糖尿病药物罕治疗概述.ppt

谢谢！ * * 各种胰岛素的作用时间有所不同。 * GLP-1 相关的药物有两种治疗机制，一种是直接增加GLP-1的水平，即GLP-1受体激动剂；另一种是抑制DPP-4酶的活性，即DPP-4抑制剂；那么我们接下来看一下，基于这两种不同的治疗机制所产生的效果上的差异。 * identical experimental conditions Thomas L, Eckhardt M, Langkopf E, et al. (R)-8-(3-amino-piperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methylquinazolin-2-ylmethyl)-3,7-dihydro-purine-2,6-dione (BI 1356), a novel xanthine-based dipeptidyl peptidase 4 inhibitor, has a superior potency and longer duration of action compared with other dipeptidyl peptidase-4 inhibitors. J Pharmacol Exp Ther 2008; 325: 175-82 研究表明，维格列汀的肾脏清除率只占全部的三分之一（13 l/h:41 l/h）。虽然有85%由此排泄，但大部分是无活性的代谢产物。约23%的原药由肾排泄。这是其可以在肾损害人群中应用的基础。 1860研究是在LEAD项目（利拉鲁肽的全球大规模Ⅲ期临床研究）基础上进行的一项头对头比较利拉鲁肽与西格列汀疗效和安全性的研究。该研究在欧洲、美国及加拿大共纳入665例接受二甲双胍治疗（≥1500 mg/d，治疗持续时间≥3个月）血糖控制不佳（HbA1c为7.5%~10.0%，平均8.5%）的2型糖尿病患者，随机分配给予每日1次利拉鲁肽1.2 mg、1.8 mg或西格列汀100 mg治疗共26周。 * 研究结果显示，利拉鲁肽组患者HbA1c降幅显著高于西格列汀组（利拉鲁肽1.8 mg、1.2 mg与西格列汀组分别为-1.50%、-1.24%和-0.90%，利拉鲁肽与西格列汀组比较均为P0.0001 ） Figure 2 Effect of 1.2 mg liraglutide, 1.8 mg liraglutide or 100 mg sitagliptin on glycaemic control from baseline to 52 weeks. (A) Mean HbA1c values. Error bars are 1.96 SE, corresponding to the 95% CI. last observation carried forward：LOCF * During the core trial and extension 1, patients received either sitagliptin or liraglutide (1.2 mg or 1.8 mg); during extension 2, patients taking sitagliptin switched to either liraglutide 1.2 or 1. 8 mg. Here, by-week HbA1c measurements for the core trial period and first extension are shown for the entire population who later switched to liraglutide. On the next slide, this same population is shown as the two separate switch groups (patients who switched to liraglutide 1.2 mg , and patients who switched to liraglutide 1.8 mg). * Figure 3. Mean reductions in HbA1c by baseline category and proportions of participants reaching target endpoints with 1.2 mg liraglutide, 1.8 mg liraglutide and 100 mg sitagliptin from weeks 0–52 (B). Percentage of participants achieving target HbA1c 7% (ADA) or 6.