Nauck Michael A, Stewart Murray W, Perkins Christopher, Jones-Leone Angela, Yang Fred, Perry Caroline, Reinhardt Rickey R, Rendell Marc
St Josef Hospital (Ruhr-Universität Bochum), Gudrunstr. 56, D-44791, Bochum, Germany.
GlaxoSmithKline, King of Prussia, PA, USA.
Diabetologia. 2016 Feb;59(2):266-74. doi: 10.1007/s00125-015-3795-1. Epub 2015 Nov 17.
AIMS/HYPOTHESIS: Additional safe and effective therapies for type 2 diabetes are needed, especially ones that do not cause weight gain and have a low risk of hypoglycaemia. The present study evaluated albiglutide as monotherapy.
In this placebo-controlled study, 309 patients (aged ≥ 18 years) with type 2 diabetes inadequately controlled by diet and exercise and who were not using a glucose-lowering agent (HbA1c 7.0-10.0% [53.00-85.79 mmol/mol], body mass index 20-45 kg/m(2), and fasting C-peptide ≥ 0.26 nmol/l) were randomised (1:1:1 on a fixed randomisation schedule using an interactive voice response system) to receive once-weekly albiglutide 30 mg (n = 102) or 50 mg (n = 102) or matching placebo (n = 105). The study treatments were blinded to both patients and study personnel. All study data were collected at individual patient clinic visits. The primary efficacy endpoint was change in HbA1c from baseline to week 52. The primary analysis was applied to the intent-to-treat population. Additional efficacy and safety endpoints were assessed.
At week 52, both albiglutide 30 mg and 50 mg were superior to placebo in reducing HbA1c. The least-squares means treatment difference from placebo was -0.84% (95% CI -1.11%, -0.58%; p < 0.0001) with albiglutide 30 mg and -1.04% (-1.31%, -0.77%; p < 0.0001) with albiglutide 50 mg. Injection-site reactions were reported more frequently with albiglutide (30 mg: 17.8%; 50 mg: 22.2%) than with placebo (9.9%). Other commonly reported adverse events included nausea, diarrhoea, vomiting and hypoglycaemia; the incidences of these were generally similar across treatment groups.
CONCLUSIONS/INTERPRETATION: Albiglutide is safe and effective as monotherapy and significantly lowered HbA1c levels over 52 weeks, did not cause weight gain, and had good gastrointestinal tolerability and a low rate of hypoglycaemia compared with placebo. Trial registration ClinicalTrials.gov NCT00849017 Funding This study was sponsored by GlaxoSmithKline.
目的/假设：需要更多用于2型糖尿病的安全有效的治疗方法，尤其是那些不会导致体重增加且低血糖风险低的方法。本研究评估了阿必鲁肽作为单一疗法的效果。
在这项安慰剂对照研究中，309例年龄≥18岁、经饮食和运动控制不佳且未使用降糖药物的2型糖尿病患者（糖化血红蛋白7.0 - 10.0% [53.00 - 85.79 mmol/mol]，体重指数20 - 45 kg/m²，空腹C肽≥0.26 nmol/l）被随机分组（使用交互式语音应答系统按固定随机方案1:1:1），接受每周一次的阿必鲁肽30 mg（n = 102）或50 mg（n = 102）或匹配的安慰剂（n = 105）。研究治疗对患者和研究人员均设盲。所有研究数据在患者个体门诊就诊时收集。主要疗效终点是从基线到第52周糖化血红蛋白的变化。主要分析应用于意向性治疗人群。评估了其他疗效和安全性终点。
在第52周时，阿必鲁肽30 mg和50 mg在降低糖化血红蛋白方面均优于安慰剂。与安慰剂相比，阿必鲁肽30 mg的最小二乘均值治疗差异为 -0.84%（95%CI -1.11%，-0.58%；p < 0.0001），阿必鲁肽50 mg为 -1.04%（-1.31%，-0.77%；p < 0.0001）。与安慰剂（9.9%）相比，阿必鲁肽（30 mg：17.8%；50 mg：22.2%）注射部位反应报告更频繁。其他常见报告的不良事件包括恶心、腹泻、呕吐和低血糖；这些事件的发生率在各治疗组中总体相似。
结论/解读：阿必鲁肽作为单一疗法安全有效，在52周内显著降低糖化血红蛋白水平，不导致体重增加，与安慰剂相比具有良好的胃肠道耐受性和低血糖发生率。试验注册ClinicalTrials.gov NCT00849017 资助本研究由葛兰素史克公司赞助。
