University of North Carolina School of Medicine, Chapel Hill, 27599, USA.
Ann Intern Med. 2011 Jan 18;154(2):103-12. doi: 10.7326/0003-4819-154-2-201101180-00300. Epub 2010 Dec 6.
Insulin replacement in diabetes often requires prandial intervention to reach hemoglobin A₁(c) (HbA₁(c)) targets.
To test whether twice-daily exenatide injections reduce HbA₁(c) levels more than placebo in people receiving insulin glargine.
Parallel, randomized, placebo-controlled trial, blocked and stratified by HbA₁(c) 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)
59 centers in 5 countries.
Adults with type 2 diabetes and an HbA₁(c) level of 7.1% to 10.5% who were receiving insulin glargine alone or in combination with metformin or pioglitazone (or both agents).
Assignment by a centralized, computer-generated, random-sequence interactive voice-response system to exenatide, 10 µg twice daily, or placebo for 30 weeks.
The primary outcome was change in HbA₁(c) level. Secondary outcomes included the percentage of participants with HbA₁(c) 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.
112 of 138 exenatide recipients and 101 of 123 placebo recipients completed the study. The HbA₁(c) 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.
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 HbA₁(c) levels, and more exenatide recipients than placebo recipients withdrew because of adverse events.
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.
Alliance of Eli Lilly and Company and Amylin Pharmaceuticals.
糖尿病患者的胰岛素替代治疗通常需要餐前干预才能达到血红蛋白 A₁(c)（HbA₁(c)）目标。
检验每日两次给予艾塞那肽能否比安慰剂更有效地降低正在接受甘精胰岛素治疗的人群的 HbA₁(c)水平。
这是一项平行、随机、安慰剂对照试验，按试验地点的 HbA₁(c)水平分层和分组，于 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均设盲。（临床试验注册编号：NCT00765817）
5 个国家的 59 个中心。
HbA₁(c)水平为 7.1%~10.5%的 2 型糖尿病成人患者，正在接受甘精胰岛素单独或与二甲双胍或吡格列酮（或两者合用）联合治疗。
通过中央、计算机生成的、交互式语音应答系统，以 10 µg 每日 2 次的艾塞那肽或安慰剂进行随机分组，疗程为 30 周。
主要终点为 HbA₁(c)水平的变化。次要终点包括 HbA₁(c)值达到 7.0%或更低和 6.5%或更低的参与者比例、7 点自我监测血糖谱、体重、腰围、胰岛素剂量、低血糖和不良事件。
138 名艾塞那肽接受者中有 112 名和 123 名安慰剂接受者完成了研究。艾塞那肽组 HbA₁(c)水平下降 1.74%，安慰剂组下降 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 1.8kg，安慰剂组体重增加 1.0kg（组间差异，-2.7kg[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 13U/d 和 20U/d。两组的轻度低血糖发生率估计相似。13 名艾塞那肽接受者和 1 名安慰剂接受者因不良事件（P<0.010）退出研究；艾塞那肽组发生恶心（41%比 8%）、腹泻（18%比 8%）、呕吐（18%比 4%）、头痛（14%比 4%）和便秘（10%比 2%）的频率高于安慰剂组。
研究持续时间较短。两组在基线时的性别、同时使用的降血糖药物以及 HbA₁(c)水平方面存在轻微不平衡，并且由于不良事件，更多的艾塞那肽接受者比安慰剂接受者退出了研究。
在接受甘精胰岛素治疗的控制不佳的 2 型糖尿病患者中，每日两次给予艾塞那肽可改善血糖控制，而不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。
礼来公司和安斯泰来制药公司的联盟。
