Prediction of Successful Weight Reduction Under Sibutramine Therapy Through Genotyping of the G-protein beta3 Subunit Gene (GNB3) C825T Polymorphism

Pharmacogenetics. 2003 Aug;13(8):453-9. doi: 10.1097/00008571-200308000-00003.


Background: Sibutramine, a centrally acting noradrenaline and serotonin re-uptake inhibitor, enhances satiety and is frequently used to support weight loss. However, a significant variability exists among individuals concerning the response to sibutramine.

Methods: We genotyped 111 participants of a randomized placebo-controlled clinical trial for the GNB3 C825T polymorphism and analysed associations of genotypes with treatment outcome. Patients undergoing a structured weight loss programme were treated with either placebo or 15 mg sibutramine daily for 54 weeks.

Results: In the placebo group, the non-pharmacological programme alone resulted in a significantly greater weight loss in individuals with the GNB3 TT/TC genotypes as compared to individuals with the CC genotype (-7.1 +/- 1.2 vs. -2.7 +/- 1.5 kg, P = 0.031). Administration of 15 mg sibutramine was more effective in individuals with the CC genotype than in the subjects with the TT/TC genotypes (weight loss: 7.2 +/- 2.2 vs. 4.1 +/- 2.1 kg, P = 0.0013, sibutramine vs. placebo). In the CC genotype carriers, the odds ratio (OR) for a weight loss greater than 5% (sibutramine vs. placebo) was 6.6 (95% CI 1.8-25.6; P = 0.004) and for a weight loss greater than 10% was 9.6 (95% CI 1.7-53.8; P = 0.010).

Conclusion: Genotyping for the GNB3 C825T polymorphism is highly predictive for the identification of obese individuals who will benefit from sibutramine treatment.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Appetite Depressants / therapeutic use*
  • Cyclobutanes / therapeutic use*
  • GTP-Binding Protein beta Subunits / genetics*
  • Genotype
  • Humans
  • Middle Aged
  • Obesity / drug therapy*
  • Placebos
  • Polymorphism, Genetic*


  • Appetite Depressants
  • Cyclobutanes
  • GTP-Binding Protein beta Subunits
  • Placebos
  • sibutramine