Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial

被引:139
作者
Astrup, Arne [1 ]
Madsbad, Sten [2 ]
Breum, Leif [3 ]
Jensen, Thomas J. [4 ]
Kroustrup, Jens Peter [5 ]
Larsen, Thomas Meinert [1 ]
机构
[1] Univ Copenhagen, Dept Human Nutr, Fac Life Sci, DK-1958 Frederiksberg, Denmark
[2] Univ Copenhagen, Dept Endocrinol, DK-1958 Frederiksberg, Denmark
[3] Koge Hosp, Dept Med, Koge, Denmark
[4] Cyncron Clin Res Unit, Copenhagen, Denmark
[5] Aalborg Hosp, Dept Endocrinol, Aalborg, Denmark
关键词
D O I
10.1016/S0140-6736(08)61525-1
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Weight-loss drugs produce an additional mean weight loss of only 3-5 kg above that of diet arid placebo over 6 months, and more effective pharmacotherapy of obesity is needed. We assessed the efficacy and safety of tesofensine-an inhibitor of the presynaptic uptake of noradrenaline, dopamine, and serotonin-in patients with obesity. Methods We undertook a phase II, randomised, double-blind, placebo-co n trolled trial in five Danish obesity management centres. After a 2 week run-in phase, 203 obese patients (body-mass index 30-<= 40 kg/m(2)) were prescribed an energy restricted diet and randomly assigned with a list of randomisation numbers to treatment with tesofensine 0 . 25 mg (n=52), 0.5 mg (n=50), or 1 . 0 mg (n=49), or placebo (n=52) once daily for 24 weeks. The primary outcome was percentage change in bodyweight. Analysis was by modified intention to treat (all randomised patients with measurement after at least one dose of study drug or placebo). The study is registered with ClinicalTrials.gov, number NCT00394667. Findings 161 (79%) participants completed the study. After 24 weeks, the mean weight loss produced by diet and placebo was 2.0% (SE 0. 60). Tesofensine 0 . 25 mg, 0. 5 ing, and 1. 0 mg and diet induced a mean weight loss of 4.5% (0 . 87), 9.2% (0.91), and 10 . 6% (0-84), respectively, greater than diet and placebo (p<0. 0001). The most common adverse events caused by tesofensine were dry mouth, nausea, constipation, hard stools, diarrhoea, and insomnia. After 24 weeks, tesofensine 0 . 25 mg and 0 . 5 mg showed no significant increases in systolic or diastolic blood pressure compared with placebo, whereas heart rate was increased by 7.4 beats per min in the tesofensine 0. 5 mg group (p = 0. 0001). Interpretation Our results suggest that tesofensine 0 . 5 mg might have the potential to produce a weight loss twice that of currently approved drugs. However, these findings of efficacy and safety need confirmation in phase III trials. Funding Neurosearch A/S, Denmark.
引用
收藏
页码:1906 / 1913
页数:8
相关论文
共 22 条
[1]   Long-term mortality after gastric bypass surgery [J].
Adams, Ted D. ;
Gress, Richard E. ;
Smith, Sherman C. ;
Halverson, R. Chad ;
Simper, Steven C. ;
Rosamond, Wayne D. ;
LaMonte, Michael J. ;
Stroup, Antoinette M. ;
Hunt, Steven C. .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 357 (08) :753-761
[2]  
[Anonymous], 1998, OB PREV MAN GLOB EP
[3]  
Astrup A, 2005, LANCET, V366, P368, DOI 10.1016/S0140-6736(05)67017-1
[4]   Weight loss produced by tesofensine in patients with Parkinson's or Alzheimer's disease [J].
Astrup, Arne ;
Meier, Dieter H. ;
Mikkelsen, Birgit O. ;
Villumsen, John S. ;
Larsen, Thomas M. .
OBESITY, 2008, 16 (06) :1363-1369
[5]  
Ayyad C, 2000, Obes Rev, V1, P113, DOI 10.1046/j.1467-789x.2000.00019.x
[6]   Beneficial physiological and performance responses to a month of restricted energy intake in healthy overweight women [J].
Buffenstein, R ;
Karklin, A ;
Driver, HS .
PHYSIOLOGY & BEHAVIOR, 2000, 68 (04) :439-444
[7]   Efficacy and safety of the weight-loss drug rimonabant: a meta-analysis of randomised trials [J].
Christensen, Robin ;
Kristensen, Pernelle Kruse ;
Bartels, Else Marie ;
Blidda, Henning ;
Astrup, Arne .
LANCET, 2007, 370 (9600) :1706-1713
[8]   Reproducibility, power and validity of visual analogue scares in assessment of appetite sensations in single test meal studies [J].
Flint, A ;
Raben, A ;
Blundell, JE ;
Astrup, A .
INTERNATIONAL JOURNAL OF OBESITY, 2000, 24 (01) :38-48
[9]   Thermogenic effects of sibutramine in humans [J].
Hansen, DL ;
Toubro, S ;
Stock, MJ ;
Macdonald, IA ;
Astrup, A .
AMERICAN JOURNAL OF CLINICAL NUTRITION, 1998, 68 (06) :1180-1186
[10]   The effect of sibutramine on energy expenditure and appetite during chronic treatment without dietary restriction [J].
Hansen, DL ;
Toubro, S ;
Stock, MJ ;
Macdonald, IA ;
Astrup, A .
INTERNATIONAL JOURNAL OF OBESITY, 1999, 23 (10) :1016-1024