Metformin in the treatment of HIV lipodystrophy syndrome - A randomized controlled trial
Metformin in the treatment of HIV lipodystrophy syndrome - A randomized controlled trial
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DOI：
10.1001/jama.284.4.472
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发表时间：
2000-07-26
影响因子：
120.7
通讯作者：
Grinspoon, S
中科院分区：
文献类型：
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作者：
Hadigan, C;Corcoran, C;Grinspoon, S
据估计，以脂肪重新分布和胰岛素抵抗为特征的脂肪营养不良综合征会影响大多数接受联合抗逆转录病毒治疗的人类免疫缺陷病毒（HIV）感染者。对于与 HIV 脂肪营养不良综合征相关的代谢紊乱，尚无经过证实的治疗方法。 目的 确定二甲双胍治疗脂肪重新分布和葡萄糖稳态异常的 HIV 感染患者的安全性和有效性。 设计和设置 1998 年 12 月至 2000 年 1 月在大学医院进行的随机、双盲、安慰剂对照试点研究，患者 26 名 HIV 感染、非糖尿病脂肪患者重新分布和异常口服葡萄糖耐量试验 (OGTT) 结果、高胰岛素血症或两者兼而有之。 干预措施 患者被随机分配接受二甲双胍，500 mg 每日两次 (n=14) 或相同的安慰剂 (n=12)，为期 3 个月。 主要结果指标 胰岛素曲线下面积 (AUC)，在基线和 3 个月随访时在 75 g OGTT 后 120 分钟计算，并在治疗之间进行比较结果 OGTT 120 分钟后，接受二甲双胍治疗的患者平均 (SEM) 胰岛素 AUC 显着降低（-2930 [912] vs -414 [432] mu IU/mL [-20349 (6334) vs -2875 {3000} pmol/L]；P=.01）、体重（-1.3 [0.6] vs 1.1[0.4] kg；分别与对照组相比，P=.005）和舒张压（-5 [4] 与 5 [2] mm Hg；P=.009）。二甲双胍治疗与腹部内脏脂肪减少（VAT；-1115 [819] vs 1191 [699] mm(2)；P=.08）和腹部皮下脂肪（SAT）成比例减少有关；与安慰剂治疗的患者相比，二甲双胍治疗的患者的 VAT-SAT 比率没有变化。二甲双胍治疗没有观察到乳酸或肝转氨酶水平增加。轻度腹泻是二甲双胍最常见的不良反应。没有患者因不良反应而停止治疗。 结论 这项研究表明，相对较低剂量的二甲双胍可降低患有脂肪营养不良的 HIV 感染患者的胰岛素抵抗和相关心血管风险参数。
Context A syndrome of lipodystrophy, characterized by fat redistribution and insulin resistance, has been estimated to affect the majority of human immunodeficiency virus (HIV)-infected individuals who are treated with combination antiretroviral therapy. There are no proven therapies for the metabolic disturbances associated with HIV lipodystrophy syndrome.Objective To determine the safety and efficacy of metformin therapy in HIV-infected patients with fat redistribution and abnormal glucose homeostasis.Design and Setting Randomized, double-blind, placebo-controlled pilot study conducted in a university hospital between December 1998 and January 2000,Patients Twenty-six HIV-infected, nondiabetic patients with fat redistribution and abnormal oral glucose tolerance test (OGTT) results, hyperinsulinemia, or both.Interventions Patients were randomly assigned to receive metformin, 500 mg twice daily (n=14), or identical placebo (n=12), for 3 months.Main Outcome Measures Insulin area under the curve (AUC), calculated 120 minutes following a 75-g OGTT at baseline vs at 3-month follow-up and compared between treatment groups.Results Patients treated with metformin demonstrated significant reductions in mean (SEM) insulin AUC 120 minutes after OGTT (-2930 [912] vs -414 [432] mu IU/mL [-20349 (6334) vs -2875 {3000} pmol/L]; P=.01), weight (-1.3 [0.6] vs 1.1[0.4] kg; P=.005), and diastolic blood pressure (-5 [4] vs 5 [2] mm Hg; P=.009) vs controls, respectively. Metformin therapy was associated with a decrease in visceral abdominal fat (VAT; -1115 [819] vs 1191 [699] mm(2); P=.08) and a proportional reduction in subcutaneous abdominal fat (SAT); the VAT-SAT ratio was unchanged in metformin-treated vs placebo-treated patients. No increase in lactate or liver transaminase levels was observed with metformin treatment. Mild diarrhea was the most common adverse effect of metformin. No patient discontinued therapy because of adverse effects.Conclusions This study suggests that a relatively low dosage of metformin reduces insulin resistance and related cardiovascular risk parameters in HIV-infected patients with lipodystrophy.