PMID-18950853 – Tesofensine Phase 2 Obesity Trial

PMID-18950853 – Tesofensine Phase 2 Obesity Trial

Astrup A, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372(9653):1906-1913.

Quick Reference

Property Value
PMID 18950853
DOI 10.1016/S0140-6736(08)61525-1
Year 2008
Journal The Lancet
Study Type RCT
Evidence Level II
Sample 203 obese patients (BMI 30-40 kg/m2)
Peptide(s) Studied Tesofensine

Key Findings

  • Mean weight loss with diet + placebo was 2.0% over 24 weeks
  • Tesofensine 0.25 mg produced 4.5% greater weight loss vs placebo (p<0.0001)
  • Tesofensine 0.5 mg produced 9.2% greater weight loss vs placebo (p<0.0001)
  • Tesofensine 1.0 mg produced 10.6% greater weight loss vs placebo (p<0.0001)
  • Quality of life improvements correlated with weight loss magnitude
  • Body composition analysis showed preferential fat mass loss

Study Design

Phase 2, multicentre, randomised, double-blind, placebo-controlled trial conducted at 5 Danish obesity management centres. 203 patients randomized to tesofensine 0.25 mg, 0.5 mg, 1.0 mg, or placebo for 24 weeks. All groups received a controlled energy-deficit diet. Primary endpoint: percent body weight change.

Limitations

  • 24-week duration; long-term efficacy/safety unknown
  • Moderate sample size (n=203)
  • Single-country study (Denmark only)
  • No Phase 3 confirmatory trial conducted subsequently
  • Heart rate increased 7.4 bpm in 0.5 mg group (p=0.0001)

Clinical Relevance

This is the pivotal Phase 2 trial demonstrating tesofensine's potential as an anti-obesity agent. The 0.5 mg dose appeared to have the best risk-benefit profile, producing ~9% weight loss with manageable side effects. The weight loss magnitude exceeded that of all FDA-approved anti-obesity drugs at the time. However, the lack of Phase 3 completion limits clinical translation.

Related

#research #RCT #tesofensine #evidence-level-II