GLP糖尿病治疗的新希望.pptxVIP

GLP糖尿病治疗的新希望第1页/共27页 随着时间的延长，血糖控制逐渐恶化6.2% – upper limit of normal rangeMedian HbA1c (%)Conventional*GlibenclamideMetforminInsulinUKPDS6789Years from randomisatio58.56.5Recommended treatment target 7.0%?867.576.5Time (years)023451ADOPTMetforminGlibenclamideRosiglitazone*Diet initially then sulphonylureas, insulin and/or metformin if FPG15 mmol/L; ?ADA clinical practice recommendations. UKPDS 34, n=1704UKPDS 34. Lancet 1998:352:854–65; Kahn et al (ADOPT). NEJM 2006;355(23):2427–43第2页/共27页 体重增加Glibenclamide (n=277)Years from randomisationInsulin (n=409)Metformin (n=342) Conventional treatment (n=411); diet initially then sulphonylureas, insulin and/or metformin if FPG 15 mmol/LUKPDS: up to 8 kg in 12 yearsADOPT: up to 4.8 kg in 5 yearsWeight (kg) Rosiglitazone, 0.7 (0.6 to 0.8) Metformin, -0.3 (-0.4 to -0.2)** Glibenclamide, -0.2 (-0.3 to 0.0)**Change in weight (kg)015036912876432Years0123459692880100UKPDS 34. Lancet 1998:352:854–65. n=at baseline; Kahn et al (ADOPT). NEJM 2006;355(23):2427–43第3页/共27页 低血糖p0.05 glibenclamide vs. rosiglitazonePatients with hypoglycaemia** (%)1039051015202530354045RosiglitazoneMetforminGlibenclamide12Hypoglycaemia, events/patient/year*051020GlargineNPH*All symptomatic hypoglycaemic events15Riddle et al. Diabetes Care 2003;26:3080; Kahn et al (ADOPT). NEJM 2006;355:2427–43第4页/共27页 2型糖尿病的进展过程:HbA1c, FPG 和 PPG 恶化治疗加强伴随着体重增加及低血糖Beta细胞功能下降Incretin的治疗会改变这些状况吗？2型糖尿病的自然进展病史导致的结果是：逐步升级的治疗方法第5页/共27页 人体的GLP-1具有多重生理作用大脑 胰岛素分泌 (葡萄糖依赖)胰高血糖素分泌胰岛素合成?细胞量胰腺 肝脏 肝糖输出 能量摄取胃肠道减少动力 第6页/共27页 Slide No 7与人类GLP-1的氨基酸有97% 同源与人类GLP-1的氨基酸有53%同源Study duration: Liraglutide 26 weeks; exenatide 30 weeks.1LEAD1,2,3,4,5 meta-analysis of antibody formation; Data on file; 2DeFronzo et al. Diabetes Care 2005;28:1092 人类 GLP-1LiraglutideExenatideLiraglutide: 与人类GLP-1高度同源患者使用后抗体增加的比例 Liraglutide1 020406080100Exenatide + metformin243%8.6% liraglutide 抗体对疗效没有影响第7页/共27页 Butler et al. Diabetes 2003Meier et al. Diabetologia 20052型糖尿病β细胞凋亡增加第8页/共27页 Ritzel RA e