右旋芬氟拉明治疗肥胖症：一项双盲试验及试验后随访

Dexfenfluramine treatment of obesity: a double blind trial with post trial follow up.

作者信息

O'Connor H T, Richman R M, Steinbeck K S, Caterson I D

机构信息

Department of Endocrinology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia.

出版信息

Int J Obes Relat Metab Disord. 1995 Mar;19(3):181-9.

PMID:7780494

Abstract

OBJECTIVE

As successful weight management demands a long term approach, a better understanding of weight changes during and for significant periods after cessation of dexfenfluramine therapy is essential to the evaluation of the drug's effectiveness in clinical practice. This study aimed to investigate additional benefits to weight loss during 6 months treatment with dexfenfluramine in 60 patients enrolled in a weight loss programme.

DESIGN

Sixty obese subjects (21 males; 39 females) were randomised to dexfenfluramine (15 mg twice daily) or placebo for six months. Fifty one (27 dexfenfluramine; 24 placebo) subjects completed the double blind, randomised, placebo controlled clinical trial.

RESULTS

After a one month 'run in' phase and six months treatment, weight loss in the dexfenfluramine group was significantly greater than placebo, 9.7 +/- 1.1 kg vs 4.9 +/- 0.9 kg (mean +/- s.e.m.); P = 0.002. Reduction in body fat, 5.0 +/- 0.7 kg vs 1.0 +/- 0.9 kg; P = 0.002 and waist circumference, 10.5 +/- 1.9 cm vs 5.7 +/- 1.1 cm; P = 0.04 was also greater in the dexfenfluramine group. Despite significant weight loss, waist to hip ratio (WHR) did not change in either group. The dexfenfluramine group reported a significantly greater incidence of nausea, dry mouth and dizziness which tended to decrease as treatment progressed. No subjects withdrew due to drug induced side effects. Reduction in serum triglyceride levels and an increase in HDL cholesterol (in female subjects) in conjunction with a reduction in fasting insulin, collectively support an improved cardiovascular risk profile in the dexfenfluramine group. Despite significant weight loss, these risk factor measurements worsened in the placebo group. After cessation of dexfenfluramine therapy, there was a significantly greater weight regain indicating a loss of treatment effect. By 5 months after cessation of dexfenfluramine, the treatment effect was negated with weight loss in the dexfenfluramine (6.0 +/- 1.6 kg) and placebo (6.2 +/- 1.3 kg) group, similar.

CONCLUSION

The results of this study support the longer term use of dexfenfluramine therapy for patients with chronic obesity.

摘要

目的

由于成功的体重管理需要长期的方法，因此更好地了解右芬氟拉明治疗期间及停药后相当长一段时间内的体重变化，对于评估该药物在临床实践中的有效性至关重要。本研究旨在调查参与减肥计划的60例患者在接受右芬氟拉明6个月治疗期间，除体重减轻之外的其他益处。

设计

60名肥胖受试者（21名男性；39名女性）被随机分为接受右芬氟拉明（每日两次，每次15毫克）或安慰剂治疗6个月。51名受试者（27名接受右芬氟拉明治疗；24名接受安慰剂治疗）完成了这项双盲、随机、安慰剂对照的临床试验。

结果

经过1个月的“导入期”和6个月的治疗后，右芬氟拉明组的体重减轻显著大于安慰剂组，分别为9.7±1.1千克和4.9±0.9千克（均值±标准误）；P = 0.002。右芬氟拉明组的体脂减少量为5.0±0.7千克，安慰剂组为1.0±0.9千克；P = 0.002，腰围减少量分别为10.5±1.9厘米和5.7±1.1厘米；P = 0.04，右芬氟拉明组也更大。尽管体重显著减轻，但两组的腰臀比（WHR）均未改变。右芬氟拉明组报告的恶心、口干和头晕发生率显著更高，且随着治疗进展有下降趋势。没有受试者因药物引起的副作用而退出。右芬氟拉明组血清甘油三酯水平降低、高密度脂蛋白胆固醇升高（女性受试者），同时空腹胰岛素降低，共同表明该组心血管风险状况有所改善。尽管体重显著减轻，但安慰剂组的这些风险因素指标却恶化了。右芬氟拉明治疗停止后，体重反弹明显更大，表明治疗效果丧失。到右芬氟拉明停药后5个月时，右芬氟拉明组（6.0±1.6千克）和安慰剂组（6.2±1.3千克）的体重减轻情况相似，治疗效果被抵消。