Yoo Bong Kyu, Triller Darren Michael, Yoo Dong Joo
Department of Pharmacy Practice, College of Pharmacy, Yeungnam University, Kyungsan, Kyungbuk, Korea.
Ann Pharmacother. 2006 Oct;40(10):1777-84. doi: 10.1345/aph.1H060. Epub 2006 Sep 19.
To evaluate available literature characterizing the pharmacology, pharmacokinetics, drug interactions, efficacy, and safety of exenatide in patients with type 2 diabetes.
A PubMed database search (1966-May 2006) was conducted, using exenatide as the search term. The manufacturer's prescribing information was also used.
English-language articles were selected and data were extracted with a focus on clinical outcomes associated with the treatment of patients with type 2 diabetes.
Exenatide exerts a glucoregulatory effect by various mechanisms including secretion of glucose-dependent insulin, suppression of inappropriately high glucagon levels in patients with type 2 diabetes, delayed gastric emptying, and reduction of food intake. In placebo-controlled clinical studies, plasma exenatide concentrations appeared to exhibit dose-proportional kinetics, reaching peak plasma levels between 2 and 3 hours after a single subcutaneous injection. Exenatide's elimination half-life ranged from 3.3 to 4.0 hours, and the time to reach maximum concentration was about 2 hours. Interactions between exenatide and agents such as digoxin and lisinopril were not considered significant. In Phase III trials, exenatide demonstrated significant reduction of hemoglobin A1c levels from baseline and compared with placebo after 30 weeks of treatment in patients unable to achieve optimal glycemic control with metformin, a sulfonylurea, or oral combination therapy (0.4-0.9%). Patients' weight decreased with exenatide (0.9-2.8 kg), but adverse gastrointestinal (GI) events were common. Exenatide combined with thiazolidonediones, D-phenylalanine derivatives, meglitinides, or alpha glucosidase inhibitors has not been studied.
Clinical trials have demonstrated that exenatide improves glycemic control when added to sulfonylureas and metformin, and it may be an alternative to insulin glargine in patients requiring additional therapy. Hypoglycemia has been encountered in clinical trials of exenatide, especially upon initiation of therapy with sulfonylureas (not with metformin); close patient monitoring is therefore recommended. Further studies should assess the impact of exenatide on clinical outcomes such as micro- and macrovascular disease.
评估现有文献中关于艾塞那肽在2型糖尿病患者中的药理学、药代动力学、药物相互作用、疗效及安全性。
利用艾塞那肽作为检索词，检索了PubMed数据库（1966年至2006年5月）。还使用了药品制造商的处方信息。
选择英文文章并提取数据，重点关注与2型糖尿病患者治疗相关的临床结果。
艾塞那肽通过多种机制发挥血糖调节作用，包括分泌葡萄糖依赖性胰岛素、抑制2型糖尿病患者不适当的高胰高血糖素水平、延迟胃排空及减少食物摄入量。在安慰剂对照的临床研究中，单次皮下注射后，血浆艾塞那肽浓度似乎呈现剂量比例动力学，在2至3小时达到血浆峰值水平。艾塞那肽的消除半衰期为3.3至4.0小时，达到最大浓度的时间约为2小时。艾塞那肽与地高辛和赖诺普利等药物之间的相互作用不显著。在III期试验中，对于使用二甲双胍、磺脲类药物或口服联合治疗无法实现最佳血糖控制的患者，治疗30周后，与安慰剂相比，艾塞那肽使糖化血红蛋白水平从基线显著降低（0.4 - 0.9%）。使用艾塞那肽后患者体重下降（0.9 - 2.8千克），但胃肠道不良事件常见。尚未对艾塞那肽与噻唑烷二酮类、D - 苯丙氨酸衍生物、格列奈类或α - 葡萄糖苷酶抑制剂联合使用进行研究。
临床试验表明，在磺脲类药物和二甲双胍基础上加用艾塞那肽可改善血糖控制，对于需要额外治疗的患者，它可能是甘精胰岛素的替代药物。在艾塞那肽的临床试验中出现过低血糖，尤其是在开始使用磺脲类药物治疗时（二甲双胍治疗时未出现）；因此建议密切监测患者。进一步研究应评估艾塞那肽对微血管和大血管疾病等临床结局的影响。
