西格列汀.ppt

糖尿病口服药治疗进展——GLP-1类似物和DPP-IV抑制剂 北京大学第一医院内分泌科 姚军 2012-4-25 肠促胰素 (Incretins ) 是肠道内分泌细胞摄食后反应性分泌的激素，参与血糖的正常调节 GLP-1 和 GIP 是两种最主要的 incretins GLP-1（ glucagon-like peptide-1） GIP（glucose-dependent insulinoptropic polypeptide） Incretins 通过多种作用影响葡萄糖的动态平衡 有关艾噻那肽和西格列汀的研究 基于肠促胰泌素治疗的降糖和CVD危险替代标志物的研究 艾噻那肽与西格列汀作用比较 艾噻那肽与西格列汀作用比较 如何正确选择目标患者 DPPIV抑制剂 特点：口服，相对降糖活性弱，体重中性，对胃排空影响小 适应症 相对处于疾病早期 老年人 相对肥胖度不高者 可使用口服药联合者特别是二甲双胍 如何正确选择目标患者 GLP-1受体激动剂 特点：相对降糖活性强，减重效好，对胃排空影响明显 适应症 相对处于疾病早期 肥胖度较高者 食欲亢进，控制饮食困难者 可使用口服药联合者特别是二甲双胍 能接受皮下注射者 禁忌症 明确诊断的胃肠道疾患特别是胃排空障碍者 急性胰腺炎或其高危人群 * Single doses of 西格列汀25 mg and 200 mg resulted in rapid and marked inhibition of plasma DPP-4 activity.1 Throughout the 12-hour post-dose period, the 200 mg dose was associated 和 approximately 95% plasma DPP-4 inhibition, falling to approximately 80% inhibition at 24 hours post dose. The 25 mg dose was associated 和 peak inhibition of approximately 85%, falling to approximately 50% inhibition at 24 hours post dose.1 Reference Data on file, MSD ______________________. * Mean Values in HbA1c The graph shows that treatment with sitagliptin 100 mg/day resulted in a significant decrease in HbA1c, which was maintained throughout the period of the study.* Conversely, a gradual continuing increase was seen in the placebo group.1 R.1/Raz,p2569-F.1a R.1/Raz, p2566-Par.2-L1-5p2566-Par.5-L1p2567-T.1 R.1/Aschner, p2634-F.1A R.1/Aschner, p2634-T.1 R.1/Aschner, p2633-Par.9-L1-6 R.1/Aschner, p2634-Par.1-L1 R.1/Nonaka Poster F.3 F.4 * * HL Refs DeFronzo_Curr_Med_Res_Opin_2008_p7,8,13,17,25,31_ms.doc Amylin_BCA403_SDS_2.9.1.1_2.9.3_p107,108,109,116.pdf DISCUSSION1 Exenatide treatment reduced the rate of gastric emptying compared with rates at baseline and with sitagliptin treatment Exenatide decreased acetaminophen AUC0-240 min (mg ? min/dL) by 44% vs sitagliptin (0.56 ± 0.05; geometric LS mean ratio ± SE; P0.0001)2 Sitagliptin had no effect on gastric emptying BACKGROUND1 This was a Phase 4, double-blind, randomized, double-d