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AimsWhatistheidealHbA1c?LegacyeffectBloodPressure:canwegotoolow?Cholesteroltargets,andtheroleofFibratesWhoshouldhaveaspirin?CaseScenariosWhatdrugstouseaftermetformin?Whentouseinsulinandwhichone?Anythingelse?AimsWhatistheidealHbA1c?LWhatistheidealHbA1cUKPDSdataDCCTandEDICtrialADVANCEACCORDSTENOVADT

WhatistheidealHbA1cUKPDSdHbA1c

cross-sectional,medianvaluesHbA1ccross-sectional,median糖尿病研究最新进展(2011年)课件UKPDS80–LegacyofLong-termGlycaemicControl(30YearFollowUpData)UKPDS80–LegacyofLong-termAftermedian8.5yearspost-trialfollow-up

AggregateEndpoint

1997

2007Anydiabetesrelatedendpoint RRR:

12%

9%

P:

0.029

0.040

Microvasculardisease RRR:

25%

24%

P:

0.0099

0.001Myocardialinfarction RRR: 16% 15%

P:

0.052

0.014All-causemortality RRR: 6% 13%

P:

0.44

0.007RRR=RelativeRiskReduction,P=LogRankLegacyEffectofEarlierGlucoseControlAftermedian8.5yearspost-trACCORDADVANCEandVADT-NoSignificantEffectonMacroVascularOutcomesACCORDADVANCEVADTNo.ofparticipants10,25111,1401791Participantage,years626660Durationofdiabetesatstudyentry,years10811.5HbA1CatBaseline,%8.17.59.4Participantswithpriorcardiovascularevent,%353240Durationoffollow-up,years3.45.06ACCORDADVANCEandVADT-NoSiSummaryofACCORD,ADVANCEandVADT:Outcomes,intensivevs.standardACCORDADVANCEVADTHbA1c,%6.4vs.7.5*6.5vs.7.3*6.9vs.8.4*Deathfromanycause,%

5.0vs.4.0*8.9vs.9.6NADeathfromcardiovascularevent,%

2.6vs.1.8*4.5vs.5.22.1vs.1.7NonfatalMI,%

3.6vs.4.6*2.7vs.2.86.1vs.6.3Nonfatalstroke,%

1.3vs.1.23.8vs.3.82.0vs.3.1Neworworseningnephropathy,%

NA4.1vs.5.2*NAMajor/severehypoglycemia,%

10.5vs.3.5*2.7vs.1.5*21.1vs.9.7*Weightgain,kg3.5vs.0.4*0.0vs.-1.0*NA*p≤0.05

SummaryofACCORD,ADVANCEand糖尿病研究最新进展(2011年)课件ACCORDRetinalConclusionIntensiveglycemiccontrolandintensivecombinationtreatmentofdyslipidemia,butnotintensiveblood-pressurecontrol,reducedtherateofprogressionofdiabeticretinopathy.(FundedbytheNationalHeart,Lung,andBloodInstituteandothers;ClinicalTnumbers,NCT00000620fortheACCORDstudyandNCT00542178fortheACCORDEyestudy.)‏ACCORDRetinalConclusionIntenADVANCE4.3yearsoffollow-up:Perindopril/indapamideBloodpressurereduced7.1±0.3mmHgsystolicand2.9±0.2mmHgdiastolic(P<0.001).135/75:140/77(baseline145/81)HbA1Cwasreducedby0.61±0.02%after4.3years(P<0.001).GlicazideMRADVANCE4.3yearsoffollow-up:糖尿病研究最新进展(2011年)课件VADTConclusionIntensiveglucosecontrolinpatientswithpoorlycontrolledtype2diabeteshadnosignificanteffectontheratesofmajorcardiovascularevents,death,ormicrovascularcomplications,withtheexceptionofprogressionofalbuminuria(P=0.01)VADTConclusionIntensiveglucoVADTintheContextofthe“NaturalHistory”ofType2DiabetesTime(yearssincediagnosis)HbA1c(%)6.06.57.07.58.08.59.09.512345678910111213141516DrivetheriskforcomplicationsVADTintheContextofthe“NaMeanSystolicBlood-PressureLevelsatEachStudyVisitTheACCORDStudyGroup.NEnglJMed2010;362:1575-1585MeanSystolicBlood-PressureLACCORDBPConclusionInpatientswithtype2diabetesathighriskforcardiovascularevents,targetingasystolicbloodpressureoflessthan120mmHg,ascomparedwithlessthan140mmHg,didnotreducetherateofacompositeoutcomeoffatalandnonfatalmajorcardiovasculareventsACCORDBPConclusionInpatientACCORDlipidConclusionThecombinationoffenofibrateandsimvastatindidnotreducetherateoffatalcardiovascularevents,nonfatalmyocardialinfarction,ornonfatalstroke,ascomparedwithsimvastatinaloneTheseresultsdonotsupporttheroutineuseofcombinationtherapywithfenofibrateandsimvastatintoreducecardiovascularriskinthemajorityofhigh-riskpatientswithtype2diabetesACCORDlipidConclusionThecomHazardRatiosforthePrimaryOutcomeinPrespecifiedSubgroupsTheACCORDStudyGroup.NEnglJMed2010;362:1563-1574HazardRatiosforthePrimary糖尿病研究最新进展(2011年)课件DiabetesandAspirinGuidanceYesinsecondarypreventionPrimarypreventionshouldbeonanindividualbasiswithconsiderationofthebenefitsandharmsofaspirin,takingintoaccountthepresenceofriskfactorsforvasculardisease(includingconditionssuchasdiabetes)andtheriskofgastrointestinalbleeding..MHRADrugSafetyUpdate.October2009.DiabetesandAspirinGuidanceYDiabetesandAspirinGuidancePrimaryprevention:over50,smoker,treatedforhypertensionandhighcholesterol:yesUnder50withallfactorsandFH:yesfromage40Under50:noOver50non-smokeronlyDM:noOver50treatedforhypertension,andhighcholesterol:probablyyesDiabetesandAspirinGuidancePAspirinandDiabetesTheASCENDStudyisalargemultisitestudyrecruiting10,000patientsover40withtype2diabetesdesignedtoanswerthequestionwhetheraspirinshouldbeprescribedroutinelyindiabeticpatients.(2011)ACCEPT-DItalianstudy5000patients,greaterthan50.(aspirin/placebo)2007startedAspirinandDiabetesTheASCENDNICEGuidelines:GeneralRecommendations

Structureddiabeteseducation,andaimforgoodglucosecontrolearlyoninthediagnosis(metforminearly).TargetHbA1cof6.5%forType2Diabetesingeneral,butavoidpursuinghighlyintensivemanagementoflevelslessthan7%inthosewithlimitedlifeexpectancy5years),especiallyifusingdrugswhichcangeneratehypoglycaemiaBloodpressuretargetoflessthan140/80mmHg(Nolegacyeffect)Simvastatin40mgorequivalentforallpatientswithType2diabetesagedover40,irrespectiveofexperienceofCVdisease.NICEGuidelines:GeneralRecomMonotherapywith1stor2ndGenerationSUswasAssociatedwith24-61%ExcessRiskForAllCauseMortalityComparedwithMetforminMonotherapy(P<0.001)2.01.51.00.51stGenerationsulphonylureasvmetformin2ndGenerationsulphonylureasvmetforminAllrosiglitazone*vmetforminAllpioglitazone*vmetforminAllrosiglitazone*vallpioglitazone*Othercombinations†vmetforminTzoulakietal.,BMJ2009;339:b4731HazardRatio(95%CI)(LogScale)*Anytherapy(monotherapyandcombinations).†OtherdrugsandcombinationsofanyoralantidiabetesdrugsexcludingrosiglitazoneandpioglitazoneModel2resultsMonotherapywith1stor2ndGeACCORD:MortalityHRforIndividualAgents1ACCORDStudyGroup.EffectsofIntensiveGlucoseLoweringinType2Diabetes.NEnglJMed2008;358:2545-592.ACCORDWebcastpresentedattheAmericanDiabetesAssociation,6-10June2008.Availableat:/StoreTemplate/default.aspx?ReturnUrl=%2fDefault.aspx5.Cefalu,WT.NEnglJMed2008;358(24):2633-2635.6.AvandiaSPCMarch2008ACCORD:MortalityHRforIndivA40yearoldSupermarketWorkerA40yearoldladyhasa2yearhistoryoftype2diabetes.Herglycaemiccontrolisconsistentlypoor.Sheisanex-smokerwithaBMIof49.HercurrentmedicationincludesAspirin75mgOD,Lisinopril20mgOD,Simvastatin20mgOD,Metformin850mgBD.ExaminationrevealBPof175/70mm/hg,peripheralpulsesarenormalwithnoevidenceofneuropathy.Fundoscopyrevealsearlybackgroundretinopathy.Hba1c-8.5%TC-5.7mmol/lLDL-C-3.5mmol/lHDL-C-0.9mmol/lPlasmaTG-2.6mmol/lU/E-NormalLFT-NormalMicroalbuminuriascreen-positiveHowwouldyoufurthermanagethispatient?A40yearoldSupermarketWorkPATIENTMRSX78type2DMBMI28HbA1C8.5%,nocomplicationsMetforminintolerant?MetforminMRBP145/89,NormalACR,Chol6.5,Hdl1.3SUs,PioGlitazone,or(Sita)gliptinTargetHbA1c?PATIENTMRSX78type2DMBMI糖尿病研究最新进展(2011年)课件糖尿病研究最新进展(2011年)课件OPTionsBMI>35gliptin?Exenatide,avoidsulphonylureasearlyElderlyavoidsulphonylureasearly,aimforreasonablecontrolHbA1c7.5%BMI<30SusafterMetforminBMI30-35age,renalfunction,weightchanges,?SU,gliptinorPioglitazonesecond.KnownIHDconsiderPioglitazoneaftermetforminunlessheartfailureOPTionsBMI>35gliptin?ExenInsulinCostsMixtures:HumanversusanaloguesNoevidenceofdifference,?IncreasedriskofHypoglycaemia.90%oftype2patientsdoaswelloncheaperhumanmixtureSAVINGS:100patientsaround£15/month/patient=£20000peryearInsulinCostsMixtures:InsulinsandCostsNighttimeinsulin:NPH-noevidenceofdifferenceincontrol,weightgain,?Increasedhypoglycaemia£20permonthdifference:100patients£24,000perannumInsulinsandCostsNighttimeiAmberyPetal.PosterpresentedatDiabetesUKannualprofessionalconference,2005.P120.Approximately60%ofMonotherapyPatientsareMissingGlycaemicTargetsHbA1c<7%HbA1c710%HbA1c>10%40%7%53%AmberyPetal.PosterpresentAimsWhatistheidealHbA1c?LegacyeffectBloodPressure:canwegotoolow?Cholesteroltargets,andtheroleofFibratesWhoshouldhaveaspirin?CaseScenariosWhatdrugstouseaftermetformin?Whentouseinsulinandwhichone?Anythingelse?AimsWhatistheidealHbA1c?LWhatistheidealHbA1cUKPDSdataDCCTandEDICtrialADVANCEACCORDSTENOVADT

WhatistheidealHbA1cUKPDSdHbA1c

cross-sectional,medianvaluesHbA1ccross-sectional,median糖尿病研究最新进展(2011年)课件UKPDS80–LegacyofLong-termGlycaemicControl(30YearFollowUpData)UKPDS80–LegacyofLong-termAftermedian8.5yearspost-trialfollow-up

AggregateEndpoint

1997

2007Anydiabetesrelatedendpoint RRR:

12%

9%

P:

0.029

0.040

Microvasculardisease RRR:

25%

24%

P:

0.0099

0.001Myocardialinfarction RRR: 16% 15%

P:

0.052

0.014All-causemortality RRR: 6% 13%

P:

0.44

0.007RRR=RelativeRiskReduction,P=LogRankLegacyEffectofEarlierGlucoseControlAftermedian8.5yearspost-trACCORDADVANCEandVADT-NoSignificantEffectonMacroVascularOutcomesACCORDADVANCEVADTNo.ofparticipants10,25111,1401791Participantage,years626660Durationofdiabetesatstudyentry,years10811.5HbA1CatBaseline,%8.17.59.4Participantswithpriorcardiovascularevent,%353240Durationoffollow-up,years3.45.06ACCORDADVANCEandVADT-NoSiSummaryofACCORD,ADVANCEandVADT:Outcomes,intensivevs.standardACCORDADVANCEVADTHbA1c,%6.4vs.7.5*6.5vs.7.3*6.9vs.8.4*Deathfromanycause,%

5.0vs.4.0*8.9vs.9.6NADeathfromcardiovascularevent,%

2.6vs.1.8*4.5vs.5.22.1vs.1.7NonfatalMI,%

3.6vs.4.6*2.7vs.2.86.1vs.6.3Nonfatalstroke,%

1.3vs.1.23.8vs.3.82.0vs.3.1Neworworseningnephropathy,%

NA4.1vs.5.2*NAMajor/severehypoglycemia,%

10.5vs.3.5*2.7vs.1.5*21.1vs.9.7*Weightgain,kg3.5vs.0.4*0.0vs.-1.0*NA*p≤0.05

SummaryofACCORD,ADVANCEand糖尿病研究最新进展(2011年)课件ACCORDRetinalConclusionIntensiveglycemiccontrolandintensivecombinationtreatmentofdyslipidemia,butnotintensiveblood-pressurecontrol,reducedtherateofprogressionofdiabeticretinopathy.(FundedbytheNationalHeart,Lung,andBloodInstituteandothers;ClinicalTnumbers,NCT00000620fortheACCORDstudyandNCT00542178fortheACCORDEyestudy.)‏ACCORDRetinalConclusionIntenADVANCE4.3yearsoffollow-up:Perindopril/indapamideBloodpressurereduced7.1±0.3mmHgsystolicand2.9±0.2mmHgdiastolic(P<0.001).135/75:140/77(baseline145/81)HbA1Cwasreducedby0.61±0.02%after4.3years(P<0.001).GlicazideMRADVANCE4.3yearsoffollow-up:糖尿病研究最新进展(2011年)课件VADTConclusionIntensiveglucosecontrolinpatientswithpoorlycontrolledtype2diabeteshadnosignificanteffectontheratesofmajorcardiovascularevents,death,ormicrovascularcomplications,withtheexceptionofprogressionofalbuminuria(P=0.01)VADTConclusionIntensiveglucoVADTintheContextofthe“NaturalHistory”ofType2DiabetesTime(yearssincediagnosis)HbA1c(%)6.06.57.07.58.08.59.09.512345678910111213141516DrivetheriskforcomplicationsVADTintheContextofthe“NaMeanSystolicBlood-PressureLevelsatEachStudyVisitTheACCORDStudyGroup.NEnglJMed2010;362:1575-1585MeanSystolicBlood-PressureLACCORDBPConclusionInpatientswithtype2diabetesathighriskforcardiovascularevents,targetingasystolicbloodpressureoflessthan120mmHg,ascomparedwithlessthan140mmHg,didnotreducetherateofacompositeoutcomeoffatalandnonfatalmajorcardiovasculareventsACCORDBPConclusionInpatientACCORDlipidConclusionThecombinationoffenofibrateandsimvastatindidnotreducetherateoffatalcardiovascularevents,nonfatalmyocardialinfarction,ornonfatalstroke,ascomparedwithsimvastatinaloneTheseresultsdonotsupporttheroutineuseofcombinationtherapywithfenofibrateandsimvastatintoreducecardiovascularriskinthemajorityofhigh-riskpatientswithtype2diabetesACCORDlipidConclusionThecomHazardRatiosforthePrimaryOutcomeinPrespecifiedSubgroupsTheACCORDStudyGroup.NEnglJMed2010;362:1563-1574HazardRatiosforthePrimary糖尿病研究最新进展(2011年)课件DiabetesandAspirinGuidanceYesinsecondarypreventionPrimarypreventionshouldbeonanindividualbasiswithconsiderationofthebenefitsandharmsofaspirin,takingintoaccountthepresenceofriskfactorsforvasculardisease(includingconditionssuchasdiabetes)andtheriskofgastrointestinalbleeding..MHRADrugSafetyUpdate.October2009.DiabetesandAspirinGuidanceYDiabetesandAspirinGuidancePrimaryprevention:over50,smoker,treatedforhypertensionandhighcholesterol:yesUnder50withallfactorsandFH:yesfromage40Under50:noOver50non-smokeronlyDM:noOver50treatedforhypertension,andhighcholesterol:probablyyesDiabetesandAspirinGuidancePAspirinandDiabetesTheASCENDStudyisalargemultisitestudyrecruiting10,000patientsover40withtype2diabetesdesignedtoanswerthequestionwhetheraspirinshouldbeprescribedroutinelyindiabeticpatients.(2011)ACCEPT-DItalianstudy5000patients,greaterthan50.(aspirin/placebo)2007startedAspirinandDiabetesTheASCENDNICEGuidelines:GeneralRecommendations

Structureddiabeteseducation,andaimforgoodglucosecontrolearlyoninthediagnosis(metforminearly).TargetHbA1cof6.5%forType2Diabetesingeneral,butavoidpursuinghighlyintensivemanagementoflevelslessthan7%inthosewithlimitedlifeexpectancy5years),especiallyifusingdrugswhichcangeneratehypoglycaemiaBloodpressuretargetoflessthan140/80mmHg(Nolegacyeffect)Simvastatin40mgorequivalentforallpatientswithType2diabetesagedover40,irrespectiveofexperienceofCVdisease.NICEGuidelines:GeneralRecomMonotherapywith1stor2ndGenerationSUswasAssociatedwith24-61%ExcessRiskForAllCauseMortalityComparedwithMetforminMonotherapy(P<0.001)2.01.51.00.51stGenerationsulphonylureasvmetformin2ndGenerationsulphonylureasvmetforminAllrosiglitazone*vmetforminAllpioglitazone*vmetforminAllrosiglitazone*vallpioglitazone*Othercombinations†vmetforminTzoulakietal.,BMJ2009;339:b4731HazardRatio(95%CI)(LogScale)*Anytherapy(monotherapyandcombinations).†OtherdrugsandcombinationsofanyoralantidiabetesdrugsexcludingrosiglitazoneandpioglitazoneModel2resultsMonotherapywith1stor2ndGeACCORD:MortalityHRforIndividualAgents1ACCORDStudyGroup.EffectsofIntensiveGlucoseLoweringinType2Diabetes.NEnglJMed2008;358:2545-592.ACCORDWebcastpresentedattheAmericanDiabetesAssociation,6-10June2008.Availableat:/StoreTemplate/default.aspx?ReturnUrl=%2fDefault.aspx5.Cefalu,WT.NEnglJMed2008;358(24):2633-2635.6.AvandiaSPCMarch2008ACCORD:MortalityHRforIndivA40yearoldSupermarketWorkerA40yearoldladyhasa2yearhistoryoftype2diabetes.Herglycaemiccontrolisconsistentlypoor.Sheisanex-smokerwithaBMIof49.Hercurren

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