The effect of sibutramine on resting energy expenditure and adrenaline-induced thermogenesis in obese females

Abstract

BACKGROUND: Sibutramine, an inhibitor of serotonin and noradrenaline uptake, reduces appetite to cause weight loss. This study tested the hypothesis that an increase in energy expenditure also contributes to this weight loss. In addition, the effects of sibutramine on adrenaline induced changes in heart rate and cardiac output were determined METHODS: Nineteen obese females randomly received either sibutramine 15 mg daily or placebo for 12 weeks along with dietary advice. Resting energy expenditure (REE) was measured and then energy expenditure was measured during a 30 min infusion of adrenaline (25 ngaminakg IBW). Cardiac output and heart rate, measured by Duplex Colour Doppler ultrasonography, were similarly measured in the basal state and post adrenaline. All measurements were recorded at baseline and then after 12 weeks. RESULTS: Ten patients who received sibutramine reduced their weight by 8.1 AE 3.8% while 9 placebo treated subjects reduced their weight by 5.1 AE 4.4%, P 0.13. In absolute terms, REE decreased in placebo subjects from 1500 AE 201 kcala24 h to 1357 AE 231 kcala24 h (9.4 AE 9.9%) and in sibutramine subjects from 1540 AE 184 kcala24 h to 1444 AE 128 kcala24 h (5.3 AE 12.0%), P 0.77. The increased weight loss in the sibutramine group was associated with an increase in the FFM adjusted REE (2.2 AE 16.1%) unlike the expected decrease (5.8 AE 9.5%) in the placebo group (P 0.11). There was some suggestion (P 0.09) that the usual positive correlation between loss of weight and decline in REE was lost in the sibutramine group (r 7 0.30) compared with placebo (r 0.35). There was a negative correlation between loss of FFM and decline in REEakg FFM and (P 0.029) which was not evident in placebo (P 0.83). Adrenaline induced energy expenditure was similar in the two groups at the end of the 12 week period and there were no signi®cant cardiovascular changes between the two groups. CONCLUSIONS: Sibutramine limits the decline in REE associated with weight loss, equivalent to about 100 kcalad. This could allow greater numbers of people to maintain a greater degree of weight loss.

Efficacy and safety of sibutramine for weight loss in obese patients with hypertension well controlled by β-adrenergic blocking agents: a placebo-controlled, double-blind, randomised trial

“…8,14 Additionally, sibutramine has been shown to increase energy utilisation. 19,20 The increased energy utilisation activity of sibutramine may be indirectly generated by central stimulation of efferent sympathetic output to the ␤ 3 -adrenoceptors in brown adipose tissue. 20,21 Increase in energy expenditure with sibutramine treatment has been reported in two studies 19,20 Journal of Human Hypertension although not in one other.…”

“…19,20 The increased energy utilisation activity of sibutramine may be indirectly generated by central stimulation of efferent sympathetic output to the ␤ 3 -adrenoceptors in brown adipose tissue. 20,21 Increase in energy expenditure with sibutramine treatment has been reported in two studies 19,20 Journal of Human Hypertension although not in one other. 22 This possible dual mechanism of action may enhance the efficacy of sibutramine by diminishing the decrease in metabolic rate normally encountered upon initial weight loss.…”

Influence of Sibutramine on blood pressure: evidence from placebo-controlled trials

“…[5][6][7] Sibutramine mediates increased satiety, although a mild increase in energy expenditure may also contribute to weight loss. 8 Norepinephrine uptake inhibition with sibutramine in peripheral tissues could exacerbate arterial hypertension through an increase in synaptic norepinephrine concentrations. Indeed, when applied locally to peripheral tissues, norepinephrine transporter blockade increases norepinephrine overflow.…”

Efficacy and safety of sibutramine in 2225 subjects with cardiovascular risk factors: short-term, open-label, observational study

“…11,12 Controlled clinical studies have shown that sibutramine produces dose-related weight reduction in obese subjects, as early as 2 weeks after initiation of treatment. 13 However, the norepinephrine activation induced by sibutramine administration could lead to an increase in arterial blood pressure and elevation of heart rate in some patients.…”