西布曲明可产生与剂量相关的体重减轻。

Sibutramine produces dose-related weight loss.

作者信息

Bray G A, Blackburn G L, Ferguson J M, Greenway F L, Jain A K, Mendel C M, Mendels J, Ryan D H, Schwartz S L, Scheinbaum M L, Seaton T B

机构信息

Pennington Biomedical Research Center, Baton Rouge, LA 70808, USA.

出版信息

Obes Res. 1999 Mar;7(2):189-98. doi: 10.1002/j.1550-8528.1999.tb00701.x.

DOI:10.1002/j.1550-8528.1999.tb00701.x

PMID:10102256

Abstract

OBJECTIVE

Sibutramine is a weight control drug that inhibits the reuptake of both serotonin and norepinephrine. In animals, it reduces food intake and increases thermogenesis and preliminary data in human beings showed weight loss. This paper reports a 24-week dose-ranging study to determine the effect of sibutramine on body weight of patients with obesity.

RESEARCH METHODS AND PROCEDURES

Seven clinical centers screened 1463 patients with obesity and randomized 1047 to 24 weeks of treatment with 1 of 6 doses 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 activity, and lifestyle changes.

RESULTS

Weight loss was dose-related and statistically significant vs. placebo (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 was: 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 weight loss achieved at week 24. Patients losing weight demonstrated an increase in serum high density lipoprotein cholesterol and reductions in serum triglycerides, total cholesterol, low density lipoprotein cholesterol, and uric acid. Small mean increases in blood pressure and pulse rate (with considerable individual variability) were observed in patients treated with sibutramine. The most frequent adverse events were dry mouth, anorexia, and insomnia.

DISCUSSION

Sibutramine administered once daily for 24 weeks in the weight loss phase of treatment for uncomplicated obesity produced dose-related weight loss and was well tolerated. Improvements in serum lipids and uric acid accompany sibutramine-induced weight loss. Most of the adverse events observed on sibutramine are related to its pharmacology, including small mean increases in blood pressure and heart rate.

摘要

目的

西布曲明是一种体重控制药物，可抑制血清素和去甲肾上腺素的再摄取。在动物实验中，它能减少食物摄入量并增加产热，人体的初步数据显示其可导致体重减轻。本文报告了一项为期24周的剂量范围研究，以确定西布曲明对肥胖患者体重的影响。

研究方法与步骤

7个临床中心筛选了1463例肥胖患者，并将1047例患者随机分为6组，分别接受6种剂量（1、5、10、15、20或30毫克）的西布曲明或安慰剂治疗，为期24周，每日服用1次。683例患者完成了研究。采用为期两周的安慰剂导入期，以启动标准化的饮食、体育活动和生活方式改变计划。

结果

对于5毫克/天至30毫克/天剂量的西布曲明，在所有时间点，体重减轻与剂量相关，且与安慰剂相比具有统计学意义（p<0.05）。在第24周时，完成治疗者相对于基线的体重减轻百分比为：安慰剂组1.2%；1毫克组2.7%；5毫克组3.9%；10毫克组6.1%；15毫克组7.4%；20毫克组8.8%；30毫克组9.4%。第4周时的体重减轻情况可预测第24周时的体重减轻情况。体重减轻的患者血清高密度脂蛋白胆固醇升高，血清甘油三酯、总胆固醇、低密度脂蛋白胆固醇和尿酸降低。服用西布曲明的患者血压和脉搏率平均有小幅升高（个体差异较大）。最常见的不良事件为口干、厌食和失眠。