Management of Hyperglycemia in Type 2

Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach
Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)
Writing Group
American Diabetes Association European Assoc. for the Study of Diabetes Richard M. Bergenstal MD
Intl Diabetes Center, Minneapolis, MN
Michaela Dia#ant MD, PhD

'U University, A!ster$a!, he Netherlan$s
John B. Buse MD, PhD Anne L. Peters MD Richard Wender MD Silvio E. Inzucchi MD co!chair"
%ale University, Ne& Haven, C
Ele $errannini MD Michael %auc& MD A'ostolos (sa'as MD, PhD David R. Matthe)s MD, DPhil co!chair"
-.for$ University, -.for$, U/
University of North Carolina, Chapel Hill, NC University of #isa, #isa, Italy
Univ. of Southern California, Los Angeles, Diabetes(entru!, CA )a$ Lauterberg, *er!any
ho!as "efferson University, #hila$elphia, #A Aristotle University, hessaloni+i, *ree,e
ADA-EASD Position Statement: Management of Hyperglycemia in T2DM: A Patient-Centered Approach
1. PATIENT !ENTE"ED APP"#A!$ %. &A!'G"#(ND

Epidemio)ogy and hea)th care impact "e)ationship of g)ycemic contro) to outcomes #*er*ie+ of the pathogenesis of Type % diabetes
,. ANTI $-PE"G.-!E/I! T$E"AP G)ycemic targets Therapeutic options

.ifesty)e #ra) agents 0 non insu)in in1ectab)es Insu)in
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
ADA-EASD Position Statement: Management of Hyperglycemia in T2DM: A Patient-Centered Approach
,. ANTI$-PE"G.-!E/I! T$E"AP Imp)ementation Strategies

Initia) drug therapy Ad*ancing to dua) combination therapy Ad*ancing to trip)e combination therapy Transitions to and titrations of insu)in
2. #T$E" !#NSIDE"ATI#NS
Age
Weight Se34racia)4ethnic4genetic differences !omorbidities (Coronary artery disease, Heart failure,

Chronic kidney disease, Liver dysfunction, Hypoglycemia)
5. 6(T("E DI"E!TI#NS Diabetes 4 "ESEA"!$ NEEDS Care, Diabetologia. 19 April 2012 [Epub ahead of print]
ADA-EASD Position Statement: Management of Hyperglycemia in T2DM
1. Patient !entered Approach

0...provi$ing ,are that is respe,tful of an$ responsive to in$ivi$ual patient preferen,es, nee$s, an$ values 1 ensuring that patient values gui$e all ,lini,al $e,isions.2 Gauge patient7s preferred )e*e) of in*o)*ement.
E3p)ore8 +here possib)e8 therapeutic

choices.
(ti)i9e decision aids. Shared decision ma:ing ; fina) decisions re<

)ifesty)e choices u)timate)y )ies +ith the Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
%. &A!'G"#(ND
Epidemio)ogy and hea)th care impact
Age ad1usted Percentage of (.S. Adu)ts +ith #besity or Diagnosed Diabetes Obesity (BMI 30 kg/m )
2
# # & & E E S S II T T Diabetes
1994
2000
2009
No Data
<14.0%
14.0-17.9%
18.0-21.9%
22.0-25.9%
>26.0%
D D II A A & & E E T T E E S S
1994
2000
2009
No Data
<4.5%
4.5-5.9%
6.0-7.4%
7.5-8.9%
>9.0%
CDCs Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics
The Diabetes Epidemic< G)oba) Pro1ections8 %=1=;%=,=
IDF. Diabetes Atlas 5th Ed. 2011
%. &A!'G"#(ND
"e)ationship of g)ycemic contro)
to outcomes
Impact of Intensi*e Therapy for Diabetes< Summary of /a1or !)inica) Tria)s

Study
*+PDS D,,( EDI,. ACC-3D AD'ANC4 'AD
/icro*as c
!>D
/orta)ity
Initia) Tria) .ong Term 6o))o+ up . in (/DM
%. &A!'G"#(ND
#*er*ie+ of the pathogenesis of

T%D/
! Insu)in secretory dysfunction !Insu)in resistance ?musc)e8 fat8 )i*er@ !Increased endogenous g)ucose production !Deranged adipocyte bio)ogy !Decreased incretin effect
n Pathophysio)ogica) Defects in T%D

incretin e33ect 'ancreatic insulin secretion
'ancreatic glucagon secretion
gut car0oh1drate deliver1 2 a0sor'tion
H!PE"#$!CEM%A
he'atic glucose 'roduction
Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011

'eri'heral glucose u'ta&e
,. ANTI $-PE"G.-!E/I! T$E"AP-
G)ycemic targets
! ! ! !
$bA1c B C.=D #ean P4 /56!/76 #g-dl 89.:!9.; ##ol-l<" Pre!'randial P4 =/:6 #g-dl >.? ##ol-l" Post!'randial P4 =/96 #g-dl /6.6 ##ol-l" Indi*idua)i9ation is &e1@
(ighter targets 7.6 ! 7.5A" ! 1ounger,
healthier Looser targets >.5 ! 9.6AB" ! older, co#or0idities, h1'ogl1ce#ia 'rone, etc.
P4 C 'las#a glucose
6igure 1
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print] (Adapted with permission from: Ismail-Beigi F, et al. Ann Intern Med 2011;154:554)
Therapeutic options< .ifesty)e

!Weight optimi9ation !$ea)thy diet
! Increased acti*ity )e*e)

Therapeutic options< Oral agents & non-insulin injecta le
! Meglitinides ! Met3or#in ! Sul3on1lureas ! -glucosidase ! (hiazolidinediones inhi0itors ! DPP!D inhi0itors ! Bile acid seEuestrants ! 4LP!/ rece'tor agonists ! Do'a#ine!? agonists ! A#1lin #i#etics
!)ass
&iguanid es
/echanism
Activates AMP! &inase Fe'atic glucose 'roduction ,loses +A(P channels Insulin secretion PPAR! activator insulin sensitivit1
Ad*antages
EGtensive eG'erience %o h1'ogl1ce#ia Weight neutral H ,ID EGtensive eG'erience Microvasc. ris&
Disad*antages !ost
4astrointestinal Lactic acidosis B!/? de3icienc1 ,ontraindications F1'ogl1ce#ia Weight gain Lo) dura0ilit1 H Ische#ic 'reconditioning Weight gain Ede#a - heart 3ailure Bone 3ractures H MI rosi" H Bladder ca 'io" Lo)
S(s 4 /eg)itini des
Lo)
TEDs
%o h1'ogl1ce#ia Dura0ilit1 (4s, FDL!, H ,ID 'io"
Figh
Inhi0its %o h1'ogl1ce#ia 4astrointestinal Mod. %ons1ste#ic Dosing glucosidase 3reEuenc1 Post!'randial Slo)s Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print] 1. Properties of anti hyperg)ycemic Modest A/c car0oh1drate glucose agents GIs
!)ass
DPP 2 inhibitors G.P 1 receptor agonists
/echanism
Inhi0its DPP!D Increases 4LP!/, 4IP Activates 4LP!/ R Insulin, glucagon gastric e#'t1ing satiet1 Activates a#1lin rece'tor glucagon gastric e#'t1ing satiet1
Ad*antages
%o h1'ogl1ce#ia Well tolerated Weight loss %o h1'ogl1ce#ia H Beta cell #ass H ,I 'rotection
Disad*antag !ost es
Modest A/c H Pancreatitis *rticaria 4I H Pancreatitis Medullar1 ca InJecta0le Figh
Figh
Amy)in mimetics
Weight loss PP4
4I Modest A/c InJecta0le F1'o )insulin Dosing 3reEuenc1
Figh
&i)e acid seFuestr ants
Bind 0ile acids Fe'atic glucose 'roduction
1. Properties of anti hyperg)ycemic agents
%o h1'ogl1ce#ia 4I Figh %ons1ste#ic Modest A/c Post!'randial Dosing glucose 3reEuenc1 ,ID events Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
!)ass
Insu)in
/echanism
Activates insulin rece'tor 'eri'heral glucose u'ta&e
Ad*antages Disad*antage !ost s

*niversall1 e33ective *nli#ited e33icac1 Microvascular ris& F1'ogl1ce#ia Weight gain H Mitogenicit1 InJecta0le (raining reEuire#ents KStig#aL Iaria0l e
Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print] 1. Properties of anti hyperg)ycemic agents
Therapeutic options< Insu)in

Neutra) protamine $agedorn ?NP$@ "egu)ar &asa) ana)ogues ?g)argine8 detemir@ "apid ana)ogues ?)ispro8 aspart8 g)u)isine@ Pre mi3ed *arieties
Therapeutic options< Insu)in

Insu)in )e*e) Ra i! (Lis ro" #s art" $%&%isine) ()ort (Reg&%ar) Interme!iate (*+') Long (Detemir) Long ($%argine) 6 ?D ? D 7 9 /6 /? /D /7 $ours after in1ection
'o&rs
/9
?6
??
Imp)ementation strategies<
!Initia) therapy !Ad*ancing to dua) combination therapy !Ad*ancing to trip)e combination therapy !Transitions to 0 titrations of insu)in
Antihyperg)ycemic Therapy< Genera) "ecommendations [Epub ahead of print]
Diabetes Care, Diabetologia. 19 April 2012
Fuentia) Insu)in Strategies in T%D/
Age Weight Se3 4 racia) 4 ethnic 4 genetic differences !omorbidities
!!oronary artery disease !$eart 6ai)ure !!hronic :idney disease !.i*er dysfunction !$ypog)ycemia
Age< #)der adu)ts
!Reduced li3e eG'ectanc1 !Figher ,ID 0urden !Reduced 4$R !At ris& 3or adverse events 3ro# 'ol1'har#ac1 !More li&el1 to 0e co#'ro#ised 3ro# h1'ogl1ce#ia
.ess .ess ambitious ambitious targets targets $bA1c $bA1c BC.5;G.=D BC.5;G.=D if tighter not tighter targets targets not easi)y easi)y achie*ed achie*ed 6ocus safety 6ocus on drug drug safety Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Weight
!MaJorit1 o3 (?DM 'atients over)eight - o0ese !Intensive li3est1le 'rogra# !Met3or#in !4LP!/ rece'tor agonists !H Bariatric surger1 !,onsider LADA in lean 'atients
Anti hyperg)ycemic Therapy< Genera) "ecommendations [Epub ahead of print]
d "ecommendations< When Goa) is to A*oid Weight [Epub Gain ahead of print]
Se34ethnic4racia)4genetic differences
!Little is &no)n !MMDN 2 other #onogenic 3or#s o3 dia0etes !Latinos@ #ore insulin resistance !East Asians@ #ore 0eta cell d1s3unction !4ender #a1 drive concerns a0out adverse e33ects e.g., 0one loss 3ro# (ODs"
!omorbidities
!!oronary Disease *+PDS" *+PDS" Avoid Avoid h1'ogl1ce#ia h1'ogl1ce#ia !$eart 6ai)ure H H S*s S*s 2 2 ische#ic ische#ic !"ena) disease 'reconditioning 'reconditioning !.i*er dysfunction H H Pioglitazone Pioglitazone 2 2 ,ID ,ID events events !$ypog)ycemia H H E33ects E33ects o3 o3 incretin!0ased incretin!0ased thera'ies thera'ies
Met3or#in@ Met3or#in@ ,ID ,ID 0ene3it 0ene3it
!omorbidities
!!oronary Disease Met3or#in@ Met3or#in@ Ma1 Ma1 use use unless !$eart 6ai)ure unless condition condition is is unsta0le unsta0le or severe or severe !"ena) disease Avoid Avoid (ODs (ODs !.i*er dysfunction H H E33ects E33ects o3 o3 incretin!0ased incretin!0ased thera'ies !$ypog)ycemia thera'ies
!omorbidities
!!oronary Disease !$eart 6ai)ure !"ena) disease h1'ogl1ce#ia h1'ogl1ce#ia Met3or#in Met3or#in 2 2 lactic lactic acidosis acidosis !.i*er dysfunction *S@ *S@ sto' sto' PS,r PS,r Q Q /.5 /.5 /.D /.D !$ypog)ycemia )o#en" )o#en" *+@ *+@ dose dose P4$R P4$R =D5 =D5 2 2 sto' sto' P4$R P4$R =:6 =:6 ,aution ,aution )ith )ith S*s S*s es'. es'. gl10uride" gl10uride" DPP!D!iRs S 3or Diabetes Care, Diabetologia. 19 April adJust 2012 [Epub ahead of print] DPP!D!iRs S dose dose adJust 3or
Increased Increased ris& ris& o3 o3
!omorbidities
!!oronary Disease !$eart 6ai)ure !"ena) disease !.i*er dysfunction advanced advanced liver liver disease disease Pioglitazone Pioglitazone #a1 #a1 hel' hel' !$ypog)ycemia steatosis steatosis Insulin Insulin 0est 0est o'tion o'tion i3 i3 disease disease severe severe
Most Most drugs drugs not not tested tested in in
!omorbidities
!!oronary Disease !$eart 6ai)ure !"ena) disease !.i*er dysfunction !$ypog)ycemia
E#erging E#erging concerns concerns
regarding regarding association association )ith )ith increased #ortalit1 increased #ortalit1 Pro'er Pro'er drug drug selection selection in in the h1'ogl1ce#ia the h1'ogl1ce#ia 'rone 'rone
Anti hyperg)ycemic Therapy< Genera) "ecommendations [Epub ahead of print]
d "ecommendations< When Goa) is to A*oid $ypog)ycemia [Epub ahead of print]
ed "ecommendations< When Goa) is to /inimi9e !osts [Epub ahead of print]
Guide)ines for G)ycemic8 &P8 0 .ipid !ontro) #meri,an Diabetes #sso,- $oa%s
$bA1! Preprandia) g)ucose Postprandia) g)ucose &)ood pressure
B C.=D 5in$ivi$uali(ation6 C= 1,= #g-dL :.;!>.? ##ol-l" B 1G= #g-dL B 1,=4G= ##Fg .D.< B 1== #g-dL ?.5; ##ol-l" B C= #g-dL /.9/ ##ol-l" )ith overt ,ID" $D.< H 2= #g-dL /.6D ##ol-l" H 5= #g-dL /.:6 ##ol-l" TG< B 15= #g-dL /.7; ##ol-l"
ADA. Diabetes Care. 2012;35:S11-63
.ipids
HDL = i! -densit" #i$o$rotein% LDL = #o&-densit" #i$o$rotein% '( = $#as)a !#*cose% +( = tri!#"cerides.
2. 6(T("E DI"E!TI#NS 4 "ESEA"!$ NEEDS
!omparati*e effecti*eness research

$ocus on i#'ortant clinical outco#es
!ontributions of genomic research Perpetua) need for c)inica) 1udgmentI
&E! P'%(TS 4l1ce#ic targets 2 B4!lo)ering thera'ies #ust 0e individualized.
Diet, eGercise, 2 education@ 3oundation o3 an1 (?DM thera'1 'rogra# *nless contraindicated, #et3or#in C o'ti#al /st! line drug. A3ter #et3or#in, data are li#ited. ,o#0ination thera'1 )ith /!? other oral - inJecta0le agents is reasona0leT #ini#ize side e33ects. *lti#atel1, #an1 'atients )ill reEuire insulin thera'1 alone - in co#0ination )ith other agents to #aintain B4 control. Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]
Invited Reviewers
James Best, The University of Melbourne, AU Henk Bilo, Isala Clinics, Zwolle, NL John Boltri, Wayne State University, Detroit, MI Thomas Buchanan, Univ of So California, LA, CA Paul Callaway, University of Kansas,Wichita, KS Bernard Charbonnel, University of Nantes, France Stephen Colagiuri, The University of Sydney, AS Samuel Dagogo-Jack, Univ of Tenn, Memphis, TN Margo Farber, Detroit Medical Center, Detroit, MI Cynthia Fritschi, University of Illinois, Chicago, IL Rowan Hillson, Hillingdon Hospital, Uxbridge, U.K. Faramarz Ismail-Beigi, CWR Univ, Cleveland, OH Devan Kansagara, Oregon H&S Univ, Portland, OR Ilias Migdalis, NIMTS Hospital, Athens, Greece Donna Miller, Univ of So California, LA, CA Robert Ratner, MedStar/Georgetown Univ, DC Julio Rosenstock, Dallas Diab/Endo Ctr, Dallas, TX Guntram Schernthaner, Rudolfstiftung Hosp, Vienna, AT Robert Sherwin, Yale University, New Haven, CT Jay Skyler, University of Miami, Miami, FL Geralyn Spollett, Yale University,New Haven, CT Ellie Strock, Intl Diabetes Center, Minneapolis, MN Agathocles Tsatsoulis, University of Ioannina, GR Andrew Wolf, Univ of Virginia Charlottesville, VA Bernard Zinman, University of Toronto, CA
Professional Practice Committee, American Diabetes Association Panel for Overseeing Guidelines and Statements, European Association for the Study of Diabetes American Association of Diabetes Educators The Endocrine Society American College of Physicians

Management of Hyperglycemia in Type 2

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Management of Hyperglycemia in Type 2

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Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach

Michaela Dia#ant MD, PhD

University of North Carolina, Chapel Hill, NC University of #isa, #isa, Italy

Univ. of Southern California, Los Angeles, Diabetes(entru!, CA )a$ Lauterberg, *er!any

ho!as "efferson University, #hila$elphia, #A Aristotle University, hessaloni+i, *ree,e

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM: A Patient-Centered Approach

1. PATIENT !ENTE"ED APP"#A!$ %. &A!'G"#(ND

,. ANTI $-PE"G.-!E/I! T$E"AP G)ycemic targets Therapeutic options

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM: A Patient-Centered Approach

,. ANTI$-PE"G.-!E/I! T$E"AP Imp)ementation Strategies

Weight Se34racia)4ethnic4genetic differences !omorbidities (Coronary artery disease, Heart failure,

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

1. Patient !entered Approach

E3p)ore8 +here possib)e8 therapeutic

(ti)i9e decision aids. Shared decision ma:ing ; fina) decisions re<

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

# # & & E E S S II T T Diabetes

The Diabetes Epidemic< G)oba) Pro1ections8 %=1=;%=,=

IDF. Diabetes Atlas 5th Ed. 2011

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

Impact of Intensi*e Therapy for Diabetes< Summary of /a1or !)inica) Tria)s

Initia) Tria) .ong Term 6o))o+ up . in (/DM

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

#*er*ie+ of the pathogenesis of

n Pathophysio)ogica) Defects in T%D

gut car0oh1drate deliver1 2 a0sor'tion

he'atic glucose 'roduction

Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

,. ANTI $-PE"G.-!E/I! T$E"AP-

(ighter targets 7.6 ! 7.5A" ! 1ounger,

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

,. ANTI $-PE"G.-!E/I! T$E"AP-

Therapeutic options< .ifesty)e

! Increased acti*ity )e*e)

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

,. ANTI $-PE"G.-!E/I! T$E"AP-

Therapeutic options< Oral agents & non-insulin injecta le

S(s 4 /eg)itini des

%o h1'ogl1ce#ia Dura0ilit1 (4s, FDL!, H ,ID 'io"

Weight loss PP4

4I Modest A/c InJecta0le F1'o )insulin Dosing 3reEuenc1

&i)e acid seFuestr ants

Bind 0ile acids Fe'atic glucose 'roduction

1. Properties of anti hyperg)ycemic agents

Ad*antages Disad*antage !ost s

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

,. ANTI $-PE"G.-!E/I! T$E"AP-

Therapeutic options< Insu)in

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

,. ANTI $-PE"G.-!E/I! T$E"AP-

Therapeutic options< Insu)in

ADA-EASD Position Statement: Management of Hyperglycemia in T2DM

,. ANTI $-PE"G.-!E/I! T$E"AP-

Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

Antihyperg)ycemic Therapy< Genera) "ecommendations [Epub ahead of print]

Diabetes Care, Diabetologia. 19 April 2012

Antihyperg)ycemic Therapy< Genera) "ecommendations [Epub ahead of print]

Diabetes Care, Diabetologia. 19 April 2012

Antihyperg)ycemic Therapy< Genera) "ecommendations [Epub ahead of print]

#erie+ of the pathogenesis of

! Increased actiity )ee)

Adantages Disadantage !ost s

!omparatie effectieness research