肠促胰素和2型糖尿病.ppt

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,*,肠促胰素和2型糖尿病,中国糖尿病患病发病率已达9.7%,N Engl J Med 2010;362:1090-1101,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,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,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,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（%）,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,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,Strictly Confidential.Proprietary information of Novartis.For internal use ONLY.March 2010.GAL10.497.Novartis.,12,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.,体内GLP-1 被 DPP-4 降解及灭活,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,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,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,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GLP1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,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.,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,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,-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,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,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,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,(%),-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,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(%),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):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),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%,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,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 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,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),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/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,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,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,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,比较研究总结：艾塞那肽和胰岛素血糖改善作用相似,与甘精胰岛素头对头对照试验：艾塞那肽能达到相似的血糖控制,艾塞那肽减轻体重,甘精胰岛素增加体重,艾塞那肽能提供更严格的餐后血糖控制，甘精胰岛素降低更多空腹血糖,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,艾塞那肽减轻体重,预混胰岛素增加体重,对于空腹血糖作用相似,艾塞那肽更好地控制餐后血糖，更多患者达到HbA1c 7.0%,2-hr PPG(mg/dL),阶段1,终点,阶段2,终点,After Period 1,patients were switched to the other therapy;Patients with T2D;Evaluable population:exenatide-sitagliptin,n=29;sitagliptin-exenatide,n=32;Mean SE,Adapted from DeFronzo RA,et al.,Curr Med Res Opin.,2008;24(10)2943-2952.;Data on file,Amylin Pharmaceuticals,Inc.,艾塞那肽,西他列汀,基线,110,130,150,170,190,210,230,250,270,艾塞那肽降低餐后2小时血糖的程度较西格列汀更大,胰岛素分泌指数,1,艾塞那肽,西格列汀,Patients with T2D;Evaluable population,n=61 for both treatment groups;Geometric LS mean SE,Standard meals administered at t=0 min,1.Adapted from DeFronzo RA,et al.,Curr Med Res Opin.,2008;24(10)2943-2952.;2.Data on file,Amylin Pharmaceuticals,Inc.,基线时胰岛素分泌指数,几何平均数,2,:0.4,0.55,P,=0.02,0.82,0.4,0.5,0.6,0.7,0.8,0.9,1.0,0.55,0.82,艾塞那肽较西格列汀更大程度地改善胰岛素分泌指数,Patients with T2D;Evaluable population,n=61 for all treatment groups;Mean SD;Acetaminophen was administered immediately before the standard meal,Adapted from DeFronzo RA,et al.,Curr Med Res Opin.,2008;24(10)2943-2952.,时间(分),标准餐,Baseline,Exenatide,Sitagliptin,-30,0,30,60,90,120,150,180,210,240,0.0,2.5,5.0,7.5,10.0,12.5,15.0,17.5,20.0,血浆乙酰氨基酚(ug/ml),艾塞那肽延缓胃排空，西格列汀无此作用,和基线相比热量摄入变化(kcal),1,Patients with T2D;Evaluable ad lib cohort,n=25 for both treatment groups;LS mean SE Standard meals administered at t=0 min,1.Adapted from DeFronzo RA,et al.,Curr Med Res Opin.,2008;24(10)2943-2952.;2.Data on file,Amylin Pharmaceuticals,Inc.,基线平均热量摄入,2,:1071 kcal,艾塞那肽,西格列汀,P,=0.0227,-134,+130,-200,-100,0,100,200,300,-134,+130,-300,艾塞那肽降低平均热量摄入,艾塞那肽对西格列汀作用机制研究:总结,DeFronzo RA,et al.,Curr Med Res Opin.,2008;24(10)2943-2952,.,艾塞那肽较西格列汀显著降低餐后2小时血糖,和西格列汀相比，艾塞那肽能引起,更大幅度的降低：,整个餐后时间段的血糖,餐后血糖波动,餐后胰高糖素水平,胰岛素分泌指数的改善,延缓胃排空,减少热量摄入,空腹血糖的变化艾塞那肽和西格列汀相似,百泌达 何时启用，对患者获益更大?,百泌达在2型糖尿病的治疗地位,See accompanying Prescribing Information and safety information included in this presentation,口服药治疗血糖控制不佳,超重,/,肥胖或饮食控制困难,寻求最佳的治疗方案,单一口服药,口服药联合治疗,胰岛素治疗,饮食控制和运动,ADA/EASD 关于2型糖尿病的共识声明,诊断:,生活方式,+,二甲双胍,生活方式+二甲双胍,+,基础胰岛素,生活方式+二甲双胍,+,磺脲类,生活方式+二甲双胍,+,强化胰岛素,第一步,第二步,第三步,生活方式+二甲双胍,+,吡格列酮,(无低血糖/有水肿(心衰)/骨丢失),第一级:有很多寻证医学支持的核心治疗,第二级:寻证医学证据较少的核心治疗,生活方式+二甲双胍,+,GLP-1 受体激动剂,b,(无低血糖/可降低体重/恶心/呕吐),生活方式+二甲双胍,+,吡格列酮,+,磺脲类,a,生活方式+二甲双胍,+,基础胰岛素,CHF=congestive heart failure,Nathan DM,et al.,Diabetes Care,2009;32:193-203.,GLP-1受体激动剂在AACE/ACE 糖尿病血糖控制原则中的地位,生活方式干预,单药治疗,二甲双胍,噻唑烷二酮,DPP-4酶抑制剂,糖苷酶抑制剂,HbA1c 6.5-7.5%,双药治疗,二甲双胍,GLP1,或DPP-4,噻唑烷二酮,格列奈或磺脲类,噻唑烷二酮,GLP1,或DPP4,二甲双胍,考来维仑,糖苷酶抑制剂,2-3个月,2-3个月,三药治疗,二甲双胍,GLP1,或DPP-4,噻唑烷二酮,格列奈或磺脲类,2-3个月,胰岛素辅助用药,HbA1c 7.5-9%,双药治疗,二甲双胍,GLP1,或DPP-4 或噻唑烷二酮,磺脲类或格列奈,2-3个月,三药治疗,二甲双胍,GLP1,或DPP-4,噻唑烷二酮,GLP1,或DPP-4,磺脲类,噻唑烷二酮,胰岛素辅助用药,HbA1c 9%,未经治疗,2-3个月,已治疗,有症状,无症状,胰岛素辅助用药,二甲双胍,GLP1,或DPP-4,磺脲类,噻唑烷二酮,GLP1,或DPP-4,噻唑烷二酮,胰岛素辅助用药,Helena W.Rodbard,et al.,ENDOCRINE PRACTICE Vol 15 No.6 September/October 2009,百泌达：起始方便、治疗简单,首次注射后,百泌达预充笔可在低于25C的室温中保存,每支预充笔可使用一个月,每天给药2次，给药时间为2顿主餐前1小时内*,无需根据进餐量或运动量调整剂量,无需额外监测血糖,第一个月5ug每天两次，第二个月开始10ug每天两次,*两餐之间至少间隔6小时,详见相关的使用说明和安全信息,5 g BID,10 g BID,百泌达不良反应总结,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,3年研究中仅5%的患者因恶心退出研究,因低血糖退出者1%,恶心的预防与管理,控制进食速度,当感到有胀满感时停止进食,进餐前15分钟内注射可以减少恶心,试着变更注射时间，但必须在注射后1小时内进食,当患者耐受5微克剂量后才开始启动10微克每天两次的剂量,如果在注射10微克剂量后发生明显的恶心，可以恢复到5微克每天两次的剂量，在经过一段时间后再提高剂量,百泌达重要安全性信息,BYETTA,European Package Insert,2007.,注意事项,百泌达 不能代替胰岛素，用于1型糖尿病或糖尿病酮症酸中毒的治疗。,使用百泌达的患者需注意急性胰腺炎的症状或症候（持续的、严重的腹痛，可伴有呕吐）。如果怀疑有急性胰腺炎，需停用百泌达或其它可疑药物。如果胰腺炎被确诊，且未发现其它可能的胰腺炎的病因，则不建议重新使用百泌达,需注意过敏反应的症状或症候,谢谢,