Amylin Pharmaceuticals, Inc. San Diego, CA, USA.
Diabetes Metab Syndr Obes. 2012;5:29-41. doi: 10.2147/DMSO.S28387. Epub 2012 Feb 20.
Exenatide twice daily is a first-in-class glucagon-like peptide receptor agonist approved for the treatment of type 2 diabetes. The objective of this analysis was to evaluate the safety profile of exenatide twice daily and to compare its profile with that of a pooled comparator (placebo and insulin) in patients with type 2 diabetes.
Data from 19 completed, randomized, controlled clinical trials of exenatide twice daily (5 μg and 10 μg) were pooled and analyzed; the pooled data included 5594 intent-to-treat patients who were followed for 12-52 weeks. Incidence rates, exposure-adjusted incidence rates, and 95% confidence intervals around risk differences between groups were calculated.
Baseline demographics and exposure time were comparable between groups (exenatide, N = 3261; pooled comparator, N = 2333; mean exposure time 166-171 days). Transient, mild- to-moderate nausea was the most frequent adverse event with exenatide (36.9% versus 8.3% in the pooled comparator). The incidence of hypoglycemia (minor or major) with concomitant sulfonylurea (exenatide 26.5%, pooled comparator 20.7%) was higher than that without sulfonylurea (exenatide 3.1%, pooled comparator 2.7%) in all groups. Serious adverse events, discontinuations due to serious adverse events, and deaths were reported with similar frequency in the exenatide and pooled comparator groups. Composite exposure-adjusted incidence rates were not statistically different between groups for pancreatitis, renal impairment, or major adverse cardiac events; there was a difference in incidence rates for benign thyroid neoplasm (0.3% versus 0%).
Overall, this analysis, representing over 1500 patient-years of exposure, demonstrated that exenatide twice daily was safe and generally well tolerated in patients with type 2 diabetes. The incidence of most adverse events, including serious adverse events, was similar in both exenatide-treated and comparator-treated patients. The most distinct differences between groups were in gastrointestinal-related adverse events, which is consistent with other therapies within the glucagon-like peptide class.
每日两次给予艾塞那肽是一种新型胰高血糖素样肽受体激动剂，适用于治疗 2 型糖尿病。本分析的目的是评估每日两次给予艾塞那肽的安全性概况，并与 2 型糖尿病患者中汇集的对照药物（安慰剂和胰岛素）的安全性概况进行比较。
对每日两次给予艾塞那肽（5μg 和 10μg）的 19 项已完成的随机对照临床试验的数据进行了汇总和分析；汇总数据包括 5594 例意向治疗患者，随访 12-52 周。计算了组间发生率、暴露调整发生率和风险差异的 95%置信区间。
组间的基线人口统计学和暴露时间相似（艾塞那肽组，N=3261；汇集的对照药物组，N=2333；平均暴露时间 166-171 天）。短暂的、轻度至中度的恶心是艾塞那肽最常见的不良反应（36.9%对比汇集的对照药物组的 8.3%）。与磺酰脲类药物合用（艾塞那肽 26.5%，汇集的对照药物组 20.7%）时，低血糖（轻度或重度）的发生率高于不与磺酰脲类药物合用（艾塞那肽 3.1%，汇集的对照药物组 2.7%）。在所有组中，均有严重不良事件、因严重不良事件停药和死亡的报告，且两组的报告频率相似。胰腺炎、肾功能损害或主要不良心脏事件的复合暴露调整发生率在艾塞那肽组和汇集的对照药物组之间无统计学差异；甲状腺良性肿瘤的发生率存在差异（0.3%对比 0%）。
总体而言，这项分析代表了超过 1500 患者-年的暴露，表明每日两次给予艾塞那肽在 2 型糖尿病患者中是安全的，通常可耐受。大多数不良事件的发生率，包括严重不良事件，在艾塞那肽治疗和对照药物治疗的患者中相似。组间最明显的差异是胃肠道相关的不良事件，这与其他胰高血糖素样肽类药物一致。
