Use of Twice-Daily Exenatide in Basal Insulin-Treated Patients With Type 2 Diabetes A Randomized, Controlled Trial
Use of Twice-Daily Exenatide in Basal Insulin-Treated Patients With Type 2 Diabetes A Randomized, Controlled Trial
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DOI：
10.7326/0003-4819-154-2-201101180-00300
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发表时间：
2011-01-18
影响因子：
39.2
通讯作者：
Rosenstock, Julio
中科院分区：
文献类型：
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作者：
Buse, John B.;Bergenstal, Richard M.;Rosenstock, Julio
背景资料：糖尿病的胰岛素替代治疗通常需要膳食干预以达到血红蛋白A（1c）（HbA（1c））的目标。目的：在接受甘精胰岛素治疗的患者中，测试每日两次艾塞那肽注射是否比安慰剂更能降低HbA（1c）水平。设计：平行、随机、安慰剂对照试验，按HbA（1c）水平在研究中心进行区组和分层，从2008年10月至2010年1月进行。参与者、研究者和进行研究的人员对治疗分配设盲。（ClinicalTrials.gov注册号：NCT 00765817）设置：5个国家的59个中心。患者：HbA（1c）水平为7.1%-10.5%的2型糖尿病成人，接受甘精胰岛素单药治疗或与二甲双胍或吡格列酮（或两种药物）联合治疗。干预：通过一个集中的、计算机生成的、随机序列交互式语音应答系统分配给exenglutamine，10 μ g，每日两次，或安慰剂，持续30周。主要结局是HbA（1c）水平的变化。次要结果包括HbA（1c）值为7.0%或更低和6.5%或更低的参与者百分比，7点自我监测血糖曲线，体重，腰围，胰岛素剂量，低血糖和不良事件。艾塞那肽组HbA（1c）水平降低1.74%，安慰剂组降低1.04%（组间差异，-0.69% [95%CI，-0.93%至-0.46%]; P < 0.001）。艾塞那肽组体重下降1.8 kg，安慰剂组体重增加1.0 kg（组间差异，-2.7 kg [CI，-3.7至-1.7]）。艾塞那肽组和安慰剂组胰岛素剂量平均增加13 U/d和20 U/d。两组间轻度低血糖的估计发生率相似。13名exenglutamine接受者和1名安慰剂接受者因不良事件而终止研究（P < 0.010）;恶心发生率（41% vs. 8%），腹泻（18% vs. 8%），呕吐（18%对4%）、头痛（14%对4%）和便秘（10%对2%）的发生率高于安慰剂组。基线时组间在性别、伴随降糖药物的使用和HbA（1c）水平方面存在轻微失衡，更多的艾塞那肽接受者比安慰剂接受者因不良事件而退出研究。结论：在接受甘精胰岛素治疗的未受控制的2型糖尿病患者中，添加每日两次艾塞那肽注射可改善血糖控制，而不会增加低血糖或体重增加。艾塞那肽的不良反应包括恶心、腹泻、呕吐、头痛和便秘。Ann Intern Med.2011;154：103-112.
Background: Insulin replacement in diabetes often requires prandial intervention to reach hemoglobin A(1c) (HbA(1c)) targets.Objective: To test whether twice-daily exenatide injections reduce HbA(1c) levels more than placebo in people receiving insulin glargine.Design: Parallel, randomized, placebo-controlled trial, blocked and stratified by HbA(1c) level at site, performed from October 2008 to January 2010. Participants, investigators, and personnel conducting the study were masked to treatment assignments. (ClinicalTrials.gov registration number: NCT00765817)Setting: 59 centers in 5 countries.Patients: Adults with type 2 diabetes and an HbA(1c) level of 7.1% to 10.5% who were receiving insulin glargine alone or in combination with metformin or pioglitazone (or both agents).Intervention: Assignment by a centralized, computer-generated, random-sequence interactive voice-response system to exenatide, 10 mu g twice daily, or placebo for 30 weeks.Measurements: The primary outcome was change in HbA(1c) level. Secondary outcomes included the percentage of participants with HbA(1c) values of 7.0% or less and 6.5% or less, 7-point self-monitored glucose profiles, body weight, waist circumference, insulin dose, hypoglycemia, and adverse events.Results: 112 of 138 exenatide recipients and 101 of 123 placebo recipients completed the study. The HbA(1c) level decreased by 1.74% with exenatide and 1.04% with placebo (between-group difference, -0.69% [95% CI, -0.93% to -0.46%]; P < 0.001). Weight decreased by 1.8 kg with exenatide and increased by 1.0 kg with placebo (between-group difference, -2.7 kg [CI, -3.7 to -1.7]). Average increases in insulin dosage with exenatide and placebo were 13 U/d and 20 U/d. The estimated rate of minor hypoglycemia was similar between groups. Thirteen exenatide recipients and 1 placebo recipient discontinued the study because of adverse events (P < 0.010); rates of nausea (41% vs. 8%), diarrhea (18% vs. 8%), vomiting (18% vs. 4%), headache (14% vs. 4%), and constipation (10% vs. 2%) were higher with exenatide than with placebo.Limitations: The study was of short duration. There were slight imbalances between groups at baseline in terms of sex, use of concomitant glucose-lowering medications, and HbA(1c) levels, and more exenatide recipients than placebo recipients withdrew because of adverse events.Conclusion: Adding twice-daily exenatide injections improved glycemic control without increased hypoglycemia or weight gain in participants with uncontrolled type 2 diabetes who were receiving insulin glargine treatment. Adverse events of exenatide included nausea, diarrhea, vomiting, headache, and constipation.Primary Funding Source: Alliance of Eli Lilly and Company and Amylin Pharmaceuticals. Ann Intern Med. 2011;154:103-112.