《糖尿病新药》PPT课件.ppt

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,20,30,18.5,25.0-9.9,30,BMI(kg/m2),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,降低体重将对2型糖尿病患者产生重要作用,*Intentional weight loss in overweight individualsWilliamson DF,et al.Diabetes Care.2000;23:1499-1504.,-20%,-30%,整体死亡率,肿瘤死亡率,糖尿病相关死亡率,-50%,空腹血糖,体重降低10%,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,HbA1c 中位数(%),常规治疗*,时间(年),罗格列酮,随着病程延长血糖控制逐渐恶化,UKPDS 34.Lancet 1998:352:85465;Kahn et al(ADOPT).NEJM 2006;355(23):242743,*最初采用饮食控制,如果空腹血糖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%,p0.0001,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,八重奏,neurotransmitter dysfunction,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(nmol/L),时间(分钟),希望的曙光“肠促胰素效应”的发现,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,2型糖尿病中肠促胰素作用减弱,Strictly Confidential.Proprietary information of Novartis.For internal use ONLY.March 2010.GAL10.497.Novartis.,11,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.,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,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 placebo10See 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 NH2,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 NH2,艾塞那肽,人GLP-1,艾塞那肽不被DPP-4降解,GLP-1 葡萄糖依赖性的促进胰岛素分泌,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,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,艾塞那肽 vs 安慰剂,p=.0002,p=.0002,时间(min),胰岛素分泌(pmolkg-1min-1),艾塞那肽使胰岛素和C肽的AUC0-10 min和AUC10-120 min增加约180%310%,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,When BYETTA is used with an SFU,there is an increased risk of hypoglycaemia1.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,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,ITT 30-week data;N=1446;Mean(SE);*p0.005;Weight was a secondary endpoint.Data on file,Amylin Pharmaceuticals,Inc.,HbA1c变化(%),体重变化(kg),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.p.0001 for change in PPG from baseline to week 30,exenatide vs placebo group.Data on file,Amylin Pharmaceuticals,Inc.,多个3期临床试验的合并结果,基线,血糖(mmol/L),30周,进餐,安慰剂,进餐,艾塞那肽,-30,0,30,60,90,120,150,180,5,8,11,13,16,15,14,12,10,9,7,6,5,-30,0,30,60,90,120,150,180,16,6,7,8,9,10,11,12,13,14,15,AMIGO研究（合并结果）：30周时艾塞那肽降低餐后血糖,AMIGO研究（合并结果）：恶心随时间延长而减少，而体重持续减轻,ITT 30-week data;N=1446.Data on file,Amylin Pharmaceuticals,Inc.,时间(周),恶心发生率(%),12-16,24-28,100,0-4,16-20,20-24,28,4-8,8-12,0,15,30,45,60,75,0,-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周仍保持降低HbA1c的作用,时间(周),HbA1c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HbA1c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,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HbA1c及体重,N=217;MeanAdapted 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,0,26,52,78,104,130,156,4,5,6,7,8,9,10,156 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HbA1c和体重均下降,基线 HbA1c 9%的患者艾塞那肽治疗后HbA1c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,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),艾塞那肽显著降低亚洲人群的HbA1c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,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HbA1c 降低相似,Intent-to-treat sample,N=138;LS mean SEM.Barnett AH,et al.Clin Ther.2007;29:2333-2348.,艾塞那肽/甘精胰岛素对比试验:终点时 HbA1c 达标患者百分比,Intent-to-treat sample,N=138Barnett 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：HbA1c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 HbA1c(%)变化,See accompanying Prescribing Information and safety information included in this presentation,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=0.010Barnett AH,et al.Clin Ther.2007;29:2333-2348.,25.2,14.7,2.6,17.4,34.5,30.0,HbA1c 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,HbA1c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=.038Nauck 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 HbA1c 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 SEAdapted from DeFronzo RA,et al.Curr Med Res Opin.2008;24(10)2943-2952.;Data on file,Amylin Pharmaceuticals,Inc.,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 min1.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 mealAdapted from DeFronzo RA,et al.Curr Med Res Opin.2008;24(10)2943-2952.,时间(分),标准餐,BaselineExenatideSitagliptin,-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 min1.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 failureNathan 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,HbA1c 6.5-7.5%,双药治疗,2-3个月,2-3个月,三药治疗,2-3个月,胰岛素辅助用药,HbA1c 7.5-9%,双药治疗,2-3个月,三药治疗,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,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,