• Jo-Anne Gilbert, Christoph Gasteyger, Anne Raben, Dieter H Meier, Arne Astrup, and Anders Sjödin.
• Division of Kinesiology, Department of Preventive and Social Medicine, Faculty of Medicine, Laval University, Quebec City, Quebec, Canada.
• Obesity (Silver Spring). 2012 Mar 1; 20 (3): 553-61.

AbstractTesofensine (TE), an inhibitor of monoamine presynaptic reuptake, has produced twice the weight loss seen with currently marketed drugs. However, its long term effect on appetite in humans has not been studied. A multicentre phase II trial was divided into two parts (24 weeks each). Part 1 had a randomized, double-blind, placebo-controlled design and Part 2, an open-labeled, single-group, uncontrolled design. A drug-free period (12 ± 3 weeks) separated them. In Part 1, participants (n = 158) were assigned to 0.25, 0.5 or 1.0 mg TE, or placebo. Completers of Part 1 were invited to participate in Part 2 (n = 113), during which they all received 0.5 or 1.0 mg TE. Appetite sensations and a composite satiety score (CSS = satiety + fullness + (100 - hunger) + (100 - prospective food consumption) were assessed. In Part 1 TE induced a dose-dependent increase in CSS at week 12 that correlated with weight loss during the 24 weeks (r = 0.36, P < 0.0001). However, CSS diminished over time as weight loss progressed (e.g., for 1.0 mg; 52 ± 17 mm; 64 ± 13 mm; 55 ± 13 mm at baseline, week 12 and week 24, respectively). After drug withdrawal CSS returned to baseline values (50 ± 17 mm, in the whole sample.), despite the participants' reduced-weight state (-7.2 ± 6.7 kg, P < 0.0001). The reintroduction of TE in Part 2 increased CSS again (56 ± 17 mm at week 60), regardless of initial treatment/weight loss. We postulate that enhanced satiety is involved in early weight loss. Whether the attenuated effect on appetite seen after 24 weeks is due to a counteracting effect in the weight reduced state or whether the appetite suppressing effect of TE per se diminishes over time is, however, still unclear.

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