Clinical Experiences

Study Objective: To determine the effect of sibutramine on body weight of patients with obesity.

Study Design And Schedule: In a large multicentric, 24-week dose-ranging placebo-controlled study 1047 patients with obesity were enrolled at seven clinical centers in USA. The patients were randomized to receive 1 of 6 doses of sibutramine (1,5,10, 15, 20 or 30 mg) or placebo once daily. A two-week placebo run-in period was used to initiate a standardized program of diet, physical activity, and life style changes.

Weight, vital signs, supine blood pressure, and pulse rate were measured at each visit (weeks 1, 2, 4, 6, 8, 10, 12, 15, 18, 21 and 24). Waist and hip circumference measurements were performed by standard procedures. Electrocardiograms (ECGs) were recorded at baseline and at weeks 1, 2, 6, 12, 18 and 24. Lipid panels were performed following an 8-hour fast at baseline and at weeks 12 and 24.

All the patients enrolled in the study, had one counseling visit by a registered dietician during 2-week run-in phase. The patients were advised exercise program of walking 20-30 min/day (3-5kcal/min) and received instructions in behavioral change techniques. The patients also received instructions for a reduced calorie diet (1,200 kcal/day for women; 1,500 kcal/day for men).

Results: A statistically significant dose related weight loss with sibutramine therapy vs. placebo (p<0.05) was observed across all time-points for a 5 mg/day to 30 mg/day dosage of sibutramine.

At 24 weeks for those who completed the study the percent weight loss from baseline was:

Placebo - 1.2%

1mg - 2.7%

5 mg - 3.9%

10 mg - 6.1%

15 mg - 7.4%

20 mg - 8.8%

30 mg - 9.4%

It was thus observed that weight loss was dose dependent and was greatest during the first 12 weeks. Weight loss achieved at week 4 was predictive of of weight loss achieved at week 24. Waist and hip circumferences were significantly decreased vs placebo for doses above 10 mg (p<0.05). Patients losing weight showed an increase in high density lipoprotein (HDL) cholesterol and reductions in serum triglycerides, total cholesterol, low density lipoprotein (LDL) cholesterol and uric acid.

Most common treatment-related adverse events were dry mouth, anorexia and insomnia. A small mean increase in blood pressure and pulse rate (with considerable individual variability) were observed in patients treated with sibutramine.

Conclusion: In the treatment of uncomplicated obesity sibutramine administered once daily for a period of 24 weeks produced dose-related weight loss. Improvements in serum lipids and uric acid were observed to accompany sibutramine-induced weight loss.