Managing Cardiometabolic Risk

Sibutramine

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Figure 2: Effect of a six-month treatment with sibutramine on body weight

Figure 2: Effect of a six-month treatment with sibutramine on body weight

Mechanism of action
Sibutramine was approved in the USA in 1997 and in the European Union in 1999. Originally developed as an antidepressant, sibutramine is a centrally acting, highly selective inhibitor for the reuptake at nerve endings of norepinephrine, serotonin, and, to a lesser degree, dopamine. It is a so-called “selective” serotonin norepinephrine reuptake inhibitor. This action increases satiety, thereby reducing food intake (26). In animals, sibutramine also stimulates thermogenesis, but data is conflicting in human beings. If sibutramine increases energy expenditure in humans, it is in the order of 100 kcal/day (27).

Sibutramine undergoes extensive hepatic first-pass metabolism to active primary (M1) and secondary (M2) amine metabolites, which are more potent than the parent compound (26). Most of the drug and its active metabolites are excreted by the kidney.

Efficacy
Sibutramine has been evaluated extensively in several multicentre trials. In a six-month dose-ranging study of 1,047 patients, 67% treated with sibutramine achieved a >5% weight loss from baseline, and 35% lost 10% or more. There was a clear dose–response effect, and patients regained weight when the drug was stopped, indicating that the drug remained effective while used (Figure 2). A number of other studies have reported that sibutramine can reduce weight by 3 to 6 kg more than placebo over a one- to two-year treatment period and that this effect is reproducible (5, 7, 28).

Reference

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5. Bray GA and Greenway FL. Pharmacological treatment of the overweight patient. Pharmacol Rev 2007; 59: 151-84.

7. Bray GA and Ryan DH. Drug treatment of the overweight patient. Gastroenterology 2007; 132: 2239-52.

26. McNeely W and Goa KL. Sibutramine. A review of its contribution to the management of obesity. Drugs 1998; 56: 1093-124.

27. Astrup A, Hansen DL, Lundsgaard C, et al. Sibutramine and energy balance. Int J Obes Relat Metab Disord 1998; 22 Suppl 1: S30-5; discussion S6-7, S42.

28. Padwal RS and Majumdar SR. Drug treatments for obesity: orlistat, sibutramine, and rimonabant. Lancet 2007; 369: 71-7.

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