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

Abstract

Background:

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.

Objective:

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.

Design:

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.

Results:

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).

Conclusion:

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.

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Acknowledgements

We thank John Lind (technician) and Nathalie Bendsen (PhD student) for their help in collecting the data. The study was financed by NeuroSearch AS, Denmark.

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Correspondence to A Sjödin.

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Competing interests

AA and JDM receive an honorarium as a consultant and AA is a member of the Tesofensine Advisory Board for NeuroSearch A/S. AR and DM are employees of NeuroSearch A/S and own shares in the company. J-KSJ works as a consultant for NeuroSearch A/S. CG is presently employed by Merck Serono, Switzerland, while AS and ALHN have no conflict of interest.

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Sjödin, A., Gasteyger, C., Nielsen, AL. et al. The effect of the triple monoamine reuptake inhibitor tesofensine on energy metabolism and appetite in overweight and moderately obese men. Int J Obes 34, 1634–1643 (2010). https://doi.org/10.1038/ijo.2010.87

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