Weight Loss Produced by Tesofensine in Patients With Parkinson's or Alzheimer's Disease

• Published in: Obesity (Silver Spring, Md.) Vol. 16; no. 6; pp. 1363 - 1369
• Main Authors: Astrup, Arne, Meier, Dieter H, Mikkelsen, Birgit O, Villumsen, John S, Larsen, Thomas M
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.2008
• Subjects: Adult; Aged; Aged, 80 and over; Alzheimer disease; Alzheimer Disease - drug therapy; Alzheimer Disease - physiopathology; Alzheimer's disease; Biogenic Monoamines - antagonists & inhibitors; Blood pressure; Blood Pressure - drug effects; Blood Pressure - physiology; body mass index; Bridged Bicyclo Compounds, Heterocyclic - adverse effects; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Bridged Bicyclo Compounds, Heterocyclic - therapeutic use; Cardiovascular disease; Coronary vessels; Diabetes; Dopamine; Dose-Response Relationship, Drug; Double-Blind Method; drug therapy; Eating disorders; Female; Heart rate; Heart Rate - drug effects; Heart Rate - physiology; Humans; inhibitors; Male; meta-analysis; Metabolic syndrome; Middle Aged; Mortality; Multicenter Studies as Topic; norepinephrine; Obesity; Obesity - drug therapy; Obesity - physiopathology; Parkinson disease; Parkinson Disease - drug therapy; Parkinson Disease - physiopathology; Parkinson's disease; patients; Randomized Controlled Trials as Topic; Serotonin; Serotonin Uptake Inhibitors - adverse effects; Serotonin Uptake Inhibitors - pharmacology; Serotonin Uptake Inhibitors - therapeutic use; Vein & artery diseases; Weight control; weight loss; Weight Loss - drug effects; Weight Loss - physiology; Denmark
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1038/oby.2008.56

Objective: Tesofensine (TE) is a norepinephrine, dopamine, and serotonin reuptake inhibitor. We conducted a meta‐analysis of TE's effect on body weight in trials investigating its potential for treatment of Parkinson's or Alzheimer's disease. Methods and Procedures: Four randomized, double‐blind, multicenter trials compared TE (n = 740) and placebo (n = 228), two in each disease. Patients received oral TE or placebo once daily for 14 weeks without any weight loss program. Results were adjusted for baseline values, age, and study. Results: In the placebo group, 14% were obese and 21% were in the TE group. In the total cohort, weight change after 14 weeks was +0.5, −0.5, −0.9, −1.8, −2.8% in the placebo, 0.125, 0.25, 0.5 and 1.0 mg in the TE groups, respectively (P = 0.015 for dose effect). In the obese subgroup, weight changes were −0.2, −1.7, −1.6, −1.5, −3.7%, and 2.1, 8.2, 14.1, 20.9, 32.1% of the obese patients achieved ≥5% weight loss (P < 0.001 for 0.25, 0.5, and 1.0 mg vs. placebo for both end points). Changes in heart rate were −0.4, 2.1, 4.2, 6.0, and 6.8 bpm after 14 weeks (TE vs. placebo: P < 0.001 from 0.25 mg), but no effect on blood pressure was observed. Discussion: TE produced a placebo‐subtracted weight loss of ∼4% for >14 weeks without any diet and lifestyle therapy, which is similar to that of sibutramine, but with no effect on blood pressure. On the basis of these results, TE is now being developed for obesity management.