促胃液素释放肽，一种生长激素释放因子，对 HIV 感染合并腹部脂肪堆积患者的影响：一项随机安慰剂对照试验及安全性扩展研究。

Effects of tesamorelin, a growth hormone-releasing factor, in HIV-infected patients with abdominal fat accumulation: a randomized placebo-controlled trial with a safety extension.

机构信息

Department of Medicine, Montreal General Hospital and McGill University School of Medicine, Montreal, CA, USA.

出版信息

J Acquir Immune Defic Syndr. 2010 Mar;53(3):311-22. doi: 10.1097/QAI.0b013e3181cbdaff.

DOI:10.1097/QAI.0b013e3181cbdaff

PMID:20101189

Abstract

BACKGROUND

HIV-infected patients receiving antiretroviral therapy often demonstrate excess visceral fat. A growth hormone-releasing factor, tesamorelin, may selectively reduce visceral fat in this population. We investigated the effects of tesamorelin (GHRH(1-44)) in HIV-infected patients with central fat accumulation.

METHODS

A 12-month study of 404 HIV-infected patients with excess abdominal fat in the context of antiretroviral therapy was conducted between January 2007 and October 2008. The study consisted of 2 sequential phases. In the primary efficacy phase (months 0-6), patients were randomly assigned to receive tesamorelin [2 mg subcutaneous (SC) every day] or placebo in a 2:1 ratio. In the extension phase (months 6-12), patients receiving tesamorelin were rerandomized to continue on tesamorelin (2 mg SC every day) or switch to placebo. Patients initially randomized to placebo switched to tesamorelin. Patients and investigators were blinded to treatment assignment throughout the study. The primary endpoint was visceral adipose tissue (VAT). Secondary endpoints included body image, IGF-I, safety measures, including glucose, and other body composition measures.

RESULTS

VAT decreased by -10.9% (-21 cm(2)) in the tesamorelin group vs. -0.6% (-1 cm(2)) in the placebo group in the 6-month efficacy phase, P < 0.0001. Trunk fat (P < 0.001), waist circumference (P = 0.02), and waist-hip-ratio (P = 0.001) improved, with no change in limb or abdominal SC fat. Insulin-like growth factor-1 increased (P < 0.001), but no change in glucose parameters was observed. Patient rating of belly appearance distress (P = 0.02) and physician rating of belly profile (P = 0.02) were significantly improved in the tesamorelin vs. placebo-treated groups. The drug was well tolerated. VAT was reduced by approximately 18% (P < 0.001) in patients continuing tesamorelin for 12 months. The initial improvements over 6 months in VAT were rapidly lost in those switching from tesamorelin to placebo.

CONCLUSIONS

Tesamorelin reduces visceral fat by approximately 18% and improves body image distress in HIV-infected patients with central fat accumulation. These changes are achieved without significant side effects or perturbation of glucose.

摘要

背景

接受抗逆转录病毒治疗的 HIV 感染者常表现出过多的内脏脂肪。一种生长激素释放因子， tesamorelin，可能会选择性地减少这一人群的内脏脂肪。我们研究了 tesamorelin（GHRH（1-44））在有中心性脂肪堆积的 HIV 感染者中的作用。

方法

在 2007 年 1 月至 2008 年 10 月期间，进行了一项为期 12 个月的研究，共纳入 404 名接受抗逆转录病毒治疗的 HIV 感染者，这些患者的腹部脂肪过多。该研究包括两个连续阶段。在主要疗效阶段（0-6 个月），患者随机分为 tesamorelin [2 mg 皮下（SC）每天]或安慰剂组，比例为 2：1。在扩展阶段（6-12 个月），接受 tesamorelin 的患者重新随机分为继续 tesamorelin（2 mg SC 每天）或转换为安慰剂组。最初随机分配到安慰剂的患者转换为 tesamorelin。在整个研究过程中，患者和研究者均对治疗分组不知情。主要终点为内脏脂肪组织（VAT）。次要终点包括身体形象、IGF-I、安全性指标（包括血糖）和其他身体成分指标。

结果

在 6 个月的疗效期内， tesamorelin 组的 VAT 减少了-10.9%（-21cm2），而安慰剂组仅减少了-0.6%（-1cm2），两组差异具有统计学意义（P<0.0001）。躯干脂肪（P<0.001）、腰围（P=0.02）和腰臀比（P=0.001）均有所改善，而四肢和腹部皮下脂肪无变化。胰岛素样生长因子-1（IGF-1）增加（P<0.001），但血糖参数无变化。 tesamorelin 组患者对腹部外观的困扰评分（P=0.02）和医生对腹部轮廓的评分（P=0.02）均显著改善。 tesamorelin 组耐受性良好。继续 tesamorelin 治疗 12 个月后，VAT 减少约 18%（P<0.001）。在从 tesamorelin 转为安慰剂的患者中，最初 6 个月内的 VAT 快速改善迅速丧失。