American Association of Clinical Endocrinologists’ Comprehensive Diabetes Management Algorithm 2013

1. ENDOCRINE PRACTICE Vol 19 No. 2 March/April 2013 327
George Grunberger, MD, FACP, FACE
Yehuda Handelsman, MD, FACP, FACE, FNLA
Irl B. Hirsch, MD
Paul S. Jellinger, MD, MACE
Janet B. McGill, MD, FACE
Jeffrey I. Mechanick, MD, FACE, ECNU, FACN, FACP
Paul D. Rosenblit, MD, FACE
Guillermo Umpierrez, MD, FACE
Michael H. Davidson, MD, Advisor
Martin J. Abrahamson, MD
Joshua I. Barzilay, MD, FACE
Lawrence Blonde, MD, FACP, FACE
Zachary T. Bloomgarden, MD, MACE
Michael A. Bush, MD
Samuel Dagogo-Jack, MD, FACE
Michael B. Davidson, DO, FACE
Daniel Einhorn, MD, FACP, FACE
W. Timothy Garvey, MD
TASK FORCE
Alan J. Garber, MD, PhD, FACE, Chair
AACE COMPREHENSIVE
DIABETES MANAGEMENT
ALGORITHM
2013
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Copyright © 2013 AACE.

2. 328 AACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2013;19(No. 2)
TABLE of CONTENTS
Comprehensive Diabetes
Algorithm
Complications-Centric
Model for Care of the
Overweight/Obese Patient
Prediabetes Algorithm
Goals of Glycemic Control
Algorithm for
Adding/Intensifying Insulin
CVD Risk Factor
Modifications Algorithm
Profiles of Antidiabetic
Medications
Principles for Treatment
of Type 2 Diabetes
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3. AACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2013;19(No. 2) 329
CARDIOMETABOLICDISEASEBIOMECHANICALCOMPLICATIONS
STEP1EVALUATIONFORCOMPLICATIONSANDSTAGING
STEP3Iftherapeutictargetsforimprovementsincomplicationsnotmet,intensifylifestyleand/ormedical
and/orsurgicaltreatmentmodalitiesforgreaterweightloss
BMI≥27WITHCOMPLICATIONS
StageSeverityofComplications
LOWMEDIUMHIGH
STEP2
(i)Therapeutictargetsforimprovementincomplications,
(ii)Treatmentmodalityand
(iii)Treatmentintensityforweightlossbasedonstaging
SELECT:
MD/RDcounseling;web/remoteprogram;structuredmultidisciplinaryprogramLifestyleModification:
phentermine;orlistat;lorcaserin;phentermine/topiramateERMedicalTherapy:
Lapband;gastricsleeve;gastricbypassSurgicalTherapy(BMI≥35):
Complications-CentricModelforCare
oftheOverweight/ObesePatient
NOCOMPLICATIONS
BMI25–26.9,
orBMI≥27
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4. 330 AACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2013;19(No. 2)
Proceedto
Hyperglycemia
Algorithm
LIFESTYLEMODIFICATION
(IncludingMedicallyAssistedWeightLoss)
OTHERCVD
RISKFACTORS
TZD
GLP-1RA
NORMAL
GLYCEMIA
OVERT
DIABETES
Ifglycemianotnormalized,
considerwithcaution
ANTIHYPERGLYCEMICTHERAPIES
FPG>100|2hourPG>140
HypertensionDyslipidemia
LowRisk
Medications
Metformin
Acarbose
CVDRiskFactor
ModificationsAlgorithm
ANTI-OBESITY
THERAPIES
Intensify
Anti-
Obesity
Efforts
1Pre-DM
Criterion
MultiplePre-DM
Criteria
PrediabetesAlgorithm
IFG(100–125)|IGT(140–199)|METABOLICSYNDROME(NCEP2005)
Progression
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5. AACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2013;19(No. 2) 331
A1c≤6.5%
Forhealthypatients
withoutconcurrent
illnessandatlow
hypoglycemicrisk
A1c>6.5%
Individualizegoals
forpatientswith
concurrentillness
andatriskfor
hypoglycemia
GoalsforGlycemicControl
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6. 332 AACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2013;19(No. 2)
MONOTHERAPY*
IfA1c>6.5%
in3monthsadd
seconddrug
(DualTherapy)
INSULIN
±OTHER
AGENTS
ENTRYA1c<7.5%ENTRYA1c≥7.5%ENTRYA1c>9.0%
ADDORINTENSIFYINSULIN
NOSYMPTOMSSYMPTOMS
OR
DUAL
THERAPY
TRIPLE
THERAPY
PROGRESSIONOFDISEASE
GlycemicControlAlgorithm
*Orderofmedicationslistedareasuggestedhierarchyofusage
**Baseduponphase3clinicaltrialsdata=Usewithcaution
Fewadverseevents
orpossiblebenefits
=
LEGEND
Metformin
GLP-1RA
DPP4-i
AG-i
SGLT-2**
TZD
SU/GLN
DUALTHERAPY*
Ifnotatgoalin3
monthsproceed
totripletherapy
GLP-1RA
DPP4-i
TZD
**SGLT-2
Basalinsulin
Colesevelam
BromocriptineQR
AG-i
SU/GLN
MET
orother
first-line
agent
TRIPLETHERAPY*
Ifnotatgoalin3
monthsproceed
toorintensify
insulintherapy
GLP-1RA
TZD
**SGLT-2
Basalinsulin
DPP4-i
Colesevelam
BromocriptineQR
AG-i
SU/GLN
MET
orother
first-line
agent
2ND LINE AGENT
LIFESTYLEMODIFICATION
(IncludingMedicallyAssistedWeightLoss)
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7. AACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2013;19(No. 2) 333
TDD
0.1–0.2U/kg
TDD
0.2–0.3U/kg
**GlycemicGoal:
•FormostpatientswithT2D,anA1c<7%,fastingand
premealBG<110mg/dLintheabsenceofhypoglycemia.
•A1candFBGtargetsmaybeadjustedbasedonpatient’s
age,durationofdiabetes,presenceofcomorbidities,
diabeticcomplications,andhypoglycemiarisk.
Considerdiscontinuingorreducingsulfonylureaafter
basalinsulinstarted(basalanalogspreferredtoNPH)
AddPrandialInsulin
Insulintitrationevery2–3daysto
reachglycemicgoal:
•Fixedregimen:IncreaseTDDby2U
•Adjustableregimen:
•FBG>180mg/dL:add4U
•FBG140–180mg/dL:add2U
•FBG110–139mg/dL:add1U
•Ifhypoglycemia,reduceTDDby:
•BG<70mg/dL:10%–20%
•BG<40mg/dL:20%–40%
INTENSIFY(prandialcontrol)
Insulintitrationevery2–3daystoreachglycemicgoal:
•IncreasebasalTDDasfollows:
•Fixedregimen:IncreaseTDDby2U
•Adjustableregimen:
•FBG>180mg/dL:add4U
•FBG140–180mg/dL:add2U
•FBG100–139mg/dL:add1U
•Increaseprandialdoseby10%foranymealifthe2-hr
postprandialornextpremealglucoseis>180mg/dL
•Premixed:IncreaseTDDby10%iffasting/premeal
BG>180mg/dL
•IffastingAMhypoglycemia,reducebasalinsulin
•Ifnighttimehypoglycemia,reducebasaland/orpre-supper
orpre-eveningsnackshort/rapid-actinginsulin
•Ifbetweenmealdaytimehypoglycemia,reduceprevious
premealshort/rapid-actinginsulin
TDD:0.3-0.5U/kg
50%BasalAnalog
50%PrandialAnalog
Lessdesirable:NPH
andregularinsulinor
premixedinsulinGlycemicControl
NotatGoal**
AddGLP-1RA
orDPP4-i
AlgorithmforAdding/IntensifyingInsulin
A1c<8%A1c>8%
STARTBASAL(long-actinginsulin)
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8. 334 AACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2013;19(No. 2)
LIPIDPANEL:AssessCVDRisk
DYSLIPIDEMIA
Ifstatin-intolerant
Intensifytherapiesto
attaingoalsaccording
torisklevels
StatinTherapy
IfTG>500mg/dL,fibrates,
omega-3ethylesters,niacin
Tryalternatestatin,lower
statindoseorfrequency,
oraddnonstatinLDL-C-
loweringtherapies
Repeatlipidpanel;
assessadequacy,
toleranceoftherapy
Assessadequacy&toleranceoftherapywithfocusedlaboratoryevaluationsandpatientfollow-up
HYPERTENSION
RISKLEVELSMODERATEHIGH
DESIRABLELEVELSDESIRABLELEVELS
LDL-C(mg/dL)<100<70
Non-HDL-C(mg/dL)<130<100
TG(mg/dL)<150<150
TC/HDL-C<3.5<3.0
ApoB(mg/dL)<90<80
LDL-P(nmol/L)<1200<1000
DMbutnoother
majorriskand/orage<40
DM+majorCVDrisk(s)(HTN,FamHx,
lowHDL-C,smoking)orCVD*
IntensifyTLC(weightloss,physicalactivity,dietarychanges)
andglycemiccontrol;Consideradditionaltherapy
Ifnotatdesirablelevels:
TolowerLDL-C:Intensifystatin,addezetimibe&/orcolesevelam&/orniacin
TolowerNon-HDL-C,TG:Intensifystatin&/oraddOM3EE&/orfibrates&/orniacin
TolowerApoB,LDL-P:Intensifystatin&/orezetimibe&/orcolesevelam&/orniacin
Ifnotatgoal(2–3months)
Addß-blockerorcalciumchannel
blockerorthiazidediuretic
Addnextagentfromtheabove
group,repeat
Ifnotatgoal(2–3months)
Ifnotatgoal(2–3months)
Additionalchoices(α-blockers,
centralagents,vasodilators,
spironolactone)
Achievementoftargetblood
pressureiscritical
GOAL:SYSTOLIC~130,
DIASTOLIC~80mmHg
Forinitialblood
pressure
>150/100mmHg:
Dualtherapy
Thiazide
Calcium
Channel
Blocker
ß-blocker
ACEi
or
ARB
ACEi
or
ARB
*evenmoreintensivetherapymightbewarranted
THERAPEUTICLIFESTYLECHANGES(SeeObesityAlgorithm)
CVDRiskFactorModificationsAlgorithm
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9. AACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2013;19(No. 2) 335
ProfilesofAntidiabeticMedications
METDPP-4iGLP-1RATZDAGICOLSVLBCR-QRINSULINSGLT-2PRAML
HYPONeutralNeutralNeutralNeutralNeutralNeutralNeutral
Moderate
toSevere
NeutralNeutral
WEIGHT
Slight
Loss
NeutralLossGainNeutralNeutralNeutralGainGainLossLoss
RENAL/
GU
Contra-
indicated
Stage
3B,4,5
Dose
Adjustment
Maybe
Necessary
(Except
Linagliptin)
Exenatide
Contra-
indicated
CrCl<30
May
Worsen
Fluid
Retention
NeutralNeutralNeutral
More
Hypo
Risk
More
HypoRisk
&Fluid
Retention
InfectionsNeutral
GISxModerateNeutralModerateNeutralModerateMildModerateNeutralNeutralNeutralModerate
CHFNeutral
NeutralNeutral
Moderate
NeutralNeutral
NeutralNeutral
NeutralNeutralNeutral
CVDBenefitNeutralSafe?
BONENeutralNeutralNeutral
Moderate
Bone
Loss
NeutralNeutralNeutralNeutralNeutral
?
BoneLoss
Neutral
GLN
SU
Moderate/
Severe
Mild
FewadverseeventsorpossiblebenefitsUsewithcautionLikelihoodofadverseeffects
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10. 336 AACE Comprehensive Diabetes Management Algorithm, Endocr Pract. 2013;19(No. 2)
PrinciplesoftheAACEAlgorithm
fortheTreatmentofType2Diabetes
1)Lifestyleoptimizationisessentialforallpa-
tientswithdiabetes.Thisismultifaceted,
ongoing,andengagestheentirediabetes
team.However,sucheffortsshouldnotdelay
neededpharmacotherapy,whichcanbeiniti-
atedsimultaneouslyandadjustedbasedon
theresponsetolifestyleefforts.Theneedfor
medicaltherapyshouldnotbeinterpretedas
afailureoflifestylemanagement,butasan
adjuncttoit.
2)TheA1ctargetmustbeindividualized,based
onnumerousfactors,suchasage,co-morbid
conditions,durationofdiabetes,riskofhypo-
glycemia,patientmotivation,adherence,life
expectancy,etc.AnA1cof6.5%orlessisstill
consideredoptimalifitcanbeachievedina
safeandaffordablemanner,buthighertar-
getsmaybeappropriateandmaychangeina
givenindividualovertime.
3)Glycemiccontroltargetsincludefastingand
postprandialglucoseasdeterminedbyself
bloodglucosemonitoring.
4)Thechoiceoftherapiesmustbeindividualized
basedonattributesofthepatient(asabove)
andthemedicationsthemselves(seeProfiles
ofAnti-DiabeticMedications).Attributesof
medicationsthataffecttheirchoiceinclude:
riskofinducinghypoglycemia,riskofweight
gain,easeofuse,cost,andsafetyimpactof
kidney,heart,orliverdisease.Thisalgorithm
includeseveryFDA-approvedclassofmedica-
tionsfordiabetes.Thisalgorithmalsostratifies
choiceoftherapiesbasedoninitialA1c.
5)Minimizingriskofhypoglycemiaisapriority.
Itisamatterofsafety,adherence,andcost.
6)Minimizingriskofweightgainisapriority.It
tooisamatterofsafety,adherence,andcost.
7)Thealgorithmprovidesguidancetowhat
therapiestoinitiateandadd,butrespectsin-
dividualcircumstancesthatwouldmakedif-
ferentchoices.
8)Therapieswithcomplementarymechanisms
ofactionmusttypicallybeusedincombina-
tionsforoptimumglycemiccontrol.
9)Effectivenessoftherapymustbeevaluated
frequentlyuntilstable(e.g.every3months)
usingmultiplecriteriaincludingA1c,SMBG
recordsincludingbothfastingandpost-pran-
dialdata,documentedandsuspectedhypo-
glycemia,andmonitoringforotherpotential
adverseevents(weightgain,fluidretention,
hepatic,renal,orcardiacdisease),andmoni-
toringofco-morbidities,relevantlaboratory
data,concomitantdrugadministration,dia-
beticcomplications,andpsycho-socialfactors
affectingpatientcare.
10)Safetyandefficacyshouldbegivenhigher
prioritiesthaninitialacquisitioncostof
medicationspersesincecostofmedica-
tionsisonlyasmallpartofthetotalcostof
careofdiabetes.Indeterminingthecostof
amedication,considerationshouldbegiven
tomonitoringrequirements,riskofhypogly-
cemiaandweightgain,etc.
11)Thealgorithmshouldbeassimpleaspossible
togainphysicianacceptanceandimproveits
utilityandusabilityinclinicalpractice.
12)Thealgorithmshouldservetohelpeducate
theclinicianaswellastoguidetherapyatthe
pointofcare.
13)Thealgorithmshouldconform,asnearlyas
possible,toaconsensusforcurrentstandard
ofpracticeofcarebyexpertendocrinologists
whospecializeinthemanagementofpatients
withtype2diabetesandhavethebroadest
experienceinoutpatientclinicalpractice.
14)Thealgorithmshouldbeasspecificaspos-
sible,andprovideguidancetothephysician
withprioritizationandarationaleforselec-
tionofanyparticularregimen.
15)Rapid-actinginsulinanalogsaresuperiorto
Regularbecausetheyaremorepredictable.
16)Long-actinginsulinanalogsaresuperiorto
NPHinsulinbecausetheyprovideafairlyflat
responseforapproximately24hoursandpro-
videbetterreproducibilityandconsistency
bothbetweensubjectsandwithinsubjects,
withacorrespondingreductionintheriskof
hypoglycemia.
Thisdocumentrepresentstheofficialposi-
tionoftheAmericanAssociationofClinical
EndocrinologistsandtheAmericanCol-
legeofEndocrinology.Wheretherewere
noRCTsorspecificFDAlabelingforis-
suesinclinicalpractice,theparticipating
clinicalexpertsutilizedtheirjudgment
andexperience.Everyeffortwasmadeto
achieveconsensusamongthecommittee
members.Manydetailsthatcouldnotbe
includedinthegraphicsummary(Figure)
aredescribedinthetext.
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