基于肠促胰岛素的2型糖尿病治疗新模式

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Confidential,for internal planning purposes only.Not to be shared or distributed outside of the BMS/AZ saxagliptin/dapagliflozin collaborative teams.,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Confidential,for internal planning purposes only.Not to be shared or distributed outside of the BMS/AZ saxagliptin/dapagliflozin collaborative teams.,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Confidential,for internal planning purposes only.Not to be shared or distributed outside of the BMS/AZ saxagliptin/dapagliflozin collaborative teams.,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Confidential,for internal planning purposes only.Not to be shared or distributed outside of the BMS/AZ saxagliptin/dapagliflozin collaborative teams.,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Confidential,for internal planning purposes only.Not to be shared ordistributed outside of the BMS/AZ saxagliptin/dapagliflozin collaborative teams.,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Confidential,for internal planning purposes only.Not to be shared ordistributed outside of the BMS/AZ saxagliptin/dapagliflozin collaborative teams.,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Confidential,for internal planning purposes only.Not to be shared or distributed outside of the BMS/AZ saxagliptin/dapagliflozin collaborative teams.,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Confidential,for internal planning purposes only.Not to be shared ordistributed outside of the BMS/AZ saxagliptin/dapagliflozin collaborative teams.,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Confidential,for internal planning purposes only.Not to be shared or distributed outside of the BMS/AZ saxagliptin/dapagliflozin collaborative teams.,Fare clic per modificare gli stili del testo dello schema,Secondo livello,Terzo livello,Quarto livello,Quinto livello,Fare clic per modificare stile,Fare clic per modificare gli stili del testo dello schema,Secondo livello,Terzo livello,Quarto livello,Quinto livello,Fare clic per modificare stile,DRAFT,百时美施贵宝,/,阿斯利康机密文件,-,仅供内部人员使用,Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,基于肠促胰岛素的,2,型糖尿病,治疗新模式,内容介绍,糖尿病的发生及治疗现状,DPP-4,抑制剂,安立泽,（沙格列汀片,5mg,）,疗效,安全性,用法用量,1,2,2,型糖尿病的发生与多个组织器官密切相关,肝糖输出增加,脂解作用增强,高血糖症,葡萄糖摄取减少,肌肉,肝脏,脂肪组织,胰腺,胰岛素分泌减少,胰高血糖素分泌增加,肠促胰素作用降低,2,型糖尿病患者病理基础：胰腺、肌肉、肝脏、脂肪组织及肠促胰岛素系统等多个生理系统的功能出现异常,2,型糖尿病的治疗现状,作用靶点,副作用,胰岛素,分泌不足,胰岛素抵抗,体重增加,低血糖症,胃肠道,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,!,DPP-4,抑制剂,GLP-1,受体激动剂,!,70%,的患者血糖控制未达标,目前,2,型糖尿病的治疗药物主要分为,6,大类，各药物在作用机制、疗效、安全性和耐受性等方面的情况也各不相同,1.Nathan DM,et al.Diabetologia.2009;52:17-30.2.,Stumvoll M,et al.Lancet.2005;365:1333-46.,不同,降糖,药物的作用靶点及副作用,1,2,内容介绍,糖尿病的发生及治疗现状,DPP-4,抑制剂,安立泽,（沙格列汀片,5mg,）,疗效,安全性,用法用量,1,2,H,2,N,N,O,CN,HO,沙格列汀,1.Augeri DJ,et al.J Med Chem.2005;48:5025-37.2.Kirby M,et al.Clin Sci(Lond).2009;118:31-41.3.,Boulton DW.Diabetes.2007;56(Suppl.1):A161.,安立泽,（,沙格列汀5,mg,）,高效的,DPP-4,抑制剂,为,DPP-4,的高选择性、可逆、具有口服活性的竞争性抑制剂,口服,用药,后迅速、广泛吸收,沙格列汀,的代谢主要由,CYP3A4/5,介导，主要代谢产物也是,DPP4,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,5mg,剂量的药效学,特,性支持每日一次给药,作用时间长达,24,小时,安立泽,双重机制,作用于,、,细胞,安立泽具有双重作用机制，可作用于胰腺,、,细胞，调节血糖浓度,安立泽血糖依赖性降糖，降低血糖的同时有效减少低血糖的发生,血糖浓度高时,高效抑制,DPP,4,酶，生理性,GLP,1,浓度增加,葡萄糖输出减少,单药治疗：显著改善糖尿病患者三个关键指标,安立泽,疗效：全面有效降低糖尿病患者血糖水平,安立泽,5mg,治疗,6,个月,HbA,1c,的平均改变,安立泽,5mg,治疗,6,个月的,平均改变（,mg/dL,）,0,-0.1,-0.2,-0.3,-0.4,-0.5,-0.6,-0.7,-0.8,-0.7%,-15,-37,0,-10,-20,-30,-40,HbA,1C,FPG,2,小时,PPG,基线,HbA,1c,8.0%,Rosenstocka J,Aguilar-Salinasb C,Kleinc E,et al.Effect of saxagliptin monotherapy in treatment-nave patients with type 2 diabetes.CURRENT MEDICAL RESEARCH AND OPINION.2009;25(10):24012411.,安立泽单药治疗,24,周，有效降低患者,FPG,、,PPG,和,HbA,1c,水平,N=105,联合二甲双胍治疗：全面有效降低血糖水平，重获血糖控制,安立泽,5mg,联合二甲双胍治疗,6,个月,HbA,1c,的平均改变,安立泽,5mg,联合二甲双胍治疗,6,个月平均改变（,mg/dL,）,0,-0.1,-0.2,-0.3,-0.4,-0.5,-0.6,-0.7,-0.8,-0.83%,-23.3,-41.1,0,-10,-20,-30,-40,-50,HbA,1C,FPG,2,小时,PPG,DEFRONZO RA,DUAN RY,HISSA MN,et al.The Efficacy and Safety of Saxagliptin When Added to Metformin Therapy in Patients With Inadequately Controlled Type 2 Diabetes With Metformin Alone.Diabetes Care.2009;32:16491655.,在使用二甲双胍单药治疗血糖控制不佳的患者中，安立泽联合二甲双胍治疗,24,周可有效降低患者,FPG,、,PPG,和,HbA,1c,水平,安立泽,疗效：全面有效降低糖尿病患者血糖水平,基线,HbA,1c,8.1%,N=191,周,HbA,1C,(%),较基线平均改变,(SE),BL,4,8,12,16,20,30,37,50,63,76,89,102,6,24,沙格列汀