Sibutramine produces dose-related weight loss

Objective: Sibutramine is a weight control drug that inhibits the reuptake of both serotonin and norepinephrine. In animals, it reduces food intake an d increases thermogenesis and preliminary data in human beings showed weigh t lass. This paper reports a 24-week dose-ranging study to determine the ef fect of sibutramine on body weight of patients with obesity. Research Methods nod Procedures: Seven clinical centers screened 1463 patie nts with obesity and randomized 1047 to 24 weeks of treatment with I of 6 d oses of sibutramine (1, 5, 10, 15, 20, or 30 mg) or placebo once daily. Six hundred eighty-three patients completed the study. A two-week placebo run- in period was used to initiate a standardized program of diet, physical act ivity, and lifestyle changes. Results: Weight loss was dose-related and statistically significant vs. pla cebo (p<0.05) across all time-points for a 5 mg/day to 30 mg/day dosage of sibutramine. At week 24, percent weight loss from baseline for completers w as: placebo, 1.2%; 1 mg, 2.7%; 5 mg, 3.9%; 10 mg, 6.1%; 15 mg, 7.4%; 20 mg, 8.8%; and 30 mg, 9.4%. Weight loss achieved at week 4 was predictive of we ight loss achieved at week 24. Patients losing weight demonstrated an incre ase in serum high density lipoprotein cholesterol and reductions in serum t riglycerides, total cholesterol, low density lipoprotein cholesterol, and u ric acid. Small mean increases in blood pressure and pulse rate (with consi derable individual variability) were observed in patients treated with sibu tramine. The most frequent adverse events were dry mouth, anorexia, and ins omnia. Discussion: Sibutramine administered once daily for 24 weeks in the weight loss phase of treatment for uncomplicated obesity produced dose-related wei ght loss and was well tolerated. Improvements in serum lipids and uric acid accompany sibutramine-induced weight loss. Most of the adverse events obse rved on sibutramine are related to its pharmacology, including small mean i ncreases in blood pressure and heart rate.