The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men

Abstract

Tesofensine (TE) is a new drug producing twice the weight loss in obese individuals as seen with currently marketed drugs. It inhibits the presynaptic reuptake of the neurotransmitters noradrenaline, dopamine and serotonin, and is thought to enhance the neurotransmission of all three monoamines. The mechanisms by which it produces weight loss in humans are unresolved. The aim of this study is to investigate the mechanism(s) behind weight reduction by measuring energy expenditure and appetite sensations in overweight and obese individuals. Thirty-two healthy, overweight or moderately obese men were treated with 2.0 mg TE daily for 7 days followed by an additional 7 days with 1.0 mg TE daily or corresponding placebo (PL) in a randomized, controlled trial. They were instructed to maintain habitual food intake and physical activity throughout. Twenty-four-hour energy expenditure (24-h EE), fat oxidation and spontaneous physical activity were measured in a respiration chamber before and after treatment. Body composition was assessed by dual-energy X-ray absorption and appetite was evaluated by visual analogue scales in conjunction with a standardized dinner. Despite efforts to keep body weight and composition constant, TE induced a 1.8 kg weight loss above PL after 2 weeks' treatment (P<0.0001). TE also induced higher ratings of satiety and fullness and concomitantly lower prospective food intake than placebo. No significant effect of TE on total 24-h EE could be demonstrated compared with PL, but higher energy expenditure was observed during the night period (4.6%; P<0.05) when adjusted for changes in body composition. Furthermore, TE increased 24-h fat oxidation as compared with PL (18 g; P<0.001). TE has a pronounced effect on appetite sensations and a slight effect on energy expenditure at night-both effects can contribute to the strong weight-reducing effect of TE.