Q&A
Does long-term use of sibutramine (Meridia) result in continued weight loss in short-term responders?
- BACKGROUND: Obesity, defined as a body mass index (BMI) equal to or greater than 30 kg/m2, is a common chronic disorder with a prevalence of 22.3% in American adults.1 There is significant interest in pharmacologic interventions for this disorder because of the difficulty achieving and maintaining significant weight loss solely with lifestyle chan ges. Two drugs, sibutramine and orlistat (Xenical), have recently been approved by the Food and Drug Administration for long-term (greater than 12 weeks) management of obesity.
- POPULATION STUDIED: The researchers enrolled 1102 obese (BMI = 30-40 kg/m2) adults from 111 privat e practices or outpatient clinics in Germany. Almost all subjects were white, and 75% were women aged between 18 and 65 years. After randomization, treatment groups were well matched demographically and had similar weights, BMI (mean = 34.8 kg/m2), and waist circumference. Patients were excluded if they were pregnant or had serious cardiovascular or metabolic diseases, history of drug or alcohol abuse, depression, or treatment with antidepressants, β-blockers, or any drug influencing body weight.
- STUDY DESIGN AND VALI DITY: This was a randomized (allocation assignment concealed) double-blind trial funded by the manufacturer of sibutramine. All patients were treated unblinded with 15 mg per day of sibutramine for 4 weeks. Patients with at least a 2% or 2 kg weight loss (responders) were then randomized to 1 of 3 treatment groups: 15 mg per day of sibutramine continuously during weeks 5 to 48; 15 mg per day of sibutramine intermittently during weeks 5 to 12, 19 to 30, and 37 to 48 and a placebo on all other days; or placebo once daily for weeks 5 to 48.
- OUTCOMES MEASURED: The primary outcome was weight loss during the 44-week randomized period. Secondary outcomes included waist circumference, heart rate, blood pressure, cholesterol levels, and side effects.
- RESULTS: The average weight loss for the 1001 patients completing the 4-week nonblinded run-in period was 4.2 kg and was similar for patients going into each of the 3 treatment groups. Using intention-to-treat analysis, sustained mean weight loss during the 44-week randomized treatment period was 3.8 kg (4.0%) with continuous sibutramine therapy (95% confidence interval [CI], -4.42 to -3.20 kg) and 3.3 kg (3.5%) with intermittent therapy (95% CI, -3.96 to -2.66 kg). Mean weight gain in the placebo group was 0.2 kg (95% CI, -0.60 to 0.94 kg). Minimal decreases in low-density lipoprotein cholesterol (-5 mg/dL) occurred in both sibutramine treatment groups, but blood pressure was not affected. During the 4-week run-in period where everyone received sibutramine, 14% of the patients experienced drug-related adverse effects. During the 44-week double -blinded period, the proportion of withdrawals because of adverse events was similar across the 3 study groups. Twenty-one percent of the original subjects did not complete the entire 48-week study.