北京大学第一医院内分泌内科主任医师、教授、博士生导师。曾任北京大学第一医院内科副主任，内分泌科主任，检验科主任。主要从事内分泌内科的医疗、
教学工作以及有关甲状腺疾病和糖尿病的临床研究和实验室研究工作。曾担任中华医学会内分泌分会副主任委员，现任中华医学会内分泌分会顾问。
任中华内科杂志中华内分泌代谢杂志等多家杂志编委。已培养出和正在培养多名硕士研究生和博士研究生，已有不少在国内内分泌领域成为学科带头
人。曾获中华医学会糖尿病学会以及内分泌学会终身成就奖。高妍教授独立互补协作创新更趋理想的新一代胰岛素IDegAsp的超长效/速
效的药代动力学特性药物特点说明书及共识循证医学证据理想的胰岛素类似物更好的模拟生理性胰岛素分泌目前胰岛素类似物的作用更为理想的胰岛
素类似物的作用速效胰岛素超速效胰岛素基础胰岛素超长效基础胰岛素预混胰岛素新一代胰岛素时间时间早餐午餐晚餐早餐午餐晚餐基础与速效胰岛
素类似物组成新型制剂的挑战地特胰岛素门冬胰岛素混合六聚体在常规制剂的条件下，地特胰岛素与速效胰岛素类似物混合，会形成混合六聚体，导
致两种胰岛素的药代动力学发生变化2地特胰岛素IGlarU100溶于pH4制剂速效胰岛素类似物溶于pH7.4制剂pH0
.07.014.0甘精胰岛素U100在pH4制剂可溶，在皮下组织的中性环境（pH7.4）成微沉淀物，但目前的速效胰岛素类似
物均需储存在pH7.4的制剂中1甘精胰岛素1.Lantus?USPrescribingInformation.Sano
fiApril2010;2.Jonassenetal.PharmRes2012;29:2104–14.在制剂中和
体内，德谷胰岛素和门冬胰岛素各自独立作用在制剂中在皮下储库德谷门冬双胰岛素(IDegAsp)=70%德谷胰岛素(IDeg)+
30%门冬胰岛素(IAsp)两种胰岛素各自独立存在于制剂中IDeg双六聚体IDegIAsp皮下缓慢解离迅速解离IAsp单六聚
体毛细血管Havelundetal.PharmRes2015;32:2250–8[Phenol;Zn2+]注
射后，IDegAsp在皮下发生变化IAsp单六聚体IDeg双六聚体注射后，进入皮下储库苯酚迅速弥散，德谷胰岛素由双六聚体链接
为多六聚体长链制剂中皮下门冬胰岛素单体迅速释放入血锌离子缓慢弥散，德谷胰岛素多六聚体缓慢解离，其单体缓慢释放入血Jonassen
etal.PharmRes2012;29:2104–14德谷胰岛素和门冬胰岛素各自独立存在于皮下组织0.401.000.7
00.300.500.900.600.000.100.200.80尺寸排阻色谱IDeg多六聚体IAsp单体吸收单位654141
3121110987分钟IAsp,门冬胰岛素;IDeg,德谷胰岛素Havelundetal.PharmRes201
5;32:2250–8IDegAsp的餐时和基础组份各自发挥独立的降糖作用在T1DM的患者中，IDegAsp达稳态时的葡萄糖输注率
IDegAsp0.6U/kg(n=22)餐时胰岛素组份基础胰岛素组份葡萄糖输注率(mg/kg/min)时间（小时）GIR：
葡萄糖输注率Heiseetal.DiabetesTher2014;5:255–65小结在制剂中或体内，德谷门冬双胰岛素
稳态时基础和餐时组份分别保留其超长效/速效的药代动力学特性，各自发挥独立的降糖作用德谷门冬双胰岛素中，门冬胰岛素组份在皮下迅速解离
，发挥餐时胰岛素作用；德谷胰岛素组份在皮下储库形成多六聚体长链，缓慢解离，发挥平稳的基础胰岛素作用IDegAspQD起始及BID
强化临床研究药物特点说明书及共识循证医学证据IDegAspIII期临床试验概述1型糖尿病未使用过胰岛素,2型糖尿病已使用过胰
岛素,2型糖尿病1型基础-餐时,n=548Onishi研究未使用过胰岛素,n=296STARTI未使用过胰岛素,n=5
30INTENSIFYBASALBOT,n=465QD1型儿童基础–餐时,n=362简单使用,n=276简单vs.逐步
Step-by-step既往BOT,n=532Chinaphase3（NN3598）INTENSIFYPREMIXI从
预混胰岛素强化,n=447STARTTWICEDAILY起始胰岛素,n=394INTENSIFYALL从任意胰岛素强
化,n=424TWICE-DAILYvsBB既往BOT,n=274BIDRAMADAN从任意胰岛素强化,n=250
SIMPLEvsSTEP-WISE既往BOT,n=272INTENSIFYBID从IDegAsp进行强化,n=40
简单调整vs.逐步调整vs.地特+门冬vs.门冬30vs.甘精U100vs.德谷+门冬vs.甘精+门冬BB
,基础-餐时;BID,每日两次；BOT,基础胰岛素+口服药;QD,每日一次Onishi研究：既往未
使用胰岛素治疗的2型糖尿病患者每日一次德谷门冬双胰岛素QD?OADs(n=147)既往未使用过胰岛素的2型糖尿病患者(n=
296)甘精胰岛素U100QD?OADs(n=149)026weeks入选标准2型糖尿病≥6个月至少12周使用≥1
种固定剂量的口服降糖药OADsHbA1c7.0–10.0%BMI≤35kg/m2年龄≥20岁随机化之前，停用SUs,
DPP-4抑制剂和格列奈类药物两组胰岛素起始剂量均为10U德谷门冬双胰岛素在每日主餐时使用;注射时间可由患者根据自己的意愿
选择IGlarU100根据说明书给药(根据患者意愿在早餐前或临睡时注射）在试验过程中注射时间不变BMI,体重指数;DPP
-4,二肽基肽酶-4,IDegAsp,德谷胰岛素/门冬胰岛素;IGlarU100,甘精胰岛素U100;OAD,口
服降糖药;QD,每日一次;SU,磺脲;T2D,2型糖尿病Onishietal.DiabetesObesMet
ab2013;15:826–32Onishi研究：人口统计学和基线特征德谷门冬双胰岛素QD甘精胰岛素QD纳入全分析集(F
AS),n147149女性/男性(%)38.8/61.233.6/66.4种族:亚裔(%)100.0100.0年龄(岁
)60.0(±10.0)61.0(±9.6)体重(kg)66.2(±13.4)66.4(±13.3)体质指数(kg/m
2)25.2(±3.8)25.0(±3.8)糖尿病病程(年)10.9(±7.3)12.4(±8.6)HbA1c(%)8
.3(±0.8)8.5(±0.8)空腹血糖(mmol/L)9.0(±1.6)9.1(±1.9)IDegAsp,德谷门冬
双胰岛素;IGlarU100,甘精胰岛素U100;QD,一天一次Onishietal.DiabetesObes
Metab2013;15:826–32Onishi研究：IDegAsp剂量调整原则早餐前/晚正餐前血浆葡萄糖a德谷门冬双胰
岛素或甘精胰岛素剂量调整mmol/LU<3.1b–4(若剂量>45U,减少10%)3.1–3.8b–2(若剂量>4
5U,减少5%)3.9–4.905.0–6.9+27.0–7.9+48.0–8.9+6≥9.0+8a3天连续至访视
点或电话随访前的平均值.b除非有明确的可解释的低血糖原因(如,漏进餐).Onishietal.DiabetesO
besMetab2013;15:826–32Onishi研究：IDegAsp每日一次注射时间德谷门冬双胰岛素QD(n=1
47)n(%)甘精胰岛素QD(n=149)n(%)总计(n=296)n(%)早餐前22(15.1)49(32.9)71
(24.1)午餐前6(4.1)0(0.0)6(2.0)晚餐前118(80.8)1(0.7)119(40.3)睡前
0(0.0)99(66.4)99(33.6)IDegAsp,德谷门冬双胰岛素;IGlarU100,甘精胰岛素U100
;QD,一天一次Onishietal.DiabetesObesMetab2013;15:826–32Onishi
研究：相比甘精胰岛素，IDegAsp控制HbA1c效果更优IDegAspQD(n=147)IGlarU100QD(n
=149)治疗差异:优效ETD:-0.28%-points[-0.46;-0.10],p<0.010.0时间(周)Mea
n±SEM;FAS,全集分析;LOCF,a末次观察推进法比较:多变量校正的估算ETD,估算的治疗差异;IDegAsp
,德谷门冬双胰岛素;IGlarU100,甘精胰岛素U100;QD,每日一次;T2D,2型糖尿病Onishiet
al.DiabetesObesMetab2013;15:826–32Onishi研究：相比甘精胰岛素，IDegAsp
血糖控制达标比例更高OR(IDegAsp/IGlar)2.10[1.26;3.52]p＜0.0170OR(IDegAsp/
IGlar)2.21[1.25;3.92]p＜0.01IDegAspQD(n=147)IGlarU100QD(n=1
49)(%)605059403020431040受试者比例(%)025HbA1c<7.0%且未发生低血糖HbA1c<7.0%Oni
shietal.DiabetesObesMetab2013;15:826–32.IDegAspQD(n=147)I
GlarU100QD(n=149)治疗差异:ETD:0.15mmol/L[-0.29;0.60]NS时间(周)Me
an±SEM;FAS,全集分析;LOCF,末次观察推进法比较:多变量校正的估算ETD,估算的治疗差异;FPG,空腹血糖
;IDegAsp，德谷门冬双胰岛素;IGlarU100,甘精胰岛素U100;NS,无显著性;QD,每日一次;T2
D,2型糖尿病Onishietal.DiabetesObesMetab2013;15:826–32Onishi研究
：相比甘精胰岛素，IDegAsp可达到相似的FPG控制Onishi研究：平均9点自我血浆葡萄糖检测谱(SMPG)情况IDe
gAsp组晚餐后PPG增幅显著优于甘精胰岛素组:ETD(IDegAsp–IGlarU100):–3.2[–4.08;–2
.31],p<0.0010周IDegAspQD(n=147)0周IGlarU100QD(n=149）26周IDegA
spQD(n=147)26周IGlarU100QD(n=149)14121086SMPG(mmol/L)0周9.0
9.1426周5.75.64:00h睡前早餐前早餐前午餐前晚餐前晚餐后90分钟午餐后90分钟早餐后90分钟IDegAsp,德谷
门冬双胰岛素;IGlarU100,甘精胰岛素U100;QD,一天一次;PPG，餐后血糖Onishietal.D
iabetesObesMetab2013;15:826–32;NN5401-3896(NCT01272193)Novo
NordiskClinicaltrialportal:http://www.novonordisktrials.com/W
ebSite/search/TrialDetail.aspx?Command=GetTrialDetail&TrialId=NN5
401-3896&Index=0http://www.novonordisktrials.com/WebSite/search/T
rialDetail.aspx?Command=GetTrialDetail&TrialId=NN5401-3896&Index=
0Onishi研究：总胰岛素剂量随时间变化情况IDegAspQD(n=147)IGlarU100QD(n=149)2
9U28U时间(周)SAS,安全性分析集;LOCF,末次观察推进法IDegAsp,德谷门冬双胰岛素;IGlarU10
0,甘精胰岛素U100;QD,每日一次;T2D,2型糖尿病Onishietal.DiabetesObesMe
tab2013;15:826–32;NN5401-3896(NCT01272193)NovoNordiskClinic
altrialportal:http://www.novonordisk-trials.com/WebSite/search
/TrialDetail.aspx?Command=GetTrialDetail&TrialId=NN5401-3896&Inde
x=0http://www.novonordisk-trials.com/WebSite/search/TrialDetail.a
spx?Command=GetTrialDetail&TrialId=NN5401-3896&Index=0Onishi研究：
相比甘精胰岛素，IDegAsp确证性低血糖事件数值更低IDegAspQD(n=147)IGlarU100QD(n=14
9)1.41.21.0任一组均无记录的严重低血糖事件0.8确证性低血糖(每位患者累计事件数)IDegAsp组降低27%ERR:
0.73[0.50;1.08]NS0.60.40.20.002468101214161820222426时间(周)SAS,
安全性分析集比较:多变量校正的估算ERR,预估的比率;IDegAsp,德谷门冬双胰岛素;IGlarU100,甘精胰岛
素U100;NS,无显著性;QD,每日一次;T2D,2型糖尿病Onishietal.DiabetesObes
Metab2013;15:826–32Onishi研究：相比甘精胰岛素，IDegAsp夜间确证性低血糖事件数值更低IDeg
AspQD(n=147)IGlarU100QD(n=149)0.270.240.210.18夜间确证性低血糖(每位患者累
计事件数)0.15IDegAsp组降低25%ERR:0.75[0.34;1.64]NS0.120.090.060.030.
0002468101214161820222426时间(周)SAS,安全性分析集比较:多变量校正的估算ERR,预估的比率;
IDegAsp,德谷门冬双胰岛素;IGlarU100,甘精胰岛素U100;NS,无显著性;QD,每日一次;T
2D,2型糖尿病Onishietal.DiabetesObesMetab2013;15:826–32Onishi研
究小结与甘精胰岛素相比，德谷门冬双胰岛素每日一次注射：降低HbA1c作用更优，达标率更高降低空腹血糖相似，同时兼顾餐后血糖控制总体
低血糖和夜间确证性低血糖的发生风险更低StepbyStep研究：既往使用基础胰岛素治疗且需要胰岛素强化治疗的T2DM患者St
epbyStep试验是一项为期38周、国际、开放标签、随机、治疗达标试验，共纳入来自7个国家的532例患者，观察在使用基础胰岛
素联用或不联用口服降糖药且需要胰岛素强化治疗的T2DM患者中，使用IDegAspQD与甘精胰岛素U100加用门冬胰岛素的疗效与安
全性。德谷门冬双胰岛QD/BID±OADs532例患者，随机分组(1:1)T2DM年龄≥18岁入组前使用基础胰岛素≥90
天±OADs至少90天(除外TZD)HbA1c7.0–10.0%德谷门冬双胰岛素QD±OADs主餐前注射甘精胰岛素Q
D+门冬胰岛素QD/BID/TID±OADs甘精胰岛素QD+门冬胰岛素QD/BID±OADs甘精胰岛素OD+门冬胰岛素QD
(主餐前注射)±OADs餐前血糖调整目标:4.0–5.0mmol/L32w38w0w26w研究中如果患者在26周或者32周时
HbA1c未达标(≥7%)，则通过增加注射次数或者增加餐时胰岛素实现进一步强化TZD:噻唑烷二酮；IDegAsp,德谷门冬双胰岛
素;IGlarU100,甘精胰岛素U100;OAD,口服降糖药;QD,每日一次;BID,每日二次；TID,
每日三次;T2D,2型糖尿病Philis-TsimikasAetal.DiabetesResClinPract
.2019Jan;147:157-165.StepbyStep研究：基线特征IDegAsp(N=267)Glargine
U100+IAsp(N=265)Total(N=532)性别:男性,n(%)125(46.8)137(51.7
)262(49.2)种族:白人,n(%)221(82.8)220(83.0)441(82.9)年龄,岁(
SD）58.2(8.9)59.2(9.1)58.7(9.0)体重,kg(SD)88.6(18.5)88.5(17
.5)88.6(18.0)BMI,kg/m2(SD)31.7(5.5)31.7(5.1)31.7(5.3)糖尿病病程
,年(SD)12.9(6.9)13.0(6.5)12.9(6.7)基线HbA1c值,%(SD)8.23(0.77
)8.13(0.73)8.18(0.75)基线FPG,mmol/L(SD)9.01(2.65)8.75(2.6
5)8.88(2.66)基线胰岛素治疗方案,n(%)基础胰岛素，QD基础胰岛素，BID217(81.3)50(
18.7)218(82.3)47(17.7)435(81.8)97(18.2)基线OAD治疗方法,n(%）无
1OAD2OADs>2OADs10(3.7)84(31.5)119(44.6)54(20.2)20
(7.5)82(30.9)116(43.8)47(17.7)30(5.6)166(31.2)235(44.
2)101(19.0)BID,一天两次;BMI,体质指数;FPG,空腹血糖;glargineU100,甘精胰岛
素100U/mL;IAsp,门冬胰岛素;IDegAsp,德谷门冬双胰岛素;n,患者例数;OAD,口服降糖药物;
QD,一天一次;SD,标准差.Philis-TsimikasAetal.DiabetesResClinPrac
t.2019Jan;147:157-165.StepbyStep研究：相比甘精胰岛素＋门冬胰岛素，IDegAsp在每日
注射次数更少的同时达到相似的HbA1c控制HbA1c较基线的变化(%)p=0.7938周(n=265)(n=265)26
周(n=267)(n=265)HbA1c＜7%的患者比例(%)p=0.728.238.138.238.13IDegAspIGl
ar+IAsp估计治疗差异0.07%(95%CI–0.06;0.21)估计治疗差异0.09%(95%CI–0.04;0
.22)38周时：IDegAsp组的平均每日注射次数1.62;甘精胰岛素＋门冬胰岛素组平均每日注射次数2.85Philis-T
simikasAetal.DiabetesResClinPract.2019Jan;147:157-165.St
epbyStep研究：相比甘精胰岛素＋门冬胰岛素，IDegAsp在每日注射次数更少的同时，空腹血糖和餐后SMBG增幅变化相
似空腹血糖较基线的变化(mmol/L)餐后SMBG增幅较基线的变化(mmol/L)38周(n=265)(n=265)26
周(n=267)(n=265)9.019.018.758.7538周(n=265)(n=265)26周(n=267)
(n=265)IDegAspIGlar+IAsp估计治疗差异0.10mmol/L(95%CI–0.24;0.43)估计治疗差
异0.30mmol/L(95%CI–0.01;0.62)-2.3-2.3-2.3估计治疗差异0.04mmol/L(95%
CI–0.34;0.42)估计治疗差异-0.24mmol/L(95%CI–0.60;0.13)38周时：IDegA
sp组的平均每日注射次数1.62;甘精胰岛素＋门冬胰岛素组平均每日注射次数2.85Philis-TsimikasAetal
.DiabetesResClinPract.2019Jan;147:157-165.StepbyStep研究：平
均9点自我血浆葡萄糖检测谱(SMPG)情况IDegAsp(Baseline)IDegAsp(26weeks)IDegAs
p(38weeks)IGlarU100+IAsp(Baseline)IGlarU100+IAsp(26wee
ks)IGlarU100+IAsp(38weeks)SMPG(mmol/L)0Philis-TsimikasAe
tal.DiabetesResClinPract.2019Jan;147:157-165.StepbyStep
研究：相比甘精胰岛素＋门冬胰岛素，IDegAsp显著降低夜间低血糖风险RR0-38周:0.61[0.40;0.93]95
%CIp=0.023RR0-38周:0.86[0.65;1.14]95%CIp=0.291RR0-26周:0.55
[0.34;0.90]95%CIp=0.018RR0-26周:0.90[0.67;1.22]95%CIp=0.51
3IDegAsp夜间确证性低血糖风险显著降低严重或确证性低血糖事件两组相似39%低血糖发生次数/例患者45%低血糖发生次数/例患者
时间(周)时间(周)IDegAspIGlar+IAspPhilis-TsimikasAetal.DiabetesRes
ClinPract.2019Jan;147:157-165.StepbyStep研究：相比甘精胰岛素＋门冬胰岛素，ID
egAsp显著减少胰岛素日总剂量，未显著增加体重胰岛素日总剂量减少(U)两组体重变化相似(kg)估计治疗差异:0.16kg[
-0.47;0.79],p=0.611889.3U估计治疗差异:0.43kg[-0.13;0.99],p=0.1286
79.4U83.4UIDegAspIGlar+IAspTreatmentratio:0.91[0.83;0.99]95
%CIp=0.031770.9UTreatmentratio:0.88[0.81;0.95]95%CIp=0.0018
研究终点胰岛素日剂量：IDegAspvs.IGlar+IAsp：83.4uvs.89.3u，P=0.0317研究终点
体重变化：IDegAspvs.IGlar+IAsp：+2.55kgvs.+2.39kg，P=0.6118Philis
-TsimikasAetal.DiabetesResClinPract.2019Jan;147:157-165.
StepbyStep研究：研究期间的胰岛素方案0周26周32周63%100%57%IDegAspBIDIDegAspBIDI
DegAsp(N=242)IDegAspQD43%37%IDegAspQDIDegAspQD32%100%49%IGlar+IAs
pTIDIGlar+IAspBIDIGlar+IAsp(N=243)23%IGlar+IAspBIDIGlar+IAsp
QD51%45%IGlar+IAspQDIGlar+IAspQDPhilis-TsimikasAetal.Diabet
esResClinPract.2019Jan;147:157-165.StepbyStep研究：IDegAsp无需
调整基础和餐时胰岛素比例，治疗更简便餐时基础基础-餐时比例(%)基础-餐时比例(%)IDegAspIGlar+IAsp餐时
30基础701周26周38周Philis-TsimikasAetal.DiabetesResClinPract.2
019Jan;147:157-165.StepbyStep研究小结与基础-餐时方案相比，德谷门冬双胰岛素有效性安全性HbA
1c降幅相似FPG降幅相似降低PPG增幅相似显著降低夜间低血糖风险注射次数更少总剂量更少体重变化相似IDegAsp临床应用指南及共
识药物特点说明书及共识循证医学证据适应症及使用方法用于治疗成人2型糖尿病，包括老年、肝肾功能损害的2型糖尿病患者治疗成人、青少
年及2岁以上儿童糖尿病，包括老年、肝肾功能损害的2型糖尿病患者和1型糖尿病患者需要胰岛素治疗的糖尿病，包括成人、1岁及以上儿童和青
少年糖尿病患者、老年糖尿病患者、肝肾功能损害的糖尿病患者和1型糖尿病患者1岁及以上糖尿病患者，包括老年糖尿病患者和1型糖尿病患者中
国欧洲日本美国德谷门冬双胰岛素注射液说明书剂量指导德谷门冬双胰岛素可随主餐每日一次或每日两次给药本品可单独给药，也可与口服抗糖尿病
药物联合使用，或与餐时胰岛素联合使用注：主餐在美国和欧洲说明书中定义为main/largestmeal每日总起始剂量为10单位，
餐时给药，随后进行个体化剂量调整德谷门冬双胰岛素注射液说明书转换方法转换前方案转换方案每日1次基础或预混胰岛素等剂量转换为QD，总
剂量不变＞每日1次基础或预混胰岛素等剂量转换为BID，总剂量不变基于个体需要进行。通常以相同单位数量的基础胰岛素剂量开始治疗基础/
餐时胰岛素治疗改用本品期间及后续数周内建议密切监测血糖。可能需要调整联合使用的速效或短效胰岛素药品或其他伴随的抗糖尿病治疗药物的剂
量和给药时间。德谷门冬双胰岛素注射液说明书IDegAsp临床使用共识情况临床使用方法起始强化/转换IDegAsp临床应用患者特
点目前用药有效性需求安全性需求灵活方便性需求建议使用方法多种口服药改善血糖控制降低低血糖风险，尤其是夜间低血糖更灵活的注射时间ID
egAspQD基础胰岛素改善PPG控制降低低血糖风险，尤其是夜间低血糖更灵活的注射时间IDegAspQD预混胰岛素（QD)或基
础+餐时胰岛素（QD)改善血糖控制降低低血糖风险，尤其是夜间低血糖更灵活的注射时间，更少注射次数IDegAspQD预混胰岛素BI
D改善血糖控制降低低血糖风险，尤其是夜间低血糖更灵活的注射时间IDegAspBID基础+餐时胰岛素（BID/TID）降低血糖波动
降低低血糖风险，尤其是夜间低血糖更灵活的注射时间，更少注射次数转换为IDegAspQD或IDegAspBIDQD,每日一次;
BID,每日二次；PPG，餐后血糖KalraS,eta.lIndianJEndocrMetab2016;2
0:542-5.总结在制剂中或体内，IDegAsp的基础和餐时组份各自独立发挥作用全球III期研究为IDegAspQD,BID
在胰岛素起始和强化方案中的使用提供了证据支持和具体临床指导：IDegAspQD起始治疗：较甘精胰岛素的HbA1C控制更优，FPG
控制相似，兼顾PPG有效控制，总体和夜间低血糖风险更低IDegAspBID强化治疗：较基础-餐时方案的HbA1C控制相似，低血糖
风险特别是夜间低血糖风险更低，胰岛素日剂量更少全球多国专家共识对IDegAsp的使用方法和注意事项进行不断的优化补充谢谢！The
actionprofilesofmoderninsulins,whileanimprovementonhuma
ninsulin,donotaccuratelymimicthephysiologicalreleaseofe
ndogenousinsulin.Therefore,theaimoffutureinsulinsistomo
recloselymimictheendogenousresponse.IGlarandIDetcannotbe
coformulatedwithbolusinsulins.IGlarisdesignedtomicroprec
ipiateatpH4whilebolusinsulinisonlysolubleatpH7.4,there
bycreatingadisconnect.IDetwhencoformulatedcanleadtothe
formationofmixedhexamerswhichdistortsthePK/PDprofileoft
heinsulinIDegAspisthefirstco-formulation.Itiscomposedof
70%IDegand30%IAsp.Thetwoinsulinsexistseparatelyinthep
en(IDegasdihexamersandIAspashexamers).Uponinjectioninto
thesubcutaneousspacetheIAsphexamersrapidlydissociateand
enterthebloodstream,whileIDegformsmultihexamerchainsthat
slowlydissociate德谷胰岛素在制剂中呈双六聚体，两端为苯酚分子封闭了形成多六聚体的可能。注射入皮下后，苯酚分子迅
速弥散，德谷胰岛素六聚体两端打开，相互链接成多六聚体。Thekineticpropertiesofbasalinsuli
nshavethepotentialtobeimprovedusingacetylationbyfattya
cids.Thisenablessoluble,highmolecularweightcomplexestofo
rmpost-injection.Jonassenetal(2012)examinedaseriesofins
ulins,acetylatedatB29withfattyacidsviaglutamicacidspace
rs,todeducethestructuralrequirements.Theyfoundthatwithd
epletionofphenolinsulin,degludecformedhighmolecularmassf
ilament-likecomplexes,whichdisintegratedwithdepletionofzin
c.Circulardichroismspectroscopy(CDS)showedtheseanaloguesa
doptingstableT3R3conformationinpresenceofphenolandzinc,
changingtoT6withdepletionofphenol.Thesefindingssuggesti
nsulindegludecisdihexamericinpharmaceuticalformulation,bec
omingmultihexamericafterinjection.Theanaloguesshowedweakd
imericassociation,indicatingrapidreleaseofmonomersfollowin
ghexamerdisassembly.Theauthorsconcludedthatinsulinscanbe
engineeredthatremainsolublebutbecomehighlyself-associated
afterinjection,slowlyreleasingmonomers;thisiscriticallyd
ependentontheacylationmoiety.Onesuchanalogue,insulindegl
udec,hastherapeuticpotential.Apotentiallyimportantconsequen
ceofthepropertyofIDegformingverystableT3R3dihexamersin
apharmaceuticalformulation(andmultihexamersatthesiteofi
njection)isthatotherinsulins(e.g.rapid-actinginsulins)can
beco-formulatedwithouttheriskofinter-exchangeofmonomers
toformhybridhexamerseitherinthecartridgeorinjectiondepo
t.Thiscouldenablethedevelopmentofcombinationproductswith
discretepreservationofthePKprofilesofthecomponentinsuli
nsSize-ExclusionChromatography尺寸排除色谱法:更大的胰岛素分子滤出更快，更小的分子经过孔隙的时候
会停留因此更长时间渗出。Size-exclusionchromatography(SEC)wasperformedto
characterizetheassociationstatesfortheindividualbasaland
rapid-actinginsulins,andforthecombinations.ThreeSECmethod
swereusedasinvitromodelstosimulateconditionsinthephar
maceuticalformulation(athighconcentrationofphenolandroom
temperature),theconditioninthesubcutaneousdepotafterinjec
tion(withoutphenolandatbodytemperature)and,finally,toev
aluateaserialdecreaseinconcentrationofphenolandm-cresol,
asexpectedtooccurfollowingsubcutaneousinjection.Furthermo
re,fractionsofhighandlowmolarmasswerecollectedfromthe
SECeluents,andreverse-phasechromatographywasusedtomeasure
theconcentrationsoftheindividualinsulinwithinthem.SECmet
hod1wasdesignedtosimulateconditionsinthepharmaceuticalf
ormulation(withthesamephenolconcentration),andwasusedto
measurethepercentageofoligomersofdihexamer,dihexamers,hex
amers,andmonomerswitheluentof16?mMphenol,140?mMsodiumch
loride,10?mMtris(hydroxymethyl)aminomethane(tris)pH?7.3,an
d0.01%sodiumazideat23°C.Thesize-exclusioncolumnusedwas
ACQUITYUPLC?BEH200(1504.6?mm,d=?1.7?μm)fromWatersCorpora
tion,Milford,MA,USA.Ultravioletdetectionwavelengthswereat
286,276and290?nmformethods1–3,respectively.Injectionvol
umewas20?μLandflowwas0.15?mL/min.SECmethod2wasdesigned
tosimulateconditionsinthesubcutaneousdepot(inwhichphenol
quicklydissipates),andwasusedtomeasurethepercentageofm
ultihexamerversusthehexamer–monomerfractionwithaphenol-fre
eeluentof140?mMsodiumchloride,10?mMtrispH?7.3,0.01%sodi
umazide,and5%2-propanolat37°C.Theconcentrationsofthein
dividualinsulinanalogsinthemultihexamerfractionandthehex
amer–monomerfractionweredeterminedbyreverse-phasechromatogr
aphy.ASymmetryShieldRP18(3.920?mm,d?=?3.5?μm)columnfromW
atersCorporation(Milford,MA,USA)waselutedwithA:10%(vol)
acetonitrile0.2?Msodiumsulfate,40?mMo-phosphoricacidadjus
tedtopH?3.6withsodiumhydroxideandB:70%(vol)acetonitrile
atagradientof20–54%at1.4–5?minat30°C,1?mL/min,anddete
ctionat276?nm.Toavoidadsorption,70?ppmpolysorbate20wasa
ddedtothefractionvials.Forcomparison,insulindetemirwasco
mbinedwithinsulinaspartinthesameproportions(volume70:30)
andstoredfor4?weeksat25°C.SECmethod2wasmodifiedforth
ecombinationofinsulindetemirandinsulinaspartbydividingf
ractioncollectionbetweenhexameranddimer(sinceinsulindetem
irachievesitsprotractedabsorptionlargelythroughreversible
albuminbindingratherthanmultihexamerformation).SECmethod1
wasnotemployedforaninsulindetemirandinsulinaspartcombin
ation.ThisisbecauseinthephenolicSECeluent(similartothe
pharmaceuticalformulation),insulindetemirelutesasahexamer
,asdoesinsulinaspart,sothetwoinsulinanalogs(andanyhyb
ridassociations)wouldthereforebeindistinguishableusingthis
method.SECmethod3wasdesignedtosimulateserialconditionsa
tdecreasingconcentrationsofthepreservativesphenolandm-cre
sol,aswilloccurimmediatelyaftersubcutaneousinjection.Thes
etestsweremadebymixingA:16?mMphenolandm-cresol,20?mMs
odiumchloride,3?mMsodiumdihydrogenphosphatepH?7.3,and0.01%
sodiumazide,withB:140?mMsodiumchloride,3?mMsodiumdihydr
ogenphosphatepH?7.3,and0.01%sodiumazideat37°C.Transformat
ionofinsulindegludecdihexamerstomultihexamers,andofinsul
inasparthexamerstomonomers,wascomparedwithhumaninsulin.A
bstractPURPOSE:Tostudytheself-associationstatesofinsulind
egludecandinsulinaspartaloneandcombinedinpharmaceuticalf
ormulationandunderconditionssimulatingthesubcutaneousdepot
.METHODS:Formulationsweremadeof0.6mMdegludecat3and5Zn
/6insulinmonomers,and0.6mMaspart(2Zn/6insulinmonomers).
Self-associationwasassessedusingsize-exclusionchromatograph
y(SEC)monitoredbyUVandorthogonalreverse-phasechromatograp
hy.RESULTS:Simulatingpharmaceuticalformulation,degludecelute
dasdihexamers,whereasaspartelutedashexamersandmonomers.
Combiningdegludecatlowzincwithaspartincreaseddihexamerco
ntent,indicatinghybridhexamerformation.Athighzincconcentr
ation,however,therewasnoevidenceofthis.Simulatingthesub
cutaneousdepotbyremovingpreservative,degludecelutedasmult
ihexamersandaspartasmonomers.Aspartwasincorporatedintoth
emultihexamerstructureswhencombinedwithdegludecatlowzinc
,buttherewasnosuchinteractionwithhigh-zincdegludec.SEC
usingprogressivelydilutedconcentrationsofphenolandm-cresol
showedthatdissociationofaspartintomonomersoccursbeforet
heformationofdegludecmultihexamers.CONCLUSION:Insulinsdeglu
decandaspartcanbecombinedwithoutforminghybridhexamers,b
utthiscombinabilityisdependentonzincandpreservativeconce
ntration,andrequiresthatdegludecisfullydihexamericbefore
additionofaspart.Themeanglucoseinfusionrate(GIR)profiles
howedarapidonsetofactionandadistinctpeakfollowedbyaf
latbasalaction.Thereisaclearanddistinctseparationofthe
individualeffectsoftherapid-actingandbasalcomponents.The
blueshadedarearepresentsIDeg0.4U/kgdatafromthe1993stud
y.AUCGIR,tau,SS(mg/kg) Geometricmean(CV) 3859.1(32.8)Min
;Max 1452.1;6115.895%CI 3261.9;4565.6GIRmax,SS(mg/[kg?m
in])N 22Geometricmean(CV) 7.0(34.6)Min;Max 2.8;12.095%CI
5.9;8.3tGIRmax,SS(h)N 22Median(CV) 2.5(29.9)Min;Max
1.8;4.895%CI 2.1;3.1CV,coefficientofvariationin%CI,co
nfidenceintervalTheconfidenceintervalforthemeanwascalcula
tedusingat-distributionandlog-transformationoftheendpoint
.FortGIRmax,Hodges–Lehmann95%CIsarepresentedABSTRACTIntrod
uction/aim:Insulindegludec/insulinaspart(IDegAsp)isasolubl
eco-formulationoflong-actingandshort-actinginsulinanalogs.
Theprimaryobjectiveofthisstudywastoinvestigatethepharm
acodynamicresponseofonce-dailyIDegAspdosinginpatientswith
type1diabetes.Pharmacokineticresponse,aswellassafetyand
tolerability,wereassessedassecondaryobjectives.Methodology:
Thiswasasingle-center,open-label,single-armstudy.Twenty-t
wosubjectsreceivedonce-dailyinsulindegludec(IDeg)(0.42U/k
g)forfiveconsecutivedays[withseparatebolusinsulinaspart
(IAsp)asneededforsafetyandglycemiccontrol],toachievecli
nicalsteadystateofthebasalcomponent.OnDay6,theyreceive
dasingleinjectionofIDegAsp(0.6U/kg,comprising0.42U/kgI
Degand0.18U/kgIAsp).Pharmacodynamicresponsewasassessedus
inga30-heuglycaemicglucoseclamp,withbloodglucosestabiliz
edatatargetof5.5mmol/L.Results:Theglucoseinfusionratep
rofileshowedarapidonsetofactionandadistinctpeakdueto
IAsp,followedbyaseparate,flatandstablebasalglucose-lower
ingeffectduetotheIDegcomponent.Modelingdatasuggestedtha
tthepharmacodynamicprofileofIDegAspwasretainedwithtwice-
dailydosing(allowingforcoverageoftwomainmealsdaily).IDe
gAspwaswelltoleratedandnosafetyissueswereidentifiedint
histrial.Conclusions:Inconclusion,theIAspcomponentofIDegA
sphasafastonsetofappearanceandapeakcoveringtheprandia
lphase,whiletheIDegcomponenthasaflatandanevenlydistri
butedpharmacokineticprofileover24h.IDegAspisthefirstco-
formulationofabasalinsulinanalogwithanultra-longduration
ofactionandamealtimeinsulinanaloginasinglesolubleinje
ction.Thesepropertiestranslateintoclinicallyrelevantbenefi
ts,includingimprovedglycemiccontrolandreductioninhypoglyc
emia.ThisslideprovidesanoverviewoftheBOOSTclinicalprogra
mmetrials,listingkeyparametersbytrialphaseandbypatient
groupTheoverviewhighlightsthebreathofpopulationsinwhichI
DegAsphasbeenstudied.TrialdesignforBOOSTJAPAN.Thiswasa
open-label26-weektrial.Patientswhomettheinclusioncriteria
wererandomised1:1toonce-dailyinjectionsofIDegAsporinsul
inglargineU100(IGlarU100),both±≤2oralantidiabetictreatme
nts.IDegAspwasgivenbeforethelargestmealatthediscretion
ofeachsubject(andmaintainedthroughoutthetrial);IGlarU100
wasdosedaccordingtolabel.Bothinsulinsweretitratedtoat
argetpre-breakfastself-measuredplasmaglucoseof3.9to<5.0m
mol/L.AbstractAims:Thisphase3,26-week,open-label,treat-to-t
argettrialinvestigatedtheefficacyandsafetyofinsulindeglu
dec/insulinaspart(IDegAsp)ininsulin-naiveJapaneseadultswit
htype2diabetes.Methods:Subjectswererandomizedtoonce-daily
injectionsofIDegAsp(n=147)orinsulinglargine(IGlar)(n=149
),both±≤2oralantidiabetictreatments.IDegAspwasgivenbefor
ethelargestmealatthediscretionofeachsubject(andmaintai
nedthroughoutthetrial);IGlarwasdosedaccordingtolabel.Bo
thinsulinsweretitratedtoatargetprebreakfastself-measured
plasmaglucoseof3.9to<5.0mmol/l.Results:After26weeks,mean
HbA1cwas7%withIDegAspand7.3%withIGlar;superiorityofID
egAsptoIGlarwasshown(estimatedtreatmentdifference,ETD;ID
egAsp–IGlar:–0.28%points[?0.46;–0.10]95%CI,p<0.01).Atend-
of-trial,meanfastingplasmaglucose(FPG)wassimilarforIDegA
spandIGlar(5.7vs.5.6mmol/l;ETDIDegAsp–IGlar:0.15mmol/l
[?0.29;0.60]95%CI,p=NS).IDegAspwasassociatedwithnumerical
lylowerratesofoverallconfirmed(27%)andnocturnalconfirmed
hypoglycaemia(25%)versusIGlar(estimatedrateratioIDegAsp/I
Glar:0.73[0.50;1.08]95%CI,p=NS,and0.75[0.34;1.64]95%CI,
p=NS,respectively).Meandailyinsulindosesweresimilarbetwe
engroupsatend-of-trial(both:0.41U/kg)asweretheincreases
inbodyweightfrombaseline(both:0.7kg).Adverseeventprofi
lesweresimilarbetweengroups.Conclusions:IDegAspprovidedsup
eriorlong-termglycaemiccontrolcomparedtoIGlar,withsimilar
FPGanddosesandnumericallylowerratesofoverallandnocturn
alhypoglycaemia(p=NS).HbA1cresultsforBOOSTJAPANattheend
ofthetrial(6months)After26weeksoftreatment,meanHbA1chad
decreasedby1.4±0.9%pointsfrombaselineintheIDegAspgroup
andby1.2±1.0%pointsintheIGlarU100grouptomeanvaluesof
7±0.8and7.3±0.9%,respectively.AnalysisofchangeinHbA1cfro
mbaselineshowedthatIDegAspwassuperiortoIGlarU100;thees
timatedmeantreatmentdifference(IDegAsp–IGlarU100)was?0.28%
points[?0.46;–0.10]p<0.01.AbstractAims:Thisphase3,26-week
,open-label,treat-to-targettrialinvestigatedtheefficacyand
safetyofinsulindegludec/insulinaspart(IDegAsp)ininsulin-n
aiveJapaneseadultswithtype2diabetes.Methods:Subjectswere
randomizedtoonce-dailyinjectionsofIDegAsp(n=147)orinsulin
glargine(IGlar)(n=149),both±≤2oralantidiabetictreatments.
IDegAspwasgivenbeforethelargestmealatthediscretionofe
achsubject(andmaintainedthroughoutthetrial);IGlarwasdose
daccordingtolabel.Bothinsulinsweretitratedtoatargetpre
breakfastself-measuredplasmaglucoseof3.9to<5.0mmol/l.Resu
lts:After26weeks,meanHbA1cwas7%withIDegAspand7.3%with
IGlar;superiorityofIDegAsptoIGlarwasshown(estimatedtreat
mentdifference,ETD;IDegAsp–IGlar:–0.28%points[?0.46;–0.10]
95%CI,p<0.01).Atend-of-trial,meanfastingplasmaglucose(FP
G)wassimilarforIDegAspandIGlar(5.7vs.5.6mmol/l;ETDIDe
gAsp–IGlar:0.15mmol/l[?0.29;0.60]95%CI,p=NS).IDegAspwasa
ssociatedwithnumericallylowerratesofoverallconfirmed(27%)
andnocturnalconfirmedhypoglycaemia(25%)versusIGlar(estima
tedrateratioIDegAsp/IGlar:0.73[0.50;1.08]95%CI,p=NS,and
0.75[0.34;1.64]95%CI,p=NS,respectively).Meandailyinsulin
dosesweresimilarbetweengroupsatend-of-trial(both:0.41U/k
g)asweretheincreasesinbodyweightfrombaseline(both:0.7
kg).Adverseeventprofilesweresimilarbetweengroups.Conclusio
ns:IDegAspprovidedsuperiorlong-termglycaemiccontrolcompare
dtoIGlar,withsimilarFPGanddosesandnumericallylowerrate
sofoverallandnocturnalhypoglycaemia(p=NS).FPGresultsforB
OOSTJAPANattheendofthetrial(6months)MeanFPGdecreasedb
y3.3±2.4mmol/LfrombaselineintheIDegAspgroupandby3.5±2.
4mmol/LintheIGlarU100group(figure2B)tomeanend-of-trial
valuesof5.7±2.1and5.6±1.9mmol/L,respectively.Therewasno
statisticallysignificantdifferencebetweentreatments[estimat
edtreatmentdifference:0.15mmol/L(?0.29;0.60)(NS)].Abstract
Aims:Thisphase3,26-week,open-label,treat-to-targettrialin
vestigatedtheefficacyandsafetyofinsulindegludec/insulinas
part(IDegAsp)ininsulin-naiveJapaneseadultswithtype2diabe
tes.Methods:Subjectswererandomizedtoonce-dailyinjectionsof
IDegAsp(n=147)orinsulinglargine(IGlar)(n=149),both±≤2or
alantidiabetictreatments.IDegAspwasgivenbeforethelargest
mealatthediscretionofeachsubject(andmaintainedthroughout
thetrial);IGlarwasdosedaccordingtolabel.Bothinsulinswe
retitratedtoatargetprebreakfastself-measuredplasmaglucose
of3.9to<5.0mmol/l.Results:After26weeks,meanHbA1cwas7%
withIDegAspand7.3%withIGlar;superiorityofIDegAsptoIGlar
wasshown(estimatedtreatmentdifference,ETD;IDegAsp–IGlar:–
0.28%points[?0.46;–0.10]95%CI,p<0.01).Atend-of-trial,mean
fastingplasmaglucose(FPG)wassimilarforIDegAspandIGlar(
5.7vs.5.6mmol/l;ETDIDegAsp–IGlar:0.15mmol/l[?0.29;0.60]9
5%CI,p=NS).IDegAspwasassociatedwithnumericallylowerrates
ofoverallconfirmed(27%)andnocturnalconfirmedhypoglycaemia
(25%)versusIGlar(estimatedrateratioIDegAsp/IGlar:0.73[0.
50;1.08]95%CI,p=NS,and0.75[0.34;1.64]95%CI,p=NS,respect
ively).Meandailyinsulindosesweresimilarbetweengroupsate
nd-of-trial(both:0.41U/kg)asweretheincreasesinbodyweigh
tfrombaseline(both:0.7kg).Adverseeventprofilesweresimil
arbetweengroups.Conclusions:IDegAspprovidedsuperiorlong-ter
mglycaemiccontrolcomparedtoIGlar,withsimilarFPGanddoses
andnumericallylowerratesofoverallandnocturnalhypoglycaem
ia(p=NS).InsulindoseresultsforBOOSTJAPANattheendofthe
trial(6months)Attheendofthetrial,themeandailyIDegAspa
ndIGlarU100dosesweresimilarbetweentreatmentgroups:28U(0
.41U/kg)forIDegAspand29U(0.41U/kg)forIGlarU100.Themean
andmediandifferencebetweentheprescribeddoseandtheactual
dosetakenbythepatientwasveryclosetozero(0)andthestan
darddeviationwaslowthroughoutthetrialforbothtreatmentgr
oups,indicatingacloseadherencetothetitrationalgorithm.In
theIDegAspgroup,81%ofthepatientsadministeredthedailydo
sepriortotheeveningmeal,15%priortobreakfastand4%prior
tolunch.IntheIGlarU100group,66%ofpatientsadministered
thedailydoseatbedtime,33%priortobreakfastand1%priorto
theeveningmeal.AbstractAims:Thisphase3,26-week,open-label
,treat-to-targettrialinvestigatedtheefficacyandsafetyofi
nsulindegludec/insulinaspart(IDegAsp)ininsulin-naiveJapanes
eadultswithtype2diabetes.Methods:Subjectswererandomizedt
oonce-dailyinjectionsofIDegAsp(n=147)orinsulinglargine(I
Glar)(n=149),both±≤2oralantidiabetictreatments.IDegAspwas
givenbeforethelargestmealatthediscretionofeachsubject
(andmaintainedthroughoutthetrial);IGlarwasdosedaccording
tolabel.Bothinsulinsweretitratedtoatargetprebreakfastse
lf-measuredplasmaglucoseof3.9to<5.0mmol/l.Results:After2
6weeks,meanHbA1cwas7%withIDegAspand7.3%withIGlar;super
iorityofIDegAsptoIGlarwasshown(estimatedtreatmentdiffere
nce,ETD;IDegAsp–IGlar:–0.28%points[?0.46;–0.10]95%CI,p<0.
01).Atend-of-trial,meanfastingplasmaglucose(FPG)wassimil
arforIDegAspandIGlar(5.7vs.5.6mmol/l;ETDIDegAsp–IGlar:
0.15mmol/l[?0.29;0.60]95%CI,p=NS).IDegAspwasassociatedwi
thnumericallylowerratesofoverallconfirmed(27%)andnocturn
alconfirmedhypoglycaemia(25%)versusIGlar(estimatedraterat
ioIDegAsp/IGlar:0.73[0.50;1.08]95%CI,p=NS,and0.75[0.34;
1.64]95%CI,p=NS,respectively).Meandailyinsulindosesweres
imilarbetweengroupsatend-of-trial(both:0.41U/kg)asweret
heincreasesinbodyweightfrombaseline(both:0.7kg).Adverse
eventprofilesweresimilarbetweengroups.Conclusions:IDegAsp
providedsuperiorlong-termglycaemiccontrolcomparedtoIGlar,
withsimilarFPGanddosesandnumericallylowerratesofoverall
andnocturnalhypoglycaemia(p=NS).Cumulativerateofconfirmed
hypoglycaemiaforBOOSTJAPANattheendofthetrial(6months)T
heestimatedrateofconfirmedhypoglycaemiawasnumericallylowe
r(by27%)withIDegAspthanwithIGlarU100;theestimatedrate
ratio(IDegAsp/IGlarU100)was0.73[0.50;1.08]95%CI,NS.Abstra
ctAims:Thisphase3,26-week,open-label,treat-to-targettrial
investigatedtheefficacyandsafetyofinsulindegludec/insulin
aspart(IDegAsp)ininsulin-naiveJapaneseadultswithtype2dia
betes.Methods:Subjectswererandomizedtoonce-dailyinjections
ofIDegAsp(n=147)orinsulinglargine(IGlar)(n=149),both±≤2
oralantidiabetictreatments.IDegAspwasgivenbeforethelarges
tmealatthediscretionofeachsubject(andmaintainedthrougho
utthetrial);IGlarwasdosedaccordingtolabel.Bothinsulins
weretitratedtoatargetprebreakfastself-measuredplasmagluco
seof3.9to<5.0mmol/l.Results:After26weeks,meanHbA1cwas7
%withIDegAspand7.3%withIGlar;superiorityofIDegAsptoIGl
arwasshown(estimatedtreatmentdifference,ETD;IDegAsp–IGlar:
–0.28%points[?0.46;–0.10]95%CI,p<0.01).Atend-of-trial,me
anfastingplasmaglucose(FPG)wassimilarforIDegAspandIGlar
(5.7vs.5.6mmol/l;ETDIDegAsp–IGlar:0.15mmol/l[?0.29;0.60
]95%CI,p=NS).IDegAspwasassociatedwithnumericallylowerrat
esofoverallconfirmed(27%)andnocturnalconfirmedhypoglycaem
ia(25%)versusIGlar(estimatedrateratioIDegAsp/IGlar:0.73[
0.50;1.08]95%CI,p=NS,and0.75[0.34;1.64]95%CI,p=NS,respe
ctively).Meandailyinsulindosesweresimilarbetweengroupsat
end-of-trial(both:0.41U/kg)asweretheincreasesinbodywei
ghtfrombaseline(both:0.7kg).Adverseeventprofilesweresim
ilarbetweengroups.Conclusions:IDegAspprovidedsuperiorlong-t
ermglycaemiccontrolcomparedtoIGlar,withsimilarFPGanddos
esandnumericallylowerratesofoverallandnocturnalhypoglyca
emia(p=NS).Cumulativerateofnocturnalconfirmedhypoglycaemia
forBOOSTJAPANattheendofthetrial(6months)Theestimatedr
ateofnocturnalconfirmedhypoglycaemiawasnumericallylower(b
y25%)withIDegAspthanwithIGlarU100;theestimatedraterati
o(IDegAsp/IGlarU100)was0.75[0.34;1.64]95%CI,NSAbstractAim
s:Thisphase3,26-week,open-label,treat-to-targettrialinves
tigatedtheefficacyandsafetyofinsulindegludec/insulinaspar
t(IDegAsp)ininsulin-naiveJapaneseadultswithtype2diabetes
.Methods:Subjectswererandomizedtoonce-dailyinjectionsofID
egAsp(n=147)orinsulinglargine(IGlar)(n=149),both±≤2oral
antidiabetictreatments.IDegAspwasgivenbeforethelargestmea
latthediscretionofeachsubject(andmaintainedthroughoutth
etrial);IGlarwasdosedaccordingtolabel.Bothinsulinswere
titratedtoatargetprebreakfastself-measuredplasmaglucoseof3.9to<5.0mmol/l.Results:After26weeks,meanHbA1cwas7%withIDegAspand7.3%withIGlar;superiorityofIDegAsptoIGlarwasshown(estimatedtreatmentdifference,ETD;IDegAsp–IGlar:–0.28%points[?0.46;–0.10]95%CI,p<0.01).Atend-of-trial,meanfastingplasmaglucose(FPG)wassimilarforIDegAspandIGlar(5.7vs.5.6mmol/l;ETDIDegAsp–IGlar:0.15mmol/l[?0.29;0.60]95%CI,p=NS).IDegAspwasassociatedwithnumericallylowerratesofoverallconfirmed(27%)andnocturnalconfirmedhypoglycaemia(25%)versusIGlar(estimatedrateratioIDegAsp/IGlar:0.73[0.50;1.08]95%CI,p=NS,and0.75[0.34;1.64]95%CI,p=NS,respectively).Meandailyinsulindosesweresimilarbetweengroupsatend-of-trial(both:0.41U/kg)asweretheincreasesinbodyweightfrombaseline(both:0.7kg).Adverseeventprofilesweresimilarbetweengroups.Conclusions:IDegAspprovidedsuperiorlong-termglycaemiccontrolcomparedtoIGlar,withsimilarFPGanddosesandnumericallylowerratesofoverallandnocturnalhypoglycaemia(p=NS).一项为期50周、多中心、随机、开放、平行对照、治疗达标研究，比较口服降糖药控制不佳的2型糖尿病患者接受门冬胰岛素30为主1-2-3针治疗对比以基础胰岛素为主阶梯治疗的疗效和安全性。纳入OADs控制不佳的T2DM患者（n=403），随机分为两组：门冬胰岛素30组（n=203）和基础-餐时方案组（n=200）。从第0周开始，两组患者分别给予门冬胰岛素301针和地特胰岛素1针治疗；在第14周、26周和38周，如果患者HbA1c＜7.0%，则增加注射针数，分别增加门冬胰岛素30或餐时胰岛素，治疗50周观察治疗效果。NoadditionalbolusinsulinwasadministeredintheIDegAspgroup.RyzodegcanbeadministereddiabetesmellitusinadultsinChina.Patientswithtype1diabetesmellitusandPaediatricpopulationcanbecoveredinJapan,USandEurope.Ryzodegcanbeadministeredonceortwicedailywiththemainmeal(s).Inpatientswithtype2diabetesmellitus,thisinsulincanbeadministeredalone,incombinationwithoralantidiabeticmedicinalproducts,andincombinationwithbolusinsulinTherecommendedtotaldailystartingdoseis10unitswithmeal(s)followedbyindividualdosageadjustments.Patientsswitchingfromonce-dailybasalorpremixinsulintherapycanbeconvertedunit-to-unittoonce-dailyRyzodegatthesametotalinsulindoseasthepatient’sprevioustotaldailyinsulindose.Patientsswitchingfrommorethanonce-dailybasalorpremixinsulintherapycanbeconvertedunit-to-unittotwice-dailyRyzodegatthesametotalinsulindoseasthepatient’sprevioustotaldailyinsulindose.Patientsswitchingfrombasal/bolusinsulintherapytoRyzodegwillneedtoconverttheirdosebasedonindividualneeds.Ingeneral,patientsareinitiatedonthesamenumberofbasalunits. |
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