A Review of the Metabolic Effects of Sibutramine

T. D. Filippatos; D. N. Kiortsis; E. N. Liberopoulos; D. P. Mikhailidis; M. S. Elisaf

Disclosures

Curr Med Res Opin. 2005;21(3):457-468. 

In This Article

Weight Reduction and Maintaining Weight Loss

In a 6-month study[37] (1047 patients), sibutramine (1 mg/ day-30 mg/day) resulted in significant dose-related weight loss (sibutramine 1 mg, 2.7%; 5 mg, 3.9%; 10 mg, 6.1%; 30 mg, 9.4%; placebo, 1.2%; p < 0.05 sibutramine 5 mg/day-30 mg/day vs. placebo). In another 44- week study,[38] the efficacy of an intermittent regimen (sibutramine 15 mg/day for week 1-week 12, week 19-week 30, week 37-week 48 and placebo during all other weeks) was compared with continuous therapy with sibutramine 15 mg/day. No significant difference in weight reduction was observed between the two regimens. The Sibutramine Trial of Obesity Reduction and Maintenance (STORM)[23] investigated the use of sibutramine for maintaining weight loss after an initial 6 months of treatment with sibutramine 10 mg/day in conjunction with a low-calorie diet (600 kcal/day deficit) in 605 patients [body mass index (BMI) 30 kg/m2-45 kg/m2]. In the weight-maintenance phase, 467 (77%) patients who lost at least 5% of body weight were randomised to receive sibutramine 10 mg/day-20 mg/ day ( n = 352) or placebo ( n = 115) for 18 months. Among completers (the dropout rate was 42% and 50%, respectively), 43% of the sibutramine group and 16% of the placebo group maintained at least 80% of their weight loss after 2 years ( p < 0.001). In this study, continued use of sibutramine helped to maintain weight loss for up to 2 years after the start of therapy. Moreover, pre-treatment body weight seems to be an important independent predictor of weight loss at 6 months and weight maintenance at 24 months in the STORM trial.[39] In this trial, a later analysis showed that a higher leisure-time physical activity index was also associated with maintaining weight loss.[40] Another study[41] showed that psychobehavioural and nutritional characteristics could be used as predictors of weight loss in response to a comprehensive weight management program including treatment with sibutramine.

Sibutramine treatment not only results in weight loss, but also in visceral fat reduction, which is associated with insulin resistance and the metabolic syndrome.[42] Specifically, a meta-analysis[43] of 4 placebo-controlled, doubleblind studies found that sibutramine significantly reduces waist circumference ( p < 0.001) and the waist-to-hip ratio ( p < 0.02). Van Gaal et al .[43] examined the changes in fat distribution using computerised tomography (CT) scans as part of the STORM study. After sibutramine treatment (10 mg/day) for 6 months, decreases in total abdominal fat (18%), total subcutaneous fat (17%) and total visceral fat (22%) were observed and there was a significant increase in the subcutaneous-to-visceral fat ratio ( p < 0.05). These changes in fat levels and distribution were associated with improvements in related risk factors, such as fasting blood glucose, insulin levels and BP. Furthermore, Kamel et al .[44] estimated the changes in intra-abdominal adipose tissue measured by magnetic resonance imaging in patients receiving 10 mg/ day sibutramine and a low-calorie diet for 6 months and concluded that the percentage of changes in intraabdominal adipose tissue was greater than that in subcutaneous adipose tissue ( p < 0.01). In this study, changes in intra-abdominal adipose tissue were significantly correlated with changes in weight and BMI.

The Long-Term Outcomes of Sibutramine Effectiveness on Weight (LOSE Weight) study[45] was a prospective randomised controlled trial that enrolled 588 obese patients starting a weight management program. Patients were randomly assigned to participate in the program alone or to also receive sibutramine for 12 months. The mean weight loss at 6 months was 6.8 kg in the drug group vs. 3.1 kg in the control group ( p < 0.001). Weight loss was maintained at 12 months and significant reductions in BMI, body fat and waist circumference occurred in the sibutramine group.

There are limited data regarding the efficacy of sibutramine in non-white populations. A study[22] that included 36% black obese patients with controlled hypertension found similar efficacy of sibutramine in that subgroup. Berkowitz et al .[46] examined whether additional weight loss in obese adolescents is obtained when sibutramine is added to a family-based, behavioural weight control program. They concluded that adding sibutramine to such a program induced significantly more weight loss than did placebo. However, until more extensive safety and efficacy data are available, sibutramine should only be used in ethically approved trials in adolescents and children.

In another study,[47] sibutramine administration in obese hypopituitary patients ( n = 14) resulted in at least 5% weight loss in almost all patients, while 60% of these lost > 10% weight within 11 months of treatment. Two recent studies assessed the efficacy of combination therapy with sibutramine and orlistat.[48,49] The combination and sibutramine monotherapy were both more effective than orlistat alone. However, no significant difference was noticed between combination drug therapy and sibutramine treatment groups. In another study,[50] treatment with a 'higher' dose of sibutramine (10 mg twice a day) was more effective ( p < 0.0001) than 'conventional doses' of orlistat (120 mg three times a day) or metformin (850 mg twice a day) therapy in terms of weight reduction in obese women.

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