EFFICACY AND TOLERABILITY OF SIBUTRAMINE IN OBESE PATIENTS - A DOSE-RANGING STUDY

OBJECTIVES: To assess the weight-reducing effects and tolerability of 5 mg, 10 mg and 15 mg daily doses of sibutramine, a novel serotonin an d noradrenaline reuptake inhibitor (SNRI). DESIGN: Multicentre, double -blind, and placebo-controlled study. After a one week run-in period, patients were randomized to receive placebo or sibutramine over a 12-w eek period. Advice on diet and behaviour modification was provided. On e follow-up was conducted four weeks after cessation of treatment. SUB JECTS: 235 obese outpatients, aged 18-55 y with a body mass index (BMI ) within the range 27-40 kg/m(2). MEASUREMENTS: Weight, height, waist and hip circumference, and medical history, assessment of hunger, sati ety, appetite and craving for sweet, savoury and carbohydrate foods, a nd also for carbohydrate snacking, standard laboratory assessments, bl ood pressure, heart rate and EGG. RESULTS: The group mean (+/- s.e.m.) weight loss at end-point was 1.4 +/- 0.5 kg for placebo (n = 59), 2.4 +/- 0.5 kg for 5 mg sibutramine (n = 56), 5.1 +/- 0.5 kg for 10 mg si butramine (n = 59) and 4.9 +/- 0.5 kg (n = 62) for 15 mg sibutramine. The difference observed between the placebo and the 10 mg and 15 mg gr oups was statistically significant from week 2 onwards (P < 0.01), but there was no significant difference between these sibutramine groups. The percentage of patients losing >5% of initial bodyweight was signi ficantly greater for 15 mg sibutramine (55%) and 10 mg sibutramine (49 %) than for treatment with placebo (19%), (P < 0.001). During the doub le-blind period, 41 patients (17%) withdrew prematurely and 168 patien ts (71%) reported 453 adverse events. The incidence and type of advers e event and the rates of withdrawal, were not significantly different in the four groups. No significant differences between the groups were observed, in respect of changes in systolic and diastolic blood press ure, but a significant increase in heart rate (about 4 beats/min) was noted for patients who received 10 mg or 15 mg sibutramine, compared w ith the placebo (P < 0.001). CONCLUSION: These data demonstrate dose-r elated weight loss with sibutramine treatment for up to 12 weeks in ob ese patients. Doses of 10 mg and 15 mg once daily were shown to be sim ilarly effective, well tolerated and significantly more effective than the placebo.