Dungan K M, Weitgasser R, Perez Manghi F, Pintilei E, Fahrbach J L, Jiang H H, Shell J, Robertson K E
Division of Endocrinology, Diabetes and Metabolism, Ohio State University, Columbus, OH, USA.
Department of Internal Medicine, Wehrle-Diakonissen Hospital, Salzburg, Austria.
Diabetes Obes Metab. 2016 May;18(5):475-82. doi: 10.1111/dom.12634. Epub 2016 Feb 19.
To evaluate the safety and efficacy of once-weekly dulaglutide 1.5 mg, a long-acting glucagon-like peptide-1 receptor agonist, compared with placebo in patients with type 2 diabetes (T2D) on glimepiride monotherapy.
This phase III, randomized (4 : 1; dulaglutide:placebo), double-blind, placebo-controlled, 24-week study compared the safety and efficacy of once-weekly dulaglutide 1.5 mg with placebo in sulphonylurea-treated (≥half-maximal dose, stable ≥3 months) patients (N = 300) with T2D and inadequate glycaemic control [glycated haemoglobin (HbA1c) ≥7.5 and ≤9.5% (≥58 mmol/mol and ≤80 mmol/mol)]. Analysis was carried out according to intention-to-treat.
At baseline, the mean participant age was 58 years; mean HbA1c was 8.4% (68 mmol/mol) and mean weight was 85.5 kg. Dulaglutide 1.5 mg was superior to placebo at 24 weeks for HbA1c reduction from baseline with a between-group HbA1c difference of -1.3% [95% confidence interval (CI) -1.6, -1.0] or -14 mmol/mol (95% CI -17, -11); p < 0.001. A greater proportion of participants in the dulaglutide group reached an HbA1c level of <7.0% (53 mmol/mol) compared with placebo (55.3% vs 18.9%; p < 0.001). Dulaglutide significantly decreased fasting serum glucose from baseline compared with placebo (between-group difference -1.86 mmol/l (95% CI -2.58, -1.14) or -33.54 mg/dl (95% CI -46.55, -20.53); p < 0.001. Weight was decreased significantly from baseline in the dulaglutide group (p < 0.001); the between-group difference was not significant. The most common treatment-emergent adverse events for dulaglutide 1.5 mg were gastrointestinal: nausea (10.5%), diarrhoea (8.4%) and eructation (5.9%). Total hypoglycaemia was higher with dulaglutide 1.5 mg vs placebo (2.37 and 0.07 events/participant/year, respectively; p = 0.025). No severe hypoglycaemia was reported.
Once-weekly dulaglutide 1.5 mg had a favourable benefit/risk profile when added to glimepiride monotherapy.
评估每周一次注射1.5毫克度拉糖肽（一种长效胰高血糖素样肽-1受体激动剂）与安慰剂相比，在接受格列美脲单药治疗的2型糖尿病（T2D）患者中的安全性和有效性。
这项III期随机（4∶1；度拉糖肽∶安慰剂）、双盲、安慰剂对照、为期24周的研究，比较了每周一次注射1.5毫克度拉糖肽与安慰剂在接受磺脲类药物治疗（≥最大剂量的一半，稳定≥3个月）、糖化血红蛋白（HbA1c）≥7.5%且≤9.5%（≥58 mmol/mol且≤80 mmol/mol）、血糖控制不佳的T2D患者（N = 300）中的安全性和有效性。分析采用意向性分析。
基线时，参与者的平均年龄为58岁；平均HbA1c为8.4%（68 mmol/mol），平均体重为85.5千克。在24周时，度拉糖肽1.5毫克组在降低HbA1c方面优于安慰剂组，组间HbA1c差异为-1.3%[95%置信区间（CI）-1.6，-1.0]或-14 mmol/mol（95% CI -17，-11）；p < 0.001。与安慰剂组相比，度拉糖肽组达到HbA < 7.0%（53 mmol/mol）水平的参与者比例更高（55.3%对18.9%；p < 0.001）。与安慰剂相比，度拉糖肽显著降低了空腹血清葡萄糖水平（组间差异为-1.86 mmol/L（95% CI -2.58，-1.14）或-33.54 mg/dL（95% CI -46.55，-20.53）；p < 0.001）。度拉糖肽组的体重较基线显著下降（p < 0.001）；组间差异不显著。度拉糖肽1.5毫克最常见的治疗中出现的不良事件为胃肠道反应：恶心（10.5%）、腹泻（8.4%）和嗳气（5.9%）。度拉糖肽1.5毫克组的总低血糖发生率高于安慰剂组（分别为2.37和0.07次事件/参与者/年；p = 0.025）。未报告严重低血糖事件。
在格列美脲单药治疗基础上加用每周一次注射1.5毫克度拉糖肽具有良好的效益/风险比。
