University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Lancet. 2013 Jan 12;381(9861):117-24. doi: 10.1016/S0140-6736(12)61267-7. Epub 2012 Nov 7.
Glucagon-like peptide-1 receptor agonists exenatide and liraglutide have been shown to improve glycaemic control and reduce bodyweight in patients with type 2 diabetes. We compared the efficacy and safety of exenatide once weekly with liraglutide once daily in patients with type 2 diabetes.
We did a 26 week, open-label, randomised, parallel-group study at 105 sites in 19 countries between Jan 11, 2010, and Jan 17, 2011. Patients aged 18 years or older with type 2 diabetes treated with lifestyle modification and oral antihyperglycaemic drugs were randomly assigned (1:1), via a computer-generated randomisation sequence with a voice response system, to receive injections of once-daily liraglutide (1·8 mg) or once-weekly exenatide (2 mg). Participants and investigators were not masked to treatment assignment. The primary endpoint was change in glycated haemoglobin (HbA(1c)) from baseline to week 26. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01029886.
Of 912 randomised patients, 911 were included in the intention-to-treat analysis (450 liraglutide, 461 exenatide). The least-squares mean change in HbA(1c) was greater in patients in the liraglutide group (-1·48%, SE 0·05; n=386) than in those in the exenatide group (-1·28%, 0·05; 390) with the treatment difference (0·21%, 95% CI 0·08-0·33) not meeting predefined non-inferiority criteria (upper limit of CI <0·25%). The most common adverse events were nausea (93 [21%] in the liraglutide group vs 43 [9%] in the exenatide group), diarrhoea (59 [13%] vs 28 [6%]), and vomiting 48 [11%] vs 17 [4%]), which occurred less frequently in the exenatide group and with decreasing incidence over time in both groups. 24 (5%) patients allocated to liraglutide and 12 (3%) allocated to exenatide discontinued participation because of adverse events.
Both once daily liraglutide and once weekly exenatide led to improvements in glycaemic control, with greater reductions noted with liraglutide. These findings, plus differences in injection frequency and tolerability, could inform therapeutic decisions for treatment of patients with type 2 diabetes.
Eli Lilly and Company and Amylin Pharmaceuticals LLC.
胰高血糖素样肽-1 受体激动剂艾塞那肽和利拉鲁肽已被证明可改善 2 型糖尿病患者的血糖控制并减轻体重。我们比较了每周一次给予艾塞那肽与每日一次给予利拉鲁肽在 2 型糖尿病患者中的疗效和安全性。
我们于 2010 年 1 月 11 日至 2011 年 1 月 17 日在 19 个国家的 105 个地点进行了一项 26 周的、开放标签、随机、平行分组研究。年龄在 18 岁或以上的 2 型糖尿病患者接受生活方式改变和口服降糖药物治疗，通过计算机生成的随机序列和语音应答系统以 1:1 的比例随机分配接受每日一次利拉鲁肽（1.8mg）或每周一次艾塞那肽（2mg）注射。参与者和研究者未对治疗分配进行盲法。主要终点是从基线到第 26 周时糖化血红蛋白（HbA1c）的变化。分析采用意向治疗。该试验在 ClinicalTrials.gov 注册，编号为 NCT01029886。
在 912 名随机患者中，911 名患者被纳入意向治疗分析（利拉鲁肽组 450 名，艾塞那肽组 461 名）。利拉鲁肽组患者的 HbA1c 平均变化较艾塞那肽组（-1.48%，0.05；n=386）更大（-1.28%，0.05；390），治疗差异（0.21%，95%CI 0.08-0.33）未达到预先设定的非劣效性标准（上限<0.25%）。最常见的不良反应为恶心（利拉鲁肽组 93 [21%] vs 艾塞那肽组 43 [9%]）、腹泻（59 [13%] vs 28 [6%]）和呕吐（48 [11%] vs 17 [4%]），这些不良反应在艾塞那肽组中发生频率较低，且两组不良反应的发生率随时间推移而降低。24 名（5%）被分配接受利拉鲁肽治疗的患者和 12 名（3%）被分配接受艾塞那肽治疗的患者因不良反应而退出。
每日一次的利拉鲁肽和每周一次的艾塞那肽均可改善血糖控制，利拉鲁肽的改善效果更显著。这些发现，加上注射频率和耐受性方面的差异，可为 2 型糖尿病患者的治疗决策提供信息。
礼来公司和艾塞那肽制药公司。
