Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.
Diabet Med. 2012 Dec;29(12):1515-23. doi: 10.1111/j.1464-5491.2012.03699.x.
To quantify how much exenatide added to metformin improves β-cell function, and to evaluate the impact on glycaemic control, insulin resistance and inflammation compared with metformin alone.
A total of 174 patients with Type 2 diabetes with poor glycaemic control were instructed to take metformin for 8 ± 2 months, then they were randomly assigned to exenatide (5 μg twice a day for the first 4 weeks and forced titration to 10 μg twice a day thereafter) or placebo for 12 months. At 12 months we evaluated anthropometric measurements, glycaemic control, insulin resistance and β-cell function variables, glucagon, adiponectin, high sensitivity-C reactive protein and tumour necrosis factor-α. Before and after 12 months, patients underwent a combined euglycaemic hyperinsulinaemic and hyperglycaemic clamp, with subsequent arginine stimulation.
Exenatide + metformin gave a greater decrease in body weight, glycaemic control, fasting plasma proinsulin and insulin and their ratio, homeostasis model assessment for insulin resistance (HOMA-IR), and glucagon values and a greater increase in C-peptide levels, homeostasis model assessment β-cell function index (HOMA-β) and adiponectin compared with placebo + metformin. Exenatide + metformin decreased waist and hip circumference, and reduced concentrations of high sensitivity-C reactive protein and tumour necrosis factor-α. Exenatide + metformin gave a greater increase in M value (+34%), and disposition index (+55%) compared with placebo + metformin; first (+21%) and second phase (+34%) C-peptide response to glucose and C-peptide response to arginine (+25%) were also improved by exenatide + metformin treatment, but not by placebo + metformin.
Exenatide is effective not only on glycaemic control, but also in protecting β-cells and in reducing inflammation.
定量评估在二甲双胍的基础上加用艾塞那肽对β细胞功能的改善作用，并评价其对血糖控制、胰岛素抵抗和炎症的影响与二甲双胍单药治疗的差异。
共纳入 174 例血糖控制不佳的 2 型糖尿病患者，予二甲双胍治疗 8±2 个月，随后随机分为艾塞那肽（5μg，每日 2 次，持续 4 周，随后剂量增至 10μg，每日 2 次）或安慰剂组，治疗 12 个月。12 个月时评估患者的人体测量学指标、血糖控制、胰岛素抵抗和β细胞功能相关变量、胰高血糖素、脂联素、高敏 C 反应蛋白和肿瘤坏死因子-α。治疗前后行联合的正常血糖高胰岛素及高血糖钳夹试验，并随后进行精氨酸刺激试验。
与安慰剂+二甲双胍相比，艾塞那肽+二甲双胍治疗可使体重、血糖控制、空腹胰岛素原和胰岛素及其比值、稳态模型评估的胰岛素抵抗（HOMA-IR）、胰高血糖素水平以及 C 肽水平、稳态模型评估β细胞功能指数（HOMA-β）和脂联素水平显著下降，而腰围和臀围、高敏 C 反应蛋白和肿瘤坏死因子-α浓度显著降低。艾塞那肽+二甲双胍可使葡萄糖刺激的 M 值（+34%）和葡萄糖刺激的胰岛素分泌指数（+55%）显著增加，且第一时相（+21%）和第二时相（+34%）C 肽对葡萄糖的反应以及 C 肽对精氨酸的反应（+25%）均显著改善，而安慰剂+二甲双胍则无此作用。
艾塞那肽不仅能有效控制血糖，还能保护β细胞并减轻炎症。
