Thermogenic effects of sibutramine in humans

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Abstract
Sibutramine is an effective compound for the treatment of obesity, acting both on serotonergic and noradrenergic pathways. Animal studies have shown that sibutramine exerts its effect by enhancing satiety as well as by increasing thermogenesis. We tried to compare the acute thermogenic effect of a single 30-mg dose of sibutramine with placebo on basal energy expenditure (EE) and diet-induced thermogenesis. The study was randomized, double-blind, and placebo controlled. Eleven healthy, normal-weight men underwent 4 distinct treatment regimens separated by washout periods of 6-10 d. EE was measured by indirect calorimetry before and for 5.5 h after sibutramine or placebo administration with or without a 2.1-MJ breakfast. Visual analogue scales for assessment of appetite were completed hourly. Sibutramine caused a significant increase in EE above that for placebo (over 5.5 h) during both the fed (34%, 0.15 kJ/min) and fasted (183%, 0.20 kJ/min) states (P < 0.02) as well as during the last 3.5 h of this 5.5-h period and in the fed (87%, 0.26 kJ/min) and fasted (152%, 0.22 kJ/min) states, respectively (P < 0.01). The sibutramine-induced increase in EE was accompanied by an increase in plasma epinephrine (P < 0.01), heart rate (P < 0.001), blood pressure (P < 0.05), and plasma glucose (P < 0.02). About 25% of the increased heart rate with sibutramine could be explained by increased thermogenesis. Sibutramine increased satiety more than did placebo (5-h area under the curve, P < 0.05). Sibutramine caused a significant increase in both EE and satiety, which may both contribute to its weight-reducing properties.