Physicians' Academy for Cardiovascular Education

Professor I W Campbell

Slides (presentation) - Jan. 20, 2010

ASIA–EUROPEEXPERTDIALOGUEONDIABETESANDVASCULARPROTECTIONPhysicians’AcademyforCardiovascularEducation“GuidelinesandADA/EASDconsensusstatement:howtoimplement”ProfessorIWCampbellButeMedicalSchoolUniversityofSt.Andrews
Choice of agents in current use
ADA-EASDConsensusAlgorithmforT2DM
DiabetesCare2009;32:1-11
Bedtime Insulin Plus Oral Agents
Effects of Addition of Oral Agents or Morning Insulin to Bedtime Insulin Regimen in Type 2 Diabetes
Lessons from UKPDS: Legacy Effect of Earlier Metformin Therapy
TreatmentmonotherapyfailureintheUKPDS
ADA:EASD Consensus Algorithm
SUMMARYOFTZDCONCLUSIONSMONOTHERAPY:decreaseinHbA1cof0.5-1.4%Appeartohavemoredurableeffectonglycaemiccontrol,esp.vsSUConcernsreweightgain,oedema,twofoldincreaseinCCFReductioninvisceralfatinsomestudiesBeneficial(Pio-)effectorneutral(Rosi-)onatherogeniclipidprofilesSeveralmeta-analyseshavesuggested30-40%RRincreaseinMIwithRosi-.PROactive:NosignificanteffectsofPio-vsplaceboonprimaryCVDoutcomePROactive:Pio-associatedwith16%decreasedeath,MI,stroke-acontroversialsecondaryend-pointwithmarginalstatisticalsignificance.
SUMMARYOFTZDCONCLUSIONSMeta-analyseshavesupportedapossiblebeneficialeffectofpio-onCVDriskCautionwithTZDsrefluidretention/CCFIncreasedriskfractureinfemales,?malesUNANIMOUSDECISIONOFCONSENSUSGROUPAGAINSTUSEOFROSIGLITAZONE
In these new guidelines
HbA1c before and after addition of sulfonylurea to metformin
SULFONYLUREASANDHYPOGLYCAEMIAUKHypoglycaemiaStudyGroup7%type2DMpatientsexperienceaseverehypoglycaemiaepisodeperyear(Diabetologia2007;50:1140–1147)LesserdegreesofSIHmorefrequent.38.7%ofsubjectsonglibenclamideinADOPTstudy(2006)
EffectsoforalantidiabeticdrugsonHbA1candhypoglycemiceventsinfourlarge,randomised,double-blindstudies(Quartet)
PossiblemechanismofactionandbeneficialeffectsofTZDsonβ-cellfunction
Durabilityofglycaemiccontrolwithsulfonylureas
HBA1c=glycatedhaemoglobinA1c;Hanefeld=;Tan=;UKPDS=UKprospectivediabetesstudy;Chicago=carotidintima-mediathicknessinatherosclerosisusingpioglitazone;ADOPT=adiabetesoutcomeprogressiontrial;PERISCOPE=pioglitazoneeffectonregressionofintravascularsonographiccoronaryobstructionprospectiveevaluationCampbellI.BrJDiabetesVascDis2009;9:53–63.
Long-term Durable Reduction in HbA1c with the Addition of Pioglitazone to Metformin and SU
PROactive study: time to permanent insulin use
Prevention of weight gain in metformin combination
Changes in dyslipidaemic profile with TZDs
Meanchangeincarotidintima-mediathickness
Primary endpoint: change in atheroma volume (%)
EffectofpioglitazoneonrecurrentMIinpatientswithpreviousMI
Effect of pioglitazone on recurrent stroke in patients with previous stroke
Risk of death, myocardial infarction, or stroke with pioglitazone versus control
Hazard ratios for cardiovascular events with glitazones
HomePDetalLancet2009;373:2125-35
HomePDetalLancet2009;373:2125-35
Pioglitazone’s effect on mortality after a serious HF event
Study Objective
Study Design
Results
Results 1st and 2nd Generation SUs
Results Thiazolidinediones (TZDs)
Authors summary and conclusion
Sitagliptin with metformin showed comparable efficacy to sulphonylurea with metformin
Sitagliptin with metformin had a low risk of weight gain and low incidence of hypoglycaemia
Exenatide(Byetta):TheAMIGOStudies
Exenatide versus insulin glargine in patients with type 2 diabetes
HbA1c change over 26 weeks All subjects
Subjects achieving HbA1c targets All subjects
Body weight change from baseline Subjects receiving metformin
Frequency of nausea All subjects
GlycaemictargetsandInsulinInjections
DistributionofHbA1cValuesat3Years
Increase in Body Weight Over 3 Years
Grade 2 or 3 Hypoglycaemia Over 3 Years
Summary
Doesdiabetestherapyinfluencetheriskofcancer?
Increasedcancer-relatedmortalityforpatientswithtype2diabeteswhousesulfonylureasorinsulinSLBowker,SRMajumdar,PVeugelers,JAJohnson
New users of metformin are at low risk of incident cancer
Retrospective analysis of patients with early stage breast cancer 1990-2007 receiving neoadjuvant therapy

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