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A review of exenatide as adjunctive therapy in patients with type 2 diabetes

机译：艾塞那肽作为2型糖尿病患者辅助治疗的综述

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Background: Incretin glucagon-like peptide-1 (GLP-1) is a hormone released from cells in the gastrointestinal tract (GI), leading to glucose-dependent insulin release from the pancreas. It also suppresses postprandial hyperglycemia, glucagon secretion and slows gastric emptying. Exenatide (EXE), a functional analog of human GLP-1, was approved by the US FDA in April 2005.Objective: This article reviews current primary literature on the clinical efficacy and safety of EXE in the treatment of type 2 diabetes mellitus (DM) and describes the pharmacokinetics, pharmacodynamics, dosing and administration of EXE.Methods: English-language articles were identified through a search of MEDLINE (1966 to March 2009), International Pharmaceutical Abstracts (1970 to present), and Cochrane Database of Systemic Reviews (1995 to March 2009). Search terms included EXE, diabetes mellitus, postprandial hyperglycemia, gastric emptying, glucagon, pharmacokinetics and pharmacodynamics. Articles were selected for review if their designs were randomized, blinded and of controlled design that focused on clinical outcomes of patients with type 2 DM.Results: EXE is administered subcutaneously in the thigh, abdomen or upper arm within the 60-minute period before the morning and evening meals. Its Cmax is reached within 2.1 hours, and its T1/2 in 2.4 hours. EXE’s metabolism is primarily through the kidneys. For the patients who received EXE 10 μg SC BID in three, 30-week, placebo-controlled studies with background sulfonylureas (SUs), metformin (MET), or SU + MET, there were significant reductions in HbA1c (0.77 to 0.86%), fasting plasma glucose (0.6 mmol/L) and body weight (1.6 to 2.8 kg) (P ≤ 0.05 vs PCB) that were sustained in patients who completed two open-label phase trials with an additional 52 weeks of therapy. The use of thiazolidinediones was associated with a slight advantage over EXE in improving HbA1c along with increased weight gain; those who received EXE lost weight, but experienced more GI adverse effects. Patients who received EXE lost significant body weight while patients who received insulin gained weight. Patients receiving insulin had lower fasting, prelunch and predinner glucose excursions while patients in the EXE groups had lower postprandial glucose levels. Nausea was most frequently (>20%) reported in patients receiving the highest dose of EXE (10 μg SC BID vs 5 μg SC BID).Conclusions: EXE at the dose of 10 μg SC BID has been proven to decrease HbAlc by 1.3% ± 0.1% and decrease body weight by up to 5.3 ± 0.8 kg at week 82. Nausea was the most frequently reported adverse event (>20%) especially in patients being treated with EXE 10 μg SC BID. EXE can be safely added to MET therapy, SU therapy or MET + SU combination to effectively target glycemic goals in patients with type 2 DM. Long-term, head-to-head studies assessing the effect of the EXE ± oral agents/insulins in patients with HbAlc ≥ 10% are still needed to fully clarify the role of EXE in poorly controlled patients with type 2 DM.
机译：背景：肠抑素胰高血糖素样肽1（GLP-1）是一种从胃肠道（GI）细胞释放的激素，可导致胰岛葡萄糖依赖性胰岛素释放。它还可以抑制餐后高血糖，胰高血糖素分泌并减缓胃排空。 Exenatide（EXE）是人类GLP-1的功能类似物，已于2005年4月获得美国FDA批准。目的：本文综述了有关EXE在2型糖尿病（DM）治疗中的临床疗效和安全性的主要文献。方法）：通过检索MEDLINE（1966年至2009年3月），International Pharmaceutical Abstracts（1970年至今）和Cochrane Systemic Reviews数据库（系统检索，英文文献）来识别EXE的药代动力学，药效学，剂量和用法。 1995年至2009年3月）。搜索词包括EXE，糖尿病，餐后高血糖，胃排空，胰高血糖素，药代动力学和药效学。如果研究的设计是针对2型DM患者的临床结果的随机，盲法和对照设计，则选择这些文章进行审查。结果：EXE植入前60分钟内在大腿，腹部或上臂皮下注射早晚餐。其Cmax在2.1小时内达到，而T1 / 2在2.4小时内达到。 EXE的新陈代谢主要是通过肾脏。对于使用背景磺酰脲类药物（SUs），二甲双胍（MET）或SU + MET进行的三，30周，安慰剂对照研究，接受EXE 10μgSC BID治疗的患者，HbA1c显着降低（0.77至0.86％） ，空腹血糖（0.6 mmol / L）和体重（1.6至2.8 kg）（与PCB相比P≤0.05），这些患者在完成两项开放性试验并进行了另外52周的治疗后均得到了维持。噻唑烷二酮的使用与EXE相比在改善HbA1c和增加体重方面略有优势。那些接受EXE减肥的人，但经历了更多的胃肠道不良反应。接受EXE治疗的患者体重明显减轻，而接受胰岛素治疗的患者体重增加。接受胰岛素治疗的患者的空腹，餐前和餐前血糖波动较低，而EXE组的患者餐后血糖水平较低。在接受最高剂量EXE（10μgSC BID与5μgSC BID）的患者中，最经常报告恶心（> 20％）。结论：事实证明，以10μgSC BID的剂量EXE可使HbAlc降低1.3％在第82周时，±0.1％的体重减轻了5.3±0.8 kg的重量。恶心是最常报告的不良事件（> 20％），尤其是在接受EXE 10μgSC BID治疗的患者中。 EXE可以安全地添加到MET治疗，SU治疗或MET + SU组合中，以有效地靶向2型DM患者的血糖目标。仍需要进行长期的，头对头的评估，以评估EXE±口服药物/胰岛素对HbAlc≥10％的患者的作用，以充分阐明EXE在2型DM控制不佳的患者中的作用。

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