Comparison of safety and tolerability with continuous (exenatide once weekly) or intermittent (exenatide twice daily) GLP-1 receptor agonism in patients with type 2 diabetes
Comparison of safety and tolerability with continuous (exenatide once weekly) or intermittent (exenatide twice daily) GLP-1 receptor agonism in patients with type 2 diabetes
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DOI：
10.1111/j.1463-1326.2012.01639.x
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发表时间：
2012-12-01
影响因子：
5.8
通讯作者：
Porter, L.
中科院分区：
文献类型：
--
作者：
Ridge, T.;Moretto, T.;Porter, L.
目的：艾塞那肽是一种胰高血糖素样肽-1 受体激动剂，可改善 2 型糖尿病 (T2DM) 患者的血糖控制。每日两次制剂 (ExBID) 可实现间歇性艾塞那肽暴露，而每周一次制剂 (ExQW) 可提供连续艾塞那肽暴露。这项综合回顾性分析比较了 ExQW 与 ExBID 在 T2DM 患者中的安全性和耐受性。方法：数据来自两项直接比较 ExQW (N=277) 与 ExBID (N=268) 的开放标签、随机、对照对照试验。计算不良事件（AE）和低血糖发生率的组间差异。还总结了选定 AE（恶心、呕吐和注射部位相关 AE）随时间和持续时间的发生率。结果：最常见的 AE 是恶心、腹泻、注射部位瘙痒和呕吐。与 ExBID 相比，ExQW 组恶心和呕吐的发生频率较低，在开始治疗 (ExQW) 或开始治疗和剂量递增 (ExBID) 时达到峰值，并随着时间的推移而减少。很少有患者因胃肠道相关 AE 而停药。注射部位 AE 在 ExQW 中更为常见，但两组均随着时间的推移而减少。未发生严重低血糖；未同时使用磺脲类药物的患者发生轻微低血糖的发生率较低，ExQW 和 ExBID 之间没有差异。两组中报告的严重 AE 和因 AE 导致的停药频率相似。结论：两种艾塞那肽制剂总体上都是安全且耐受性良好的，ExQW 与恶心和呕吐较少相关，但注射部位 AE 较多。连续暴露与间歇暴露不会影响艾塞那肽的总体耐受性，没有证据表明连续暴露会导致不良事件持续时间延长或强度恶化。
Aims: Exenatide is a glucagon-like peptide-1 receptor agonist shown to improve glycaemic control in patients with type 2 diabetes (T2DM). Intermittent exenatide exposure is achieved with the twice-daily formulation (ExBID), while the once-weekly formulation (ExQW) provides continuous exenatide exposure. This integrated, retrospective analysis compared safety and tolerability of ExQW vs. ExBID in patients with T2DM.Methods: Data were pooled from two open-label, randomized, comparator-controlled, trials directly comparing ExQW (N=277) to ExBID (N=268). Between-group differences in adverse event (AE) and hypoglycaemia incidences were calculated. Incidence over time and duration of selected AEs (nausea, vomiting, and injection-site-related AEs) were also summarized.Results: The most common AEs were nausea, diarrhoea, injection-site pruritus, and vomiting. Nausea and vomiting occurred less frequently with ExQW vs. ExBID, peaking at initiation (ExQW) or at initiation and dose escalation (ExBID), and decreasing over time. Few patients discontinued because of gastrointestinal-related AEs. Injection-site AEs were more common with ExQW but decreased over time in both groups. No major hypoglycaemia occurred; minor hypoglycaemia occurred with low incidence in patients not using concomitant sulphonylurea, with no difference between ExQW and ExBID. Serious AEs and discontinuations because of AEs were reported with similar frequency in both groups.Conclusions: Both exenatide formulations were generally safe and well-tolerated, with ExQW associated with less nausea and vomiting but more injection-site AEs. Continuous vs. intermittent exposure did not impact the overall tolerability profile of exenatide, with no evidence of prolonged duration or worsened intensities of AEs with continuous exposure.