Program in Nutritional Metabolism, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA.
Clin Infect Dis. 2012 Jun;54(11):1642-51. doi: 10.1093/cid/cis251. Epub 2012 Apr 10.
Tesamorelin, a growth hormone-releasing hormone analogue, decreases visceral adipose tissue (VAT) by 15%-20% over 6-12 months in individuals with human immunodeficiency virus (HIV)-associated abdominal adiposity, but it is unknown whether VAT reduction is directly associated with endocrine and metabolic changes.
In 2 phase III, randomized, double-blind studies, men and women with HIV-associated abdominal fat accumulation were randomly assigned (ratio, 2:1) to receive tesamorelin or placebo for 26 weeks. At week 26, patients initially receiving tesamorelin were randomly assigned to continue receiving tesamorelin or to receive placebo for an additional 26 weeks. In per-protocol analysis of 402 subjects initially randomly assigned to receive tesamorelin, those with ≥8% reduction in VAT were defined a priori as responders per the statistical analysis plan. Post hoc analyses were performed to assess differences between responders and nonresponders.
Compared with tesamorelin nonresponders, responders experienced greater mean (±SD) reduction in triglyceride levels (26 weeks: -0.6 ± 1.7 mmol/L vs -0.1 ± 1.2 mmol/L [P = .005]; 52 weeks: -0.8 ± 1.8 mmol/L vs 0.0 ± 1.1 mmol/L [P = .003]) and attenuated changes in fasting glucose levels (26 weeks: 1 ± 16 mg/dL vs 5 ± 14 mg/dL [P = .01]; 52 weeks: -1 ± 14 mg/dL vs 8 ± 17 mg/dL [P < .001]), hemoglobin A1c levels (26 weeks: 0.1 ± 0.3% vs 0.3 ± 0.4% [P < .001]; 52 weeks: 0.0 ± 0.3% vs 0.2 ± 0.5% [P = .003]), and other parameters of glucose homeostasis. Similar patterns were seen for adiponectin levels, with significant improvement in responders vs nonresponders. Changes in lipid levels and glucose homeostasis were significantly associated with percentage change in VAT.
In contrast to nonresponders, HIV-infected patients receiving tesamorelin with ≥8% reduction in VAT have significantly improved triglyceride levels, adiponectin levels, and preservation of glucose homeostasis over 52 weeks of treatment. CLINICALTRIALS.GOV REGISTRATION: NCT00123253, NCT00435136, NCT00608023.
特索瑞林是一种生长激素释放激素类似物，可在 6-12 个月内使人类免疫缺陷病毒（HIV）相关腹部肥胖个体的内脏脂肪组织（VAT）减少 15%-20%，但尚不清楚 VAT 减少是否与内分泌和代谢变化直接相关。
在 2 项随机、双盲、3 期研究中，随机分配（比例为 2:1）有 HIV 相关腹部脂肪堆积的男性和女性接受特索瑞林或安慰剂治疗 26 周。在第 26 周时，最初接受特索瑞林治疗的患者被随机分配继续接受特索瑞林或在另外 26 周内接受安慰剂治疗。在最初随机分配接受特索瑞林治疗的 402 名患者的方案分析中，根据统计分析计划，将 VAT 减少≥8%的患者预先定义为应答者。进行了事后分析以评估应答者与无应答者之间的差异。
与特索瑞林无应答者相比，应答者的甘油三酯水平平均（±SD）降低幅度更大（26 周：-0.6±1.7mmol/L 与-0.1±1.2mmol/L[P=0.005]；52 周：-0.8±1.8mmol/L 与 0.0±1.1mmol/L[P=0.003]），空腹血糖水平的变化也减弱（26 周：1±16mg/dL 与 5±14mg/dL[P=0.01]；52 周：-1±14mg/dL 与 8±17mg/dL[P<.001]），血红蛋白 A1c 水平（26 周：0.1±0.3%与 0.3±0.4%[P<.001]；52 周：0.0±0.3%与 0.2±0.5%[P=0.003]），以及葡萄糖稳态的其他参数。脂联素水平也呈现出类似的模式，应答者与无应答者相比有显著改善。血脂水平和葡萄糖稳态的变化与 VAT 百分比变化显著相关。
与无应答者相比，接受特索瑞林治疗且 VAT 减少≥8%的 HIV 感染患者在 52 周的治疗过程中，甘油三酯水平、脂联素水平显著改善，且葡萄糖稳态得到维持。
临床试验.gov 注册号：NCT00123253、NCT00435136、NCT00608023。
