Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes
Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes
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DOI：
10.2337/diacare.28.5.1092
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发表时间：
2005-05-01
期刊：
影响因子：
16.2
通讯作者：
Baron, AD
中科院分区：
文献类型：
--
作者：
DeFronzo, RA;Ratner, RE;Baron, AD
目的 - 本研究评估了肠促胰岛素模拟物艾塞那肽 (exendin-4) 改善使用最大有效二甲双胍剂量未能实现血糖控制的 2 型糖尿病患者血糖控制的能力。 研究设计和方法 - 在美国 82 个地点对 336 名随机患者进行了一项三盲、安慰剂对照、为期 30 周的研究。总共有 272 名患者完成了这项研究。意向治疗人群基线为 53 +/- 10 年，BMI 为 34.2 +/- 5.9 kg/m(2)，HbA1c 为 8.2 +/- 1.1%。安慰剂治疗 4 周后，受试者自行皮下注射 5 mg 艾塞那肽或安慰剂，每天两次，持续 4 周，然后每天两次皮下注射 5 或 10 μg 艾塞那肽或安慰剂，持续 26 周。所有受试者均继续二甲双胍治疗。 结果 - 在第 30 周，每组的 HbA1c 相对于基线 +/- SE 的变化分别为 -0.78 +/- 0.10% (10 μg)、-0.40 +/- 0.11% (5 μg) 和 +0.08 +/- 0.10%（安慰剂；意向治疗；调整后 P < 0.002）。在可评估受试者中，46%（10 μg）、32%（5 μg）和 13%（安慰剂）的 HbA1c 达到 7%（与安慰剂相比，P < 0.01）。艾塞那肽治疗受试者表现出进行性剂量依赖性体重减轻（-2.8 +/- 0.5 kg [10 μg]，-1.6 +/- 0.4 kg [5 μg]；与安慰剂相比，P < 0.001）。最常见的不良事件是胃肠道反应，一般为轻度至中度。轻度至中度低血糖的发生率较低，并且各治疗组相似，没有严重低血糖。结论 - 对于未能用二甲双胍实现血糖控制的 2 型糖尿病患者，艾塞那肽总体耐受性良好，可降低 HbA1c，且体重不增加，低血糖发生率也没有增加。
OBJECTIVE - This study evaluates the ability of the incretin mimetic exenatide (exendin-4) to improve glycemic control in patients with type 2 diabetes failing to achieve glycemic control with maximally effective metformin doses.RESEARCH DESIGN AND METHODS - A triple-blind, placebo-controlled, 30-week study at 82 U.S. sites was performed with 336 randomized patients. In all, 272 patients completed the study. The intent-to-treat population baseline was 53 +/- 10 years with BMI of 34.2 +/- 5.9 kg/m(2) and HbA1c of 8.2 +/- 1.1%. After 4 weeks of placebo, subjects self-administered 5 mg exenatide or placebo subcutaneously twice daily for 4 weeks followed by 5 or 10 mu g exenatide, or placebo subcutaneously twice daily for 26 weeks. All subjects continued metformin therapy.RESULTS - At week 30, HbA1c changes from baseline +/- SE for each group were -0.78 +/- 0.10% (10 mu g), -0.40 +/- 0.11% (5 mu g), and +0.08 +/- 0.10% (placebo; intent to treat; adjusted P < 0.002). Of evaluable subjects, 46% (10 mu g), 32% (5 mu g), and 13% (placebo) achieved HbA1c 7% (P < 0.01 vs. placebo). Exenatide-treated subjects displayed progressive dose-dependent weight loss (-2.8 +/- 0.5 kg [10 mu g], -1.6 +/- 0.4 kg [5 mu g]; P < 0.001 vs. placebo). The most frequent adverse events were gastrointestinal in nature and generally mild to moderate. Incidence of mild to moderate hypoglycemia was low and similar across treatment arms, with no severe hypoglycemia.CONCLUSIONS - Exenatide was generally well tolerated and reduced HbA1c with no weight gain and no increased incidence of hypoglycemia in patients with type 2 diabetes failing to achieve glycemic control with metformin.