Sibutramine is a combined serotonin(5-HT) and noradrenaline (NA)re-uptake inhibitor. Sibutramine works predominantly through its two pharmacologically active metabolites (i.e. primary and secondary amines) which induce marked weight loss by affecting both food intake and energy expenditure. It is able to enhance the physiological process of satiety, and to stimulate thermogenesis, increasing the efferent sympathetic activity to thermogenically active brown fat. There is a dose-related reduction in body weight in clinical trials with sibutramine, with weight loss up to 11% below baseline, which can last up to 18 months with continued treatment. When weight loss is induced with a very low calorie diet (VLCDL), patients randomized to the sibutramine treatment continued to lose weight over a 1 year period, reaching 15% below baseline, whereas the placebo-treated patients regained some weight. Sibutramine improves metabolic fitness, by decreasing the biochemical risk factors associated with obesity, such as plasma triglycerides, total cholesterol and low density lipoprotein (LDL) cholesterol, glucose and insulin, and increasing HDL-cholesterol. In controlled studies, 84% of sibutramine-treated patients reported side effects, most commonly including dry mouth, constipation and insomnia, compared with 71% of patients receiving placebo. A small increase in heart rate and blood pressure also occurs and persists for as long as treatment is continued, which, therefore, requires monitoring. Nevertheless, successful treatment of moderately hypertensive obese patients with sibutramine has been demonstrated without undue blood pressure problems and even a mean lowering of blood pressure associated with weight loss. Finally, sibutramine does not have the potential for abuse that is characteristic of amphetamine and it is indistinguishable from placebo in abuse potential studies.