Weight Loss in Response to Sibutramine (MERIDIA) is Influenced by the Inherited Genes

Background:. Genetic variations are potentially key to inter-individual differences in responses to treatment with the appetite suppressant sibutramine. Overall Aims: To evaluate influence of genetic variation in candidate adrenergic and serotonergic control mechanisms on weight loss and gastric emptying response to sibutramine in obesity. Methods: 180 overweight or obese (respectively BMI of 25-29.9 or 30 kg/m2) people treated with sibutramine (10 or 15 mg/day) or placebo for 12 wks. We shall collect DNA from venous blood sample at study entry, and use SERT-P genotype at baseline to stratify patients according to LL vs LS/SS genotype in both obese and overweight groups. The primary outcome measurement will be the association of clinical response (weight loss) and the influence of SERT-P and 2-MSP variation. A secondary outcome for descriptive purposes is the gastric emptying response to sibutramine treatment. Gastric emptying of solids will be measured using stable isotope method. Anticipated Results: SERT-P genotype is significantly associated with the magnitude of weight loss in obese and overweight individuals. Significance: Our study will provide the first evidence of the pharmacogenomic effects of sibutramine on weight loss in obesity and appraise the association of weight loss with change in gastric emptying.