糖尿病药ppt课件

,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,#,单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,#,中国人群肥胖程度越高，糖尿病患病率越高,20,30, 18.5,18.5-24.9,25.0- 9.9,30,BMI (kg/m,2,),患病率,(%),糖尿病合计,糖尿病前期,4.5,11.2,7.6,13.1,12.8,19.9,18.5,26.7,Yang et al: N Engl J Med 2010;362:1090-1101,0,10,中国糖尿病和糖尿病前期患者的患病率与体重指数的关系,中国人群肥胖程度越高，糖尿病患病率越高2030 18.5,1,降低体重将对,2,型糖尿病患者产生重要作用,*Intentional weight loss in overweight individuals,Williamson DF, et al.,Diabetes Care,. 2000;23:1499-1504,.,-20%,-30%,整体死亡率,肿瘤死亡率,-40%,糖尿病相关死亡率,-50%,空腹血糖,体重降低,10%,降低体重将对2型糖尿病患者产生重要作用*Intentiona,2,2,型糖尿病患者,细胞功能进行性下降,Lebovitz.,Diabetes Reviews,1999;7:13953 (data are from the UKPDS population: UKPDS 16.,Diabetes,1995;44:124958),HOMA: homeostasis model assessment,2型糖尿病患者细胞功能进行性下降Lebovitz. Dia,3,6.2% ,正常值上限,HbA,1c,中位数,(%),常规治疗,*,时间,(,年,),罗格列酮,格列苯脲,二甲双胍,胰岛素,UKPDS,6,7,8,9,随机化后时间（年）,2,4,6,8,10,0,7.5,8.5,6.5,推荐治疗达标目标,15 mmol/L,则加用磺脲类,胰岛素和,/,或二甲双胍,美国糖尿病学会临床实践指南,.,UKPDS,n=1704,6.2% 正常值上限HbA1c 中位数(%)常规治疗*时,4,随治疗强化低血糖风险逐渐增加,Patients reporting,1 hypoglycaemic event/year (%),0.8%,1.7%,7.9%,21.2%,32.6%,p,0.0001,Wright,et al. J Diabetes Complicat,2006;20:395401,MET, metformin; SU, sulphonylurea,基础胰岛素,基础,+,餐前胰岛素,饮食控制,二甲双胍,磺脲类,低血糖事件发生,1,次,/,年的患者（,%,）,随治疗强化低血糖风险逐渐增加Patients reporti,5,2,型糖尿病的现状与挑战小结,随着生活方式的改变，中国糖尿病发病率不断增加，总发病率已达,9.7%,目前的治疗策略主要针对胰岛素抵抗、胰岛素分泌、抑制葡萄糖吸收,多数药物（胰岛素、磺脲类、格列酮类）治疗后导致体重进一步增加（,UKPDS, ACCORD,研究），治疗过程中低血糖的发生限制药物的应用和达标,2型糖尿病的现状与挑战小结随着生活方式的改变，中国糖尿病发病,6,八重奏,neurotransmitter dysfunction,八重奏neurotransmitter dysfunctio,7,Nauck MA, et al. J Clin Endocrinol Metab. 1986; 63: 492498.,口服糖耐量试验与静脉糖耐量试验,血糖,(mg/dL),时间,(,分钟,),C-,肽,(n,mol/L,),时间,(,分钟,),希望的曙光,“,肠促胰素效应”的发现,口服葡萄糖,静注葡萄糖,N=6,50 g,葡萄糖,80,年代通过检测,C,肽来反映胰岛素应答，确证了肠促胰素效应的存在,Nauck MA, et al. J Clin Endocr,8,2,型糖尿病中肠促胰素作用减弱,0,20,40,60,80,胰岛素,(mU/L),0,30,60,90,120,150,180,时间,(min),*,*,*,*,*,*,*,0,20,40,60,80,0,30,60,90,120,150,180,时间,(min),*,*,*,2,型糖尿病患者,正常人,静脉注射葡萄糖,口服葡萄糖,*,与口服后的相应值相比,p.05,Nauck MA, et al.,Diabetologia,. 1986;29:46-52.,2型糖尿病中肠促胰素作用减弱020406080胰岛素 (m,9,Strictly Confidential. Proprietary information of Novartis. For internal use ONLY. March 2010. GAL10.497. Novartis.,10,肠促胰素,Y,A,E,G,T,F,I,S,D,Y,S,I,A,M,D,K,I,H,Q,Q,D,F,V,N,W,L,L,A,Q,K,G,K,K,N,D,W,K,H,N,Q,T,I,GIP:,葡萄糖依赖性促胰岛素分泌多肽,H,A,E,G,T,F,T,S,D,V,S,S,Y,L,E,G,Q,A,A,K,E,F,I,A,W,L,V,K,G,R,G,GLP-1:,胰高糖素样肽,-1,Amino acids shown in orange are homologous with the structure of glucagon.,Strictly Confidential. Proprie,10,GLP-1,在人体中的作用,促进饱感,降低食欲,细胞,:,增强葡萄糖依赖的胰岛素分泌,肝脏,:,胰高糖素水平下降,减少肝糖输出,细胞,:,减少餐后胰高糖素分泌,胃,:,帮助调节胃排空,Adapted from Flint A, et al.,J Clin Invest,. 1998;101:515-520;,Adapted from Larsson H, et al.,Acta Physiol Scand,. 1997;160:413-422;,Adapted from Nauck MA, et al.,Diabetologia,. 1996;39:1546-1553;,Adapted from Drucker DJ.,Diabetes.,1998;47:159-169,.,进食促进,GLP-1,分泌,降低,细胞负荷,增加,细胞反应,GLP-1 在人体中的作用促进饱感细胞:增强葡萄糖依赖的,11,体内,GLP-1,被,DPP-4,降解及灭活,体内GLP-1 被 DPP-4 降解及灭活,12,GLP-1,作用小结,肠促胰素,增强葡萄糖依赖的胰岛素分泌,抑制胰高糖素分泌，减少肝糖输出,延缓胃排空,促进饱感，降低食欲,2,型糖尿病患者肠促胰素效应降低，其中,GLP-1,水平降低但作用正常,内源性,GLP-1,在体内被,DPP-4,酶降解,GLP-1作用小结肠促胰素,13,糖尿病治疗策略,依赖葡萄糖,GLP-1,(,艾塞那肽,）,-,葡糖苷酶抑制剂,(,阿卡波糖、米格列醇、伏格列波糖,),DPP-4,抑制剂,(,西,格,列汀,),不依赖葡萄糖,外源性胰岛素,格列奈类,磺脲类,罗格列酮,二甲双胍,吡格列酮,抑制葡萄糖吸收,胰岛素抵抗,胰岛素分泌,糖尿病治疗策略依赖葡萄糖GLP-1(艾塞那肽）-葡糖苷酶抑,14,与基线相比体重的平均变化,When BYETTA is used with an SFU, there is an increased risk of hypoglycaemia1.,Nauck MA, et al.,Mean (SE); N = 138; Evaluable meal tolerance cohort.,需注意过敏反应的症状或症候,体外试验中与人 细胞表面GLP-1受体结合,对GLP-1受体的激活作用至少和GLP-1相近,Blonde L, et al.,Diabetologia.,*与口服后的相应值相比p.,GLP1或DPP-4 或噻唑烷二酮,Intent-to-treat sample, N=138,2型糖尿病患者肠促胰素效应降低，其中GLP-1水平降低但作用正常,1998;101:515-520;,每天给药2次，给药时间为2顿主餐前1小时内*,Data on file, Amylin Pharmaceuticals, Inc.,治疗方案,目前治疗方案对体重的影响,体重,HbA1c 7%,1. Malone M.,Ann Pharmacother.,2005;39:2046,-,2055. 2. Glucotrol PI. New York, NY: Pfizer Inc; 2010. 3. Actos PI. Deerfield, IL: Takeda Pharmaceuticals America Inc; 2009. 4. Avandia PI. Research Triangle Park, NC: GlaxoSmithKline; 2007. 5. Nathan DM, et al.,Diabetes Care,. 2008;31:173-175. 6. Holman RR.,N Engl J Med.,2007;357:1716-1730. 7. Glucophage PI. Princeton, NJ: Bristol-Myers Squibb Company; 2009. 8. Januvia PI. Whitehorse Station, NJ: Merck and Company Inc; 2010. 9. Drucker DJ.,J Clin Invest,. 2007;117:24-32. 10. Golay A.,Int J Obes (Lond),. 2008;32:61-72.,P,P,P,P,P,P,*Approximately half of the studies in drug-nave T2D patients have shown significant weight loss with MET compared with baseline or comparator drugs; however, pooled analyses have suggested no significant effect vs placebo,10,See accompanying Prescribing Information and safety information included in this presentation,*,GLP-1,9,胰岛素,5,6,DPP-4,8,噻唑烷二酮,3,4,磺脲,1,2,二甲双胍,7,与基线相比体重的平均变化治疗方案目前治疗方案对体重的影响,15,艾塞那肽,(Exendin-4),人工合成的希拉巨蜥唾液中的一种蛋白质,与人,GLP-1,约有,53,的同源性,体外试验中与人,细胞表面,GLP-1,受体结合,对,GLP-1,受体的激活作用至少和,GLP-1,相近,能抵抗,DPP-4,降解灭活作用,艾塞那肽,:,一种,GLP,1,受体激动剂,Adapted from Nielsen LL, et al.,Regulatory Peptides,. 2004;117:77-88. Reprinted from,Regulatory Peptides, 117, Nielsen LL, et al, Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycaemic control of type 2 diabetes, 77-88, 2004, with permission from Elsevier for English use only.,DPP-4,灭活位点,H,G,E G T F T S D,L,S,K Q M,E,E E,A,V R L,F I,E,W L,K N,G,G P S S G A P P P S NH,2,H,A E G,T,F T S D V S,S Y,L,E G Q A A K E F I A W L V K G R NH,2,艾塞那肽,人,GLP-1,艾塞那肽 (Exendin-4)艾塞那肽: 一种GLP1受,16,艾塞那肽不被,DPP-4,降解,艾塞那肽不被DPP-4降解,17,GLP-1,葡萄糖依赖性的促进胰岛素分泌,300,200,100,0,胰岛素,(pmol/L),时间,(min),-30,0,60,120,180,240,*,*,*,*,*,*,*,*,安慰剂,GLP-1,葡萄糖,(mg/dL),270,180,90,0,-30,0,60,120,180,240,*,*,*,*,*,*,*,时间,(min),安慰剂,GLP-1,胰高糖素,(pmol/L),-30,0,60,120,180,240,20,10,0,时间,(min),*,*,*,*,安慰剂,GLP-1,安慰剂,GLP-1,N=10; Mean SEM; *p.05.,Nauck MA, et al.,Diabetologia,. 1993;36:741-744.,GLP-1 葡萄糖依赖性的促进胰岛素分泌300 200 10,18,2,型糖尿病患者,Beta,细胞功能进行性降低艾塞那肽可以促进,Beta,细胞增殖与新生,生理盐水,Exendin-4,艾塞那肽,每日一次治疗,2,周后增加糖尿病小鼠胰岛体积,100,80,60,40,2,型糖尿病诊断时间,(,年,),-,细胞,功能,(%),20,0,诊断当时仅余,50%,10,9,8,7,6,5,4,3,2,1,1,2,3,4,5,6,2型糖尿病患者Beta细胞功能进行性降低艾塞那肽可以促进B,19,Mean (SE); N=25.,Fehse F, et al.,J Clin Endocrinol Metab.,2005;90:5991-5997.,Copyright 2005, The Endocrine Society.,2,型糖尿病患者中短时间输注艾塞那肽可恢复,1,相胰岛素分泌,正常人，安慰剂,2,型糖尿病，安慰剂,2,型糖尿病，艾塞那肽,艾塞那肽,vs,安慰剂,p=.0002,p=.0002,时间,(min),胰岛素分泌,(pmolkg,-1,min,-1,),艾塞那肽使胰岛素和,C,肽的,AUC,0-10 min,和,AUC,10-120 min,增加约,180%310%,Mean (SE); N=25.2型糖尿病患者中短时间输注,20,艾塞那肽作用机制总结,调节摄食中枢*,延缓胃排空,抑制胰高糖素分泌,减少肝糖输出,血糖依赖性的控制胰岛素分泌,恢复第一时相胰岛素,保护,Beta,细胞,降低心血管风险及死亡率,减少并发症风险,When BYETTA is used with an SFU, there is an increased risk of hypoglycaemia,1. Kolterman OG, et al.,J Clin Endocrinol Metab,. 2003;88:3082-3089. 2. Nielsen LL, et al.,Regul Pept,. 2004; 117:77-88. 3. Fehse F, et al.,J Clin Endocrinol Metab,. 2005;90:5991-5997.,4. Blonde L, et al.,Diabetes Obes Metab,. 2006;8:436-447,.,See accompanying Prescribing Information and safety information included in this presentation,艾塞那肽作用机制总结调节摄食中枢*延缓胃排空抑制胰高糖素分泌,21,艾塞那肽临床研究历程,9,年以上,临床使用经验,1300,万,患者处方经验,发表了超过,723,篇论著，其中,125,篇经同行审阅,百泌达现已被包括,ADA/EASD,列入,2,型糖尿病治疗药物，并被列入,AACE/ACE,，,NICE,以及中国,2010,糖尿病防治指南,艾塞那肽临床研究历程9年以上1300万发表了超过723篇论著,22,See accompanying Prescribing Information and safety information included in this presentation,和胰岛素治疗,相比,单个口服药,失效,多个口服药,失效,百泌达,+,二甲双胍,+,磺脲类,(N=733),百泌达,+,二甲双胍,(N=336),百泌达,+,磺脲类,(N=377),百泌达,+,二甲双胍,+,磺脲类,vs,甘精胰岛素,+,二甲双胍,+,磺脲类,(N=551),百泌达,+,二甲双胍,+,磺脲类,vs,双相门冬胰岛素,+,二甲双胍,+,磺脲类,(N=501),百泌达,+,二甲双胍 或,磺脲类,vs,甘精胰岛素,+,二甲双胍 或,磺脲类,(N=138),百泌达,+,二甲双胍,vs,甘精胰岛素,+,二甲双胍,(N=69),百泌达,+,二甲双胍,vs,西格列汀,+,二甲双胍,(N=61),艾塞那肽的临床研究覆盖了,2,型糖尿病的不同治疗阶段,See accompanying Prescribing I,23,-0.5,-1.5,-1,0,-0.9,*,-0.6,*,+0.1,-0.7,-1.4,*,-1.9,*,-2.0,-1.5,-1.0,-0.5,0,ITT 30-week data; N = 1446; Mean (SE); *p0.005; Weight was a secondary endpoint.Data on file, Amylin Pharmaceuticals, Inc.,HbA,1c,变化,(%),体重变化,(kg),安慰剂,BID,艾塞那肽,5 g BID,艾塞那肽,10 g BID,AMIGO,研究（合并结果）：艾塞那肽降低,HbA1c,及体重,-0.5-1.5-10-0.9-0.6+0.1-0.7-1.,24,Diabetes Care.,10 g BID ,Data on file, Amylin Pharmaceuticals, Inc.,口服药治疗血糖控制不佳,Adapted from Drucker DJ.,2007;29:2333-2348.,Baseline Weight(kg),Adapted from Flint A, et al.,目前治疗方案对体重的影响,Glucophage PI.,Nielsen LL, et al.,基线ALT正常（n=101）,neurotransmitter dysfunction,MET, metformin; SU, sulphonylurea,细胞:增强葡萄糖依赖的胰岛素分泌,Mean (SE); N = 138; Evaluable meal tolerance cohort.,p12-16,24-28,100,0-4,16-20,20-24,28,4-8,8-12,0,15,30,45,60,75,安慰剂,5 g,艾塞那肽,BID,10 g,艾塞那肽,BID,体重减轻,0,-2,-4,体重减轻,(Kg),第,4,周时剂量从,5 g,增加至,10 g,的患者,AMIGO研究（合并结果）：恶心随时间延长而减少，而体重持续,26,开放性延长期研究,:,艾塞那肽治疗,82,周仍保持降低,HbA,1c,的作用,时间,(,周,),HbA,1c,平均变化,(%),0,10,20,30,40,50,60,70,80,90,-2.0,-1.5,-1.0,-0.5,0.0,0.5,安慰剂对照试验,均数,(SE); N = 393;,完成研究的受试者,; 82,周的数据,; 3,个组的基线,HbA,1c,平均为,8.3%,。,Data on file, Amylin Pharmaceuticals, Inc.,开放性延长期研究,(,所有受试者用,10 ,g,BID),安慰剂,10,g,艾塞那肽,BID,10,g,艾塞那肽,BID,10 ,g,BID,5 ,g,BID,10 g,艾塞那肽,BID,开放性延长期研究: 艾塞那肽治疗82周仍保持降低HbA1c的,27,开放性延长期研究,:,艾塞那肽治疗,82,周进行性降低体重,与基线相比体重的平均变化,(kg SEM),时间,(,周,),安慰剂对照试验,0,10,20,30,40,50,60,70,80,90,-5,-4,-3,-2,-1,0,开放性延长期研究,(,所有受试者用,10,g BID),均数,(SE); N = 393;,完成研究的患者,; 82,周的数据,;,体重变化是次要终点。基线体重,:,安慰剂组,= 98 kg, 5 g = 98 kg, 10 g = 100 kg.,Data on file, Amylin Pharmaceuticals, Inc.,安慰剂,10,g,艾塞那肽,BID,10,g,艾塞那肽,BID,10 ,g,BID,5 ,g,BID,10 g,艾塞那肽,BID,开放性延长期研究: 艾塞那肽治疗82周进行性降低体重与基线相,28,艾塞那肽治疗,3,年降低,HbA,1c,及体重,N=217; Mean,Adapted from Klonoff DC, et al.,Curr Med Res Opin,2008;24:275-286.,156,基线,99.3 1.2 kg,0,26,52,78,104,130,-6,-4,-2,0,156,周,-5.3 kg (95% CI: -6.0 to -4.5 kg;,p0.0001),治疗,(,周,),Weight Change from Baseline (kg),HbA,0,26,52,78,104,130,156,4,5,6,7,8,9,10,基线,8.2,0.1%,156,周,-1.0% (95% CI: -1.1 to -0.8%;,p0.0001),治疗,(,周,),1c,(%),艾塞那肽治疗3年降低HbA1c及体重N=217; Mean1,29,-5,-4,-3,-2,-1,0,1,2,3,4,5,-65,-55,-45,-35,-25,-15,-5,5,15,25,35,10%,68%,6%,16%,和基线相比,HbA1c (%),变化,和基线相比体重变化,(lbs),N=217Klonoff DC, et al.,Curr Med Res Opin.,2008;24:275-286.,See accompanying Prescribing Information and safety information included in this presentation,68%,的患者,HbA,1c,和体重均下降,-5-4-3-2-1012345-65-55-45-35-2,30,基线,HbA,1c,9%,的患者艾塞那肽治疗后,HbA,1c,降低更显著,2.5-year completers; n=241 at weeks 30 and 130; mean SE,Klonoff DC, et al. Curr Med Res Opin 2008;24:275-286,开放标签延伸期研究,基线,HbA1c (%),基线,HbA1c,9%,(n=59),9.7,基线,HbA1c 9%,(n=182),7.8,-2.5,-2.0,-1.5,-1.0,-0.5,0.0,30,周,156,周,-0.9%,-2.0%,-0.6%,-2.1%,Change in HbA1c (%),基线 HbA1c 9% 的患者艾塞那肽治疗后HbA1c降低,31,安慰剂对照开放延伸试验,(,合并,): 3.5,年时脂代谢改变,TG = triglycerides; SBP = systolic BP; DBP = diastolic BP,Klonoff DC, et al.,Curr Med Res Opin.,2008;24:275-286.,安慰剂对照研究,/,开放标签延伸期研究,(,合并,),平均变化,(%),N=151; *p.001,*p.05,TG,LDL,TC,*,*,*,+24%,-5%,-6%,-12%,-20,-15,-10,-5,0,5,10,15,20,25,30,SBP,DBP,- 4%,*,-2%,HDL,*,*,安慰剂对照开放延伸试验(合并): 3.5年时脂代谢改变 TG,32,安慰剂对照开放延伸试验,(,合并,):,基线时,ALT,升高组,3.5,年时,ALT,显著降低,Klonoff DC, et al. Curr Med Res Opin. 2008;24:275-286,Week 156 Between Group Difference:-1.7kg(95%Cl:-3.2 to -0.2kg;p=0.0266),基线,ALT,正常（,n=101,）,基线,ALT,升高（,n=116,）,Baseline Weight(kg),2,2,治疗（周数）,与基线相比体重的变化,(kg),0,26,52,78,104,130,156,0,-2,-4,-6,基线,ALT,正常（,n=101,）,基线,ALT,升高（,n=116,）,Baseline (IU/L),99+1,38,+,2,治疗（周数）,与基线相比,ALT,的变化,(IU/L),0,26,52,78,104,130,156,-12.5,-15.0,-10.5,-7.5,-5.0,-2.5,0,2.5,5.0,Week 156: -10IU/L (,95% CI: -13 to -8 IU/L),安慰剂对照开放延伸试验(合并): 基线时ALT升高组3.5年,33,艾塞那肽显著降低亚洲人群的,HbA,1c,与体重,HbA1c,改变（,%,）,体重改变（,Kg,）,Diabetes Research And Clinical Practice 83(2009):69-79,艾塞那肽显著降低亚洲人群的HbA1c与体重HbA1c改变（%,34,口服药治疗血糖控制不佳,Data on file, Amylin Pharmaceuticals, Inc.,与门冬胰岛素头对头对照试验：艾塞那肽能达到相似的血糖控制,和基线相比体重变化 (lbs),10 g 艾塞那肽 BID,2008;24:275-286.,艾塞那肽降低餐后2小时血糖的程度较西格列汀更大,2008;24:275-286.,Adapted from Nauck MA, et al.,百泌达最常见的不良事件包括恶心、轻到中度低血糖和上呼吸道感染,目前治疗方案对体重的影响,百泌达 何时启用，对患者获益更大?,甘精胰岛素 (n=127),Curr Med Res Opin 2008;24:275-286,艾塞那肽/甘精胰岛素对比试验: 治疗期间的体重变化,艾塞那肽用于亚洲人群,66%,的患者,HbA1c,与体重都降低,Diabetes Research And Clinical Practice 83(2009):69-79,安慰剂,艾塞那肽,与基线相比,A1C,（,%,）的变化,与基线相比体重（,kg,）的变化,0,2,4,6,-2,-4,-6,0,4,8,12,-4,-8,-12,艾塞那肽,:8%,安慰剂,:19%,艾塞那肽,:4%,安慰剂,:16%,艾塞那肽,:23%,安慰剂,:28%,艾塞那肽,:66%,安慰剂,:36%,口服药治疗血糖控制不佳艾塞那肽用于亚洲人群66%的患者HbA,35,AMIGO,研究及开放延伸试验小结,Klonoff DC, et al.,Curr Med Res Opin.,2008;24:275-286.,在用二甲双胍和,/,或磺脲类药物治疗的,2,型糖尿病患者中加用艾塞那肽治疗,3,年：,显著持续改善血糖控制,进行性降低体重,改善血脂、血压及,ALT,恶心随时间延长而减少，而体重持续减轻,在亚洲患者中艾塞那肽同样能显著降低,HbA1c,与体重,AMIGO研究及开放延伸试验小结Klonoff DC, et,36,艾塞那肽,/,甘精胰岛素对比试验,:,终点时,2,组,HbA,1c,降低相似,Intent-to-treat sample, N=138; LS mean SEM.,Barnett AH, et al.,Clin Ther.,2007;29:2333-2348.,-1.8,-1.6,-1.4,-1.2,-1.0,-0.8,-0.6,-0.4,-0.2,0,MET,SFU,in HbA,1c,变化,(%),艾塞那肽,(n=136),甘精胰岛素,(n=127),-1.43,-1.39,-1.27,-1.34,艾塞那肽/甘精胰岛素对比试验: 终点时 2组HbA1c 降低,37,艾塞那肽,/,甘精胰岛素对比试验,:,终点时,HbA1c,达标患者百分比,0,5,10,15,20,25,30,35,40,45,7.0% HbA,1c,6.5% HbA,1c,患者百分比,艾塞那肽,(n=136),甘精胰岛素,(n=127),Intent-to-treat sample, N=138,Barnett AH, et al. Clin Ther. 2007;29:2333-2348.,40,38,14,22,艾塞那肽/甘精胰岛素对比试验: 终点时 HbA1c 达标患,38,Intent-to-treat sample, N=138; LS mean SEM; *p.001, exenatide versus insulin glargine; *p=.016, exenatide versus insulin glargine.,Barnett AH, et al.,Clin Ther.,2007;29:2333-2348.,艾塞那肽,/,甘精胰岛素对比试验,:,餐后,2,小时血糖波动,-0.5,0,0.5,1.0,1.5,2.0,2.5,3.0,早晨,中午,晚上,*,*,*,餐后血糖波动,(mmol/L),艾塞那肽,(n=136),甘精胰岛素,(n=127),Intent-to-treat sample, N=138;,39,艾塞那肽,/,甘精胰岛素对比试验,:,治疗期间的体重变化,甘精胰岛素,艾塞那肽,时间,(,周,),0,2,4,6,8,12,16,18,20,22,24,28,32,体重变化,(kg),-,3,-,2,-,1,0,1,2,N=138; Intent-to-treat sample, LS mean SEM.,Barnett AH, et al.,Clin Ther.,2007;29:2333-2348.,n=70,n=68,艾塞那肽/甘精胰岛素对比试验: 治疗期间的体重变化甘精胰岛,40,艾塞那肽和甘精胰岛素相比：,HbA,1c,及体重变化,Data on file, Amylin Pharmaceuticals, Inc. and Lilly USA, LLC.,-5,-4,-3,-2,-1,0,1,2,3,11%,3%,24%,63%,百泌达,(n=231),甘精胰岛素,(n=245),5%,10%,63%,23%,和基线相比体重变化,(,磅,),和基线相比,HbA,1c,(%),变化,See accompanying Prescribing Information and safety information included in this presentation,-35,-25,-15,-5,5,15,25,35,艾塞那肽和甘精胰岛素相比：HbA1c及体重变化Data on,41,艾塞那肽,/,甘精胰岛素对比试验,:,低血糖发生率,艾塞那肽,(n=136),甘精胰岛素,(n=127),低血糖发生率,(%),0,5,10,15,20,25,30,35,40,所有患者,用二甲双胍,治疗的患者,用磺脲类药物,治疗的患者,*,Intent-to-treat sample, N=138; LS mean (SEM); *p=0.010,Barnett AH, et al.,Clin Ther.,2007;29:2333-2348.,25.2,14.7,2.6,17.4,34.5,30.0,艾塞那肽/甘精胰岛素对比试验: 低血糖发生率艾塞那肽 (n,42,HbA,1c,7%,治疗达标患者,(%),*,32%,24%,0,5,10,15,20,25,30,35,艾塞那肽,预混胰岛素,HbA,1c,变化,(%),-1.04%,-0.89%,-2.0,-1.5,-1.0,-0.5,0.0,ITT sample; left panel; ITT sample, mean change SE shown; NSD=nonsignificant differences;,Right panel: between-group difference *p=.038,Nauck MA, et al.,Diabetologia,. 2007;50:259-267.,-0.15% (95% CI, -0.32 to 0.01, p=.067),艾塞那肽,/,双相门冬胰岛素对比试验,:,终点时,HbA,1c,变化,HbA1c 7%治疗达标患者 (%)*32%24%0510,43,血糖,(mmol/L),*,*,*,早餐前,早餐后,午餐前,午餐后,晚餐前,晚餐后,03:00,7,8,9,10,11,12,13,艾塞那肽, 0,周,艾塞那肽, 52,周,7,8,9,10,11,12,13,预混胰岛素, 0,周,预混胰岛素, 52,周,早餐前,早餐后,午餐前,午餐后,晚餐前,晚餐后,03:00,ITT sample, mean (SE) shown; significantly lower mean glucose level observed for exenatide *p.001, premixed insulin *p=.0370; p=.0040; p=.002.,Nauck MA, et al.,Diabetologia,. 2007;50:259-267. Copyright 2007 Springer-Verlag. Reprinted with permission from Springer-Verlag.,艾塞那肽,/,双相门冬胰岛素对比试验,: 7,点自我血糖监测谱,血糖 (mmol/L)* 早餐前,44,时间,(,周,),体重变化,(kg),5.4 kg,*,*,0,2,4,8,12,16,28,40,52,-3,-2,-1,0,1,2,3,*,*,*,*,*,*,艾塞那肽,预混胰岛素,ITT sample, mean (SE) shown.,p.001, exenatide versus premixed insulin at postbaseline time points.,Nauck MA, et al.,Diabetologia.,2007;50:259-267. Copyright, 2007 Springer-Verlag. Reprinted with permission from Springer-Verlag,.,+2.9 kg,-2.5 kg,艾塞那肽,/,双相门冬胰岛素对比试验,:,体重变化,时间 (周)体重变化 (kg)5.4 kg*0248121,45,Nathan DM, et al.,10 g 艾塞那肽BID,Baseline (IU/L),2007;117:24-32.,1998;101:515-520;,HOMA: homeostasis model assessment,Data on