Context: Treatment of obesity requires long-term therapy, which can be hampered by difficulties in achieving patient compliance. The effectiveness of sibutramine hydrochloride in treating obesity has been shown in randomized controlled trials.
Objective: To compare the effectiveness of 2 distinct sibutramine regimens with each other and with placebo for weight reduction among obese persons.
Design: Randomized, double-blind, parallel-group placebo-controlled trial from 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)) entered the 4-week open-label run-in period with 15 mg/d of sibutramine, 1001 of whom had weight loss of at least 2% or 2 kg were randomized into the 44-week randomized treatment period.
Interventions: Patients were randomly assigned to receive 15 mg/d of sibutramine continuously throughout weeks 1-48 (n = 405); 15 mg/d of sibutramine intermittently during weeks 1-12, 19-30, and 37-48, with placebo during all other weeks (n = 395); or placebo for weeks 5-48 (n = 201).
Main outcome measure: Weight loss during the randomized treatment period, compared 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 continuous 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 kg) in patients receiving placebo. Therapeutic equivalence of the 2 active treatments could be shown. Although there was a greater weight loss in the continuous than in the intermittent group, this difference was nonsignificant (P =.28) and the 95% CIs were within the predefined range of therapeutic equivalence-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 sibutramine run-in placebo group. Waist circumference reduction, triglyceride levels, and high-density lipoprotein cholesterol concentrations were also positively influenced by sibutramine treatment. Systolic and diastolic blood pressures were stable across all 3 groups. Overall, adverse events occurred at similar frequencies across all treatment groups, but the proportion was lowest in the group receiving intermittent therapy.
Conclusions: Sibutramine, administered for 48 weeks to a typically obese population, 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.