Early Thermogenic Response to Sibutramine in Obese Women

Abstract

Sibutramine was introduced as an energy balance regulator with the potential to modify both energy intake and heat generation in the management of obesity. Several studies have been done to investigate the effect of serotoninergic drugs on energy expenditure in humans. Most of the earlier studies found no effect of these agents on basal metabolic rate. Sibutramine has been shown to increase satiety in humans. In addition to reducing energy intake, sibutramine also increases energy expenditure in rodents by activating central efferent sympathetic nerves innervating brown fat, thus mimicking the non-shivering thermogenic response to cold. Our objective in the present study has been to asses the early (15 days) thermogenic effects of sibutramine in obese patients. Thirty obese women (mean age 39± 11.6 yr) were enrolled in the study. Each patient received 10 mg sibutramine daily for 15 days and restricted their diets to 500 kcal/dayless than the normal daily requirement. Inclusion criteria were age range 20-50 and Body Mass Index (BMI) 25-40 kg/m2. Exclusion criteria were systolic blood pressure greater than 140 mmHg and diastolic blood pressure greater than 80 mmHg. Thermogenic response measurements were performed by direct calorimetry prior to medication and after the 15-day treatment period. Baseline (before medication) mean thermogenic response was found to be 0.97±0.03 kcal/h/kg. It increased to 1,26±0.17 kcal/kg/h at the end of the 15-day sibutramine
treatment. The difference was significant (p<0.05). Mean body mass index which was 33.15±3.03 kg/m2 before treatment decreased to 32.22±3.1 kg/m2 after treatment. Sibutramine treatment had no adverse effects during the 15 days. Mean waist circumference changed from 89.91± 11.09 to 87.76± 3.65. No changes were observed in routine blood parameters in the patients at the end of 15 days treatment. In this study baseline mean thermogenic response was found to be 0.97±0.03 kcal/kg/h but it increased to 1.26±0.17 kcal/kg/h at the end of the 15-day sibutramine treatment (p<0.05) meaning that sibutramine treatment at a dose of 10 mg/day elevates body heat generation as early as 15 days after the beginning of treatment. This is in accordance with central efferent sympathetic effects that elevate heat generation.