安立泽在2型糖尿病治疗中的作用课件

Click to edit Master text styles,Second level,Third level,Fourth level,*,Click to edit Master title style,CV-1202-ON-0156,有效期,:2013.2,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,CV-1202-ON-0156,有效期,:2013.2,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,*,*,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,*,*,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,*,*,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,*,*,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,*,*,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,*,*,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,*,*,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,*,*,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,*,*,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,*,*,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,*,*,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,*,*,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,*,*,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Click to edit Master title style,安立泽,在,2,型糖尿病治疗中的作用,安心降糖 立刻选择,安立泽 在2型糖尿病治疗中的作用,2,型糖尿病血糖控制达标率令人堪忧,摘自,2009,年全国糖尿病控制状况调查报告。中国医学会糖尿病分会,cdschina.org/xwzx.jsp.2019,64.72%,HbA1c7%,35.28%,达标,未达标,2009-2019,年全国糖尿病血糖控制状况调查：,中国近,65%,的,2,型糖尿病患者,HbA1c7.0%,2009,年,-2019,年，中华医学会糖尿病学分会进行的“,2,型糖尿病患者糖化血红蛋白控制状况调查”是大规模的糖尿病患者糖化血红蛋白控制状况抽样调查,7,HbA1c8,8,HbA1c9,HbA1c,9,25.42%,15.13%,24.17%,HbA1c,达标标准,:7.0%,2型糖尿病血糖控制达标率令人堪忧摘自2009年全国糖尿病控制,2,现有的方法不能满足所有的临床需求,Nathan DM,et al.Diabetologia.2009;52:17-30.,Stumvoll M,et al.Lancet.2019;365:1333-46.,Inzucchi SE.JAMA 2019;287(3):360-372.,Gallwitz B.Minerva Endocrinol.2019;31(2):133-147.,65%,的,2,型糖尿病患者血糖控制未达标,不同降糖药物的作用靶点及副作用,作用靶点,减少,肝糖输出,改善,胰岛素抵抗,增加,胰岛素分泌,体重,增加,低血,糖症,胃肠道,副作用,副作用,胰岛素,二甲双胍,磺脲类药物,格列奈类药物,-,葡萄糖苷酶抑制剂,噻唑烷二酮类药物,GLP-1,受体激动剂,DPP-4,抑制剂,现有的方法不能满足所有的临床需求Nathan DM,et a,3,DPP-4,抑制剂：,、,双重作用机制，葡萄糖依赖性降糖,Drucker DJ,Nauck MA.Lancet.2019;368:1696-705.,Idris,Donnelly R,Diabetes Obes Metab.2019;9:153-65.,Barnett A.Int J Clin Pract.2019;60:1454-70.,胃,胃肠道,肠,增加,并延长内源性,GLP-1,对,-,细胞的作用,葡萄糖依赖性胰岛素的分泌,净效应：血糖,增加,并延长内源性,GLP-1,和,GIP,对,-,细胞的作用,安立泽,胰高血糖素分泌,肠促胰素,细胞,胰腺,细胞,DPP-,4,*,进食,*,DPP-4,：,二肽基肽酶,-4,GLP-1,：,胰高血糖素样肽,-1,GIP,：,葡萄糖依赖性促胰岛素分泌多肽,DPP-4抑制剂：、双重作用机制，葡萄糖依赖性降糖Dru,4,在二甲双胍控制不佳的,2,型糖尿病患者中,加用,DPP-4,抑制剂与加用其他降糖药物的疗效相当,Mclntosh B,et al.Open Med.2019;5(1):e35-48,Epub 2019 Mar.,治疗,磺脲类,氯茴苯酸类,噻唑烷二酮类,DPP-4,抑制剂,-,糖苷酶抑制剂,GLP-1,类似物,MTC estinmate(95%Crl),-0.79(-0.95,-0.63),-0.64(-0.93,-0.37),-0.82(-1.00,-0.66),-0.80(-0.95,-0.65),-0.74(-0.98,-0.50),-0.82(-1.95,-0.59),治疗,更有效,安慰剂,更有效,-2.0,-1.0,-0.5,0,0.5,-1.5,A1C,自基线的改变,(%,95%CI),(,各治疗组之间比较无统计学差异,),基础胰岛素,双相胰岛素,-0.82(-1.16,-0.47),-0.97(-1.33,-0.61),在二甲双胍控制不佳的,2,型糖尿病患者加用,其他降糖药物降低,HbA1c,效果的,Meta,分析,在二甲双胍控制不佳的2型糖尿病患者中加用DPP-4抑制剂与,5,DPP-4,已经成为,AACE/ACE,糖尿病指南推荐一线用药之一,Rodbard HW,et al.Endocr Pract.2009;15:540-559.,DPP-4,DPP-4,DPP-4,DPP-4已经成为AACE/ACE糖尿病指南推荐一线用药之一,6,2019,年最新,ADA/EASD,指南推荐联用一线用药之一,2019年最新ADA/EASD指南推荐联用一线用药之一,7,安立泽,的药代动力学特性，,DPP-4,酶抑制力强,Augeri DJ,et al.J Med Chem.2019;48:5025-37,Kirby M,et al.Clin Sci(Lond).2009;118:31-41,Boulton DW.Diabetes.2019;56(Suppl.1):A161,高选择性的二肽基肽酶,4(DPP-4),竞争性抑制剂,5mg,每日一次口服给药，作用时间长达,24,小时,安立泽,与,DPP-4,酶共价键结合，抑制力强,中位达峰时间为,2,小时。可与食物同服或分开服用,其代谢主要由,CYP3A4/5,介导，主要代谢产物也是,DPP-4,抑制剂，其抑制活性作用是沙格列汀的二分之一,沙格列汀和,/,或代谢产物经由肾脏,(,主要途径,),和肝脏途径清除,安立泽的药代动力学特性，DPP-4酶抑制力强Augeri,8,单药治疗,与二甲双胍联合,(,二甲双胍单药控制不佳时,),单药治疗与二甲双胍联合(二甲双胍单药控制不佳时),9,沙格列汀升高胰岛素水平达,18.5%,沙格列汀单剂治疗升高胰岛素水平,Henry et al.Diabetes,Obesity and Metabolism 2019;13:850-858.,随机双盲、安慰剂平行对照研究，共,36,名健康志愿者分别服用沙格列汀,5mg qd(n=20),或安慰剂,(n=16),，观察胰岛素分泌量与胰高血糖素变化。,15.9,沙格列汀,5mg,(n=18),安慰剂,(n=15),-2.2,与基线对比的胰岛素水平变化,(%),30,20,10,0,-10,-20,沙格列汀升高胰岛素水平达18.5%沙格列汀单剂治疗升高胰岛素,10,沙格列汀单剂治疗降低胰高糖素水平,Henry et al.Diabetes,Obesity and Metabolism 2019;13:850-858.,随机双盲、安慰剂平行对照研究，共,36,名健康志愿者分别服用沙格列汀,5mg qd(n=20),或安慰剂,(n=16),，观察胰岛素分泌量与胰高血糖素变化。,沙格列汀单药治疗降低胰高糖素水平达,15.4%,-15.4,沙格列汀,5mg,(n=17),安慰剂,(n=14),8.2,自基线的改变,(%),30,20,10,0,-10,-20,P=0.03,沙格列汀单剂治疗降低胰高糖素水平Henry et al.D,11,单药治疗，安立泽,全面控制三大血糖关键指标,Rosenstock J,et al.Current Medical Research Opinion 2009;25(10):2401-2411,基线,HbA1c 8.0%,FPG,2,小时,PPG,HbA,1c,0,-0.1,-0.2,-0.3,-0.4,-0.5,-0.6,-0.7,