37-48, with placebo during all ot her weeks (n=395); or placebo for weeks 5-48 (n=201). Main Outcome Measure Weight loss during the randomized treatment period, co mpared among all 3 groups. Results Mean weight loss in the intention-to-treat population during the 44 -week randomized treatment period was 3.8 kg (4.0%) in patients receiving c ontinuous therapy (95% confidence interval [CI], -4.42 to -3.20 kg) and was 3.3 kg (3.5%) in patients receiving intermittent therapy (95% CI, -3.96 to -2.66 kg), vs a mean weight gain of 0.2 kg (0.2%) (95% CI, -0.60 to 0.94 k g) in patients receiving placebo. Therapeutic equivalence of the 2 active t reatments could be shown. Although there was a greater weight loss in the c ontinuous than in the intermittent group, this difference was nonsignifican t (P=:28) and the 95% Cis were within the predefined range of therapeutic e quivalence-0 +/-1.5 kg (-1.37 to 0.28 for the intent-to-treat population). 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 sib utramine run-in placebo group. Waist circumference reduction, triglyceride levels, and high-density lipoprotein cholesterol concentrations were also p ositively influenced by sibutramine treatment. Systolic and diastolic blood pressures were stable across all 3 groups. overall, adverse events occurre d at similar frequencies across all treatment groups, but the proportion wa s lowest in the group receiving intermittent therapy. Conclusions Sibutramine, administered for 48 weeks to a typically obese pop ulation, results in clinically relevant weight loss compared with placebo. Regarding effectiveness, continuous and intermittent sibutramine therapies are equivalent and the safety profiles for both treatments are comparable.