title: The effect of tesofensine on appetite sensations.
abstract: Tesofensine (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.
authors: Division of Kinesiology, Department of Preventive and Social Medicine, Faculty of Medicine, Laval University, Quebec City, Quebec, Canada.
authors: Jo-Anne
authors: JA
authors: Gilbert
authors: Christoph
authors: C
authors: Gasteyger
authors: Anne
authors: A
authors: Raben
authors: Dieter H
authors: DH
authors: Meier
authors: Arne
authors: A
authors: Astrup
authors: Anders
authors: A
authors: Sjödin
mesh_terms: D000328:Adult; D019440:Anti-Obesity Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001069:Appetite Regulation / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology* / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D009765:Obesity / Q000188:drug therapy*; D012527:Satiation / Q000187:drug effects*; D013997:Time Factors; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D019440:Anti-Obesity Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; C518479:Tesofensine