Amylin Pharmaceuticals, LLC, San Diego, CA 92121, USA.
Postgrad Med. 2013 May;125(3):47-57. doi: 10.3810/pgm.2013.05.2660.
Exenatide is a glucagon-like peptide-1 receptor agonist demonstrated to improve glycemic control with low hypoglycemia risk in patients with type 2 diabetes mellitus. The Diabetes Therapy Utilization: Researching Changes in A1C, Weight, and Other Factors Through Intervention With Exenatide Once Weekly (DURATION) program comprised 6 randomized, comparator-controlled, 24- to 30-week trials of exenatide once weekly (EQW), an extended-release formulation. This post hoc analysis pooled data from patients taking EQW across 6 trials to assess efficacy and safety in a large, varied patient population.
The intent-to-treat (ITT) population contained 1379 patients (baseline mean ± standard deviation glycated hemoglobin [HbA1c] levels of 8.4% ± 1.1%) who were treated with EQW over the course of 24 to 30 weeks. Changes from baseline in efficacy parameters for the ITT population and a completer population (1195 patients with ≥ 22 weeks of exposure) were evaluated.
The ITT population experienced significant reductions from baseline (least-squares mean [95% CI]) in HbA1c levels (-1.4% [-1.5% to -1.4%]), fasting blood glucose levels (-36 mg/dL [-38.4 mg/dL to -33.8 mg/dL]), and body weight (-2.5 kg [-2.8 kg to -2.3 kg]) after 24 to 30 weeks of EQW treatment. Reductions in HbA1c and fasting blood glucose levels were observed across baseline HbA1c level strata; patients with higher baseline HbA1c levels experienced greater reductions. Treatment with EQW was associated with modest, significant reductions in blood pressure (systolic blood pressure, -2.8 mm Hg [-3.5 mm Hg to -2.1 mm Hg]; diastolic blood pressure, -0.8 mm Hg [-1.2 mm Hg to -0.4 mm Hg]), and fasting lipid levels (total cholesterol, -6.5 mg/dL [-8.2 mg/dL to -4.7 mg/dL]; low-density lipoprotein cholesterol, -3.9 mg/dL [5.3 mg/dL to -2.5 mg/dL]; and triglyceride [geometric least-squares mean percent change (95% CI)], -6% [-8% to -4%] levels). Similar reductions were observed in the completer population. Exenatide once weekly was generally well tolerated. Transient, mild-to-moderate gastrointestinal treatment-emergent adverse events and injection-site treatment-emergent adverse events were reported most frequently, but were seldom treatment limiting. No major hypoglycemic events were observed; minor hypoglycemic events occurred infrequently in patients not using a sulfonylurea.
This post hoc analysis of > 1300 patients demonstrated that EQW was associated with significant reductions in HbA1c levels, body weight, blood pressure, and fasting lipid levels, with minimal hypoglycemia risk. Consistent with established safety profiles, EQW therapy was generally well tolerated.
www.ClinicalTrials.gov identifiers: NCT00308139, NCT00637273, NCT00641056, NCT00676338, NCT00877890, NCT01029886.
Exenatide 是一种胰高血糖素样肽-1 受体激动剂，已被证明可改善 2 型糖尿病患者的血糖控制，同时低血糖风险低。糖尿病治疗利用：通过每周一次给予 Exenatide 进行干预研究 A1C、体重和其他因素的变化（DURATION）计划包括 6 项随机、对照、24 至 30 周的 Exenatide 每周一次（EQW）、延长释放制剂的试验。这项事后分析汇总了来自 6 项试验中接受 EQW 治疗的患者的数据，以评估在大量、多样化的患者群体中该药物的疗效和安全性。
意向治疗（ITT）人群包含 1379 名患者（基线平均±标准偏差糖化血红蛋白[HbA1c]水平为 8.4%±1.1%），他们在 24 至 30 周的时间内接受 EQW 治疗。评估了 ITT 人群和完成者人群（1195 名暴露时间≥22 周的患者）的疗效参数的变化。
ITT 人群在接受 EQW 治疗 24 至 30 周后，HbA1c 水平（最小二乘均值[95%CI]）显著降低（-1.4%[-1.5%至-1.4%]），空腹血糖水平（-36mg/dL[-38.4mg/dL 至-33.8mg/dL]）和体重（-2.5kg[-2.8kg 至-2.3kg]）。HbA1c 水平的基线水平分层中观察到 HbA1c 和空腹血糖水平的降低；基线 HbA1c 水平较高的患者降幅更大。接受 EQW 治疗与血压（收缩压，-2.8mmHg[-3.5mmHg 至-2.1mmHg]；舒张压，-0.8mmHg[-1.2mmHg 至-0.4mmHg]）和空腹血脂水平（总胆固醇，-6.5mg/dL[-8.2mg/dL 至-4.7mg/dL]；低密度脂蛋白胆固醇，-3.9mg/dL[5.3mg/dL 至-2.5mg/dL]；和甘油三酯[几何最小二乘均值百分比变化（95%CI）]，-6%[-8%至-4%]）的适度、显著降低相关。在完成者人群中也观察到类似的降低。每周一次给予 Exenatide 通常耐受性良好。最常报告的是短暂的、轻度至中度胃肠道治疗出现的不良反应和注射部位治疗出现的不良反应，但很少有治疗限制。未观察到严重的低血糖事件；未使用磺酰脲类药物的患者低血糖事件发生频率较低。
这项对超过 1300 名患者的事后分析表明，EQW 与 HbA1c 水平、体重、血压和空腹血脂水平的显著降低相关，低血糖风险最小。与既定的安全性特征一致，EQW 治疗通常耐受性良好。
www.ClinicalTrials.gov 标识符：NCT00308139、NCT00637273、NCT00641056、NCT00676338、NCT00877890、NCT01029886。
