Four-year efficacy and safety of sibutramine for weight maintenance: a multicenter, double-blind, randomized, placebo-controlled study

Long-term maintenance of weight after weight loss is a serious challenge. This study recruited individuals who had lost >10 kg, randomized them to placebo or sibutramine and planned to follow them for 5 years at 26 sites. Eligible subjects had lost >10 kg in nonpharmacological weight loss programs (NPWLP) and maintained a weight loss of >10 kg for 6 months (mos). After baseline measurements subjects were randomized to placebo or sibutramine 15 mg/d for study duration. Randomized subjects were: placebo, 230 and sibutramine, 236. Demographics at baseline were: female 74%; Caucasian 94%; age 48 years; body weight 91 kg; and BMI 32 kg/m². Subjects had entered NPWLP 29 months prior to baseline, weighed 114 kg (BMI 43 kg/m²), lost a maximum of 30 kg in 26 weeks, and at baseline were 23 kg below weight at starting NPWLP. The study was terminated after all subjects had completed 36 mos. Data were available for adequate subjects to assess weight maintenance at 48 months. Behavioral modification classes were provided weekly for 1 yr and then monthly. Subjects attended 8 weeks of “Healthy Solutions” classes starting at 18, 30 and 42 mos. The primary efficacy measures were percentage weight changes at 36 mos. Data analyses for eligible subjects and for the last-observation-carried-forward (LOCF) were performed. Weight changes did not differ significantly (P=0.074) between groups at 36 mos with a 13.4% (se 1.2) increase for placebo (n= 148) and a 11.9% (se 1.2, n 143) increase for sibutramine. LOCF analysis indicated that weight gains were significantly lower for sibutramine treatment at 6, 12, and 24 mos but not at 36 mos. Weight gain for observed subjects plateaued after 24 mos and averaged 12.4% above baseline. The total incidence of side effects did not differ significantly between groups. In this high risk population over 4 years there were 3 deaths (2 placebo, 1 sibutramine). Thus, severely obese subjects who lost 26.3% (30.1 kg) of initial body weight in NPWLP maintained weight losses of 37.8% (11.4 kg) over the follow-up of 5-6 years after their initial weight loss. Sibutramine significantly enhanced weight maintenance for the first 24 months.