Obesity treatment with a progressive clinical tri-therapy combining sibutramine and a supervised diet-exercise intervention

OBJECTIVE: Sibutramine favors a negative energy balance and also has the potential to increase heart rate and blood pressure. We investigated if a progressive supervised sibutramine - diet- exercise clinical intervention could increase the body weight loss previously reported while minimizing the potential cardiostimulatory effects of this drug. DESIGN AND SUBJECTS: The tri-therapy intervention was divided into two phases of 6 weeks each in which sibutramine (10 mg) was taken once daily by eight obese men (body mass index (BMI) between 30 and 40 kg/m(2)). Part A consisted of a dietary follow-up with an energy restriction, whereas in part B an aerobic exercise program combined with a low-fat diet was introduced. Systolic (SBP) and diastolic (DBP) blood pressure, resting heart rate (RHR) and body weight were measured every 2 weeks while body density, resting metabolic rate (RMR) and respiratory quotient (RQ) were determined before and after the intervention. RESULTS: This clinical intervention produced a substantial body weight loss (-10.7 kg, P < 0.01) which was about twice as much as other 12-week studies. In part A, both RHR (+4 beats/min) and DBP (+5 mmHg, P < 0.01) were increased. However, after part B, RHR (-8 beats/min, P = 0.02) and DBP (- 3 mmHg, P < 0.01) were significantly decreased. RMR was decreased at the end of the program but this effect did not persist after adjustments for fat-free mass. RQ was also reduced (- 0.05, P < 0.01) following the clinical tri-therapy. CONCLUSION: In conclusion, these observations suggest that this clinical tri-therapy favored a satisfactory benefit- risk profile since it enhanced weight loss without inducing increases in heart rate and blood pressure or detrimental changes in RMR and substrate oxidation.