acp insulin slidecast 222

8/9/2019 ACP Insulin SlideCAST 222

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Please Take A Moment to Complete the Pre-Program ClinicalPerformance and Knowledge Gap Assessment Survey


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ndividuali!ing nsulinTherapy in

Type " #ia$etesAligning Speci%c nsulin &ormulations withSpeci%c #ia$etic Patients' Pro%les' and Clinical

Parameters

A (oad Map for Clinical Success

VIVIAN A. FONSECA, MD, FRCP- Program ChairProfessor of Medicine and Pharmacology ) Tullis Tulane AlumniChair in #ia$etes ) Chief' Section of *ndocrinology ) Tulane

+niversity ,ealth Sciences Center ) Past President' Science andMedicine ) American #ia$etes Association


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CM*-certi%ed symposium ointly sponsored $y the+niversity of MassachusettsMedical School and

CM*ducation (esources' ..C

Commercial Support/ ThisCM* activity is supported $y

an educational grant fromsano%-aventis +0S0 nc0' ASA12& C2MPA13

4elcome and Program2verview4elcome and Program2verview


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#istinguished &aculty

VIVIAN A. FONSECA, MD,FRCP Program ChairProfessor of Medicine andPharmacology ) Tullis TulaneAlumni Chair in #ia$etes )

Chief' Section of*ndocrinology ) Tulane+niversity ,ealth SciencesCenter ) Past President'Science and Medicine )

American #ia$etesAssociation

CHARLES F. SHAEFER JR.,MD, FACP

Assistant Clinical Professor ofMedicine Medical Colle e of

LUIGI F. MENEGHINI, MD,MBAProfessor ) #epartment ofnternal Medicine ) #ivision of*ndocrinology ) +niversity of

Te5as Southwestern MedicalCenter ) #allas' Te5as

JUAN P. FRIAS, MD, FACEClinical Assistant Professor of

Medicine ) +niversity ofCalifornia ) San #iego'California ) Chief Medical 26cer) 1ational (esearch nstitute ).os Angeles' CA


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C2 #isclosures

Fac!"# M$m%$r R$!a"io&'hi( Cor(ora"io&)Ma&*ac"r$r

Viia& Fo&'$ca, MD

(esearch Support 8to

Tulane9/

,onoraria for Consultingand .ectures/

Grants from *li .illy' A$$ott' (eata'Asahi

Gla5o Smith Kline' Takeda' 1ovo1ordisk'sano%-aventis' *li .illy' Pamla$s'

Astra-:eneca' A$$ott' ;ristol-MyersS


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*volving' Multimodal Approachesfor 2ptimi!ing ,A?c Target GoalAttainment

and Clinical 2utcomes in T"#

The &oundation (ole of nsulin Therapy as Part of anntegrated Treatment (oadmap for Primary Care-;ased Management


VIVIAN A. FONSECA, MD, FRCP- Program ChairProfessor of Medicine and Pharmacology ) Tullis Tulane AlumniChair in #ia$etes ) Chief' Section of *ndocrinology ) Tulane



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Antihyperglycaemic Therapy in T"#M - A#AGuidelines "@?"Healthy eating, weight control, increased physical activity

Efficacy (

HbA1c)…

Hypoglycaemia……

Weight…………

……

Side

effects………

!osts……………

…

"nitial dr#g

monotherapy

$etformin % $etformin % $etformin % $etformin % $etformin %

&wo'dr#g

combinations

"f combination therapy that incl#des basal ins#lin did not achieve HbA1c target after '

months, proceed to a more comple* ins#lin strategy #s#ally in combination with one or two

non'ins#lin agents$ore comple*

ins#lin

strategies "ns#lin (m#ltiple daily doses)

"f individ#alised HbA1c target not reached, proceed to two'dr#g combination

"f individ#alised HbA1c target not reached, proceed to three'dr#g combination

S+

High$oderate ris

-ain

Hypoglycemia

.ow

&/0

High.ow ris

-ain

Edema, H,

fract

High

0223i

"ntermediate.ow ris

.oss

-"

High

-.21'4A

"ntermediate.ow ris

.oss

-"

High

"ns#lin

"ntermediate.ow ris

.oss

-"

High

S+%

&/0or 0223i

or -.21'4A

or "ns#lin

&/0%

S+or 0223i

or -.21'4A

or "ns#lin

0223i%

S+or &/0

or "ns#lin

-.21'4A%

S+or &/0

or "ns#lin

"ns#lin%

&/0or 0223i

or -.21'4A

Efficacy (

HbA1c)…

Hypoglycaemia…

…

Weight……………

…

Side

effects…………

!osts………………

…

"n5#cchi SE, et al Diabetes Care 6 Diabetologia, 17 April 8918 :Ep#b ahead of print;

$etforminHigh

.ow ris


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.ong-Term ;ene%ts of GlycemicControlfor Microvascular Complications

.ong-term $ene%ts persist after intervention● Type ? 8*#C9/ ntensive treatment reduces risk of

microvascular complications for at least years$eyond therapy

●

Type " 8+KP#S9/ Tight glycemic control reduces risk ofmicrovascular eBectseven ?@ years after treatment

.ong-term $ene%ts not seen consistently● 1o reduction of microvascular complicationsD in

Eeterans ABairs #ia$etes Trial 8EA#T9 intensive arm(esults suggest a Fmeta$olic memory8Flegacy9 eBect

r co&$r'io& *rom &ormo- "o micro- or macroa!%mi&ria

0$mio!og# o* Dia%$"$' I&"$r$&"io&' a&0 Com(!ica"io&'1&i"$0 2i&g0om Pro'($c"i$ Dia%$"$' S"0#

al0 Diabetes Care0 "@@HI"J8"9/L@-LL0et al0 N Engl J Med0 "@@IJ8?9/?NN-?J0 for #CCT>*#C (esearch Group0 JAMA0 "@@I"J@8?H9/"?J-"?HN0

et al0 Diabetologia. "@@JI"8N9/?"?JO?""H

i


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in Type " #ia$etes Mellitus

Progressive nature of the -celldysfunction in type " dia$etes mellitusimportant cause of secondary failure oforal therapy

&or some patients' it=s the only therapy thatwill get $lood glucose to target

Proven eBective

Can $e continually titrated

+sually well accepted $y patients/

Small needles and insulin pens

& enthusiastically recommended $y health

care provider


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?+K Prospective #ia$etes Study 8+KP#S9 Group0 Lancet 0 ?JJI"/L-H0",olman ((' et al0 N Engl J Med0 "@@IJ/?NN-?J0 The #ia$etes Control and Complications Trial (esearch Group0N Engl J Med. ?JJI"JIJNN-JH0 L1athan #M' et al0 N Engl J Med0 "@@I/"HL-"H0

Gerstein ,C' et al0 N Engl J Med. "@@I/"L-"J0 HPatel A' et al0 N Engl J Med. "@@I/"H@-"N"0N#uckworth 4' et al0 N Engl J Med. "@@JIH@/?"J-?J0

Study Microvascular CVD Mortality

UKPDS1,2

DCCT/EDIC3.4

Action to ControlCardiovascular Ris inDia!"t"s #ACC$RD%&

'ot availa!l"

AD(A'CE)

("t"rans A**airs Dia!"t"s Trial#(ADT%+

on-t"r *ollo0uInitial trial

mpact of ntensive Glycemic TherapySummary of Maor Clinical Trials


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.4 #.+&.4% 5 #51) to 3%

Kelly TN, et al. Ann Intern Med. E-pub ahead of print.

In t6" ov"rall anal7sis, int"nsiv" -lucos" control 6ad no si-ni*icant "**"ct on "it6"r8C( ortalit7 #r"lativ" ris .+ 9&: CI, .+)1.24;%orallcaus" ortalit7 #r"lativ" ris . 9&: CI, .41.1&;%

Pool"d anal7sis o* t6" UKPDS, ACC$RD, AD(A'CE, and (ADT trials 7i"ld"d a 1): ov"rall r"duction in

non*atal


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ACC2(# *ye/ Microvascular (elative(isk (eduction 4ith ntensive Therapy

#uration of follow-up

L years

;aseline A?C

Mean nt/ 0"Q?0@R

Mean Std/ 0Q?0@R

A?C at ?yeara

Median nt/ H0LRa

Median Std/ N0Ra

(etinopathy

(ate of progression of dia$etic retinopathy/

ntensive/ N0RStandard/ ?@0LR8P@0@@9

aSigni%cant $etween-group diBerence was maintained throughout the study

ACC2(#Action to Control Cardiovascular (isk in #ia$etes

ACC2(# *ye Glycemia Arm

ACCORD S"0# Gro( a&0 ACCORD E#$ S"0# Gro(. N Engl J Med .-


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0el 2rato S, et al. Int J Clin Pract 8919>3?87@93

6.5

6.0

7.0

7.5

8.0

9.5

9.0

8.5

1 2 3 4 5 6 7 8 109 1211 1413 15 1716

Time since diagnosis 8years9

B$*or$ $&"$ri&g VAD9

i&"$&'i$ "r$a"m$&" arm

A*"$r $&"$ri&g VAD9

i&"$&'i$ "r$a"m$&" arm

, $ A ? c

8 R 9

Generation of a$ad glycemiclegacy=

#rives risk ofcomplications

Mo0$!!i&g "h$ (rior

hi'"or# o* (a"i$&"'r$cri"$0 i& VAD9i!!'"ra"$' "h$0ra%ac3' o* !a"$i&"$r$&"io&

Solid line/ changes in ,$A?c in response to intensive treatment in EA#T

+pper $roken line/ theoretical reconstruction of prior dia$etes progression $ased on +KP#S

.ower $roken line/ the ideal time course of glycemic control

.egacy of ;ad Meta$olicMemory=


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mplications of ACC2(#'A#EA1C*' and EA#T forMicrovascular (isk

Microvascular disease .owering A?C to U N0@R reduces

microvascular and neuropathic

complications in type " dia$etes f achieva$le without causing signi%cant

hypoglycemia or other adverse events'even lower A?C goals may $e suggested for

selected individuals having/● Short duration of dia$etes● .ong life e5pectancy●

1o signi%cant CE#S&yler +S et al. Diabetes Care. !$$!*/#"-/!.


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mplications of ACC2(#' A#EA1C*'and EA#T for Macrovascular (isk

Macrovascular disease ntensive glycemic control that e5ceeds an A?C

goal of V N0@R yields no signi%cant reduction inCE# outcomes compared to standard glycemiccontrol

.owering A?C to a goal of .;7 is areasona$le glycemic goal until more evidence$ecomes availa$le

.ong-term follow-up of the #CCT and +KP#Scohorts suggests that treating to an A?C goal$elow or near N0@R yields long-term reductionsin the risk of macrovascular disease if it isinstituted in the years soon after diagnosis of

dia$etesS3#!$r JS $" a!. Diabetes Care. :;;51=:?


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+KP#S/ ntensive nsulin>S+ Therapy(educes (isk of 2utcomes in 1ewly-

#iagnosed T"#M

a& RR, et al . N Engl J Med :;;1=65?:; >6< >>

5>=


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.ong-term *Bects of ntensive Glucosein 1ewly #iagnosed T"#M patients

HR (95%CI)HR (95%CI)

ntensive 8S+>ns9 vs. Conventional glucose control

HR (95%CI) HR (95%CI)

ntensive 8metformin9 vs. Conventional glucose control

Holman RR, et al . N Engl J Med 2008;358:2545–59.


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ULN / (($r !imi" o* &orma! 4>.:78righ" A, $" a!. Diabetes Care. :;;:1:6?==;-==>.

M $ a & A < C

;7

67

>7

7

7

57

$ar' *rom Ra&0omia"io&

; < : = @ 6 >

Co&$&"io&a! (o!ic#I&'!i& a!o&$

S!*o!r$a i&'!i&

.>

.<

>.>P/;.;;

*arly Addition of nsulin Signi%cantlymproves Meta$olic Control 8+KP#S N9

ULN

Cli i l ti i ( t


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Clinical nertia in (esponse tonade


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Time to nsulin nitiation andncidence of Complications are ncreasing

2o'"$ 2, et al . Diabetologia :;


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C(*#T/ nsulin is Started .ate and inPatients with a ,igh Prevalence of CE#isease and (isk &actors

,$A?c at ;aseline

All pts V0R0O

?@0?RW?@0?R

n '@? ?'@" JH JN"

HbA1c (B) J0 N0H J0 ??0N

$acrovasc#lar disease (B) L H

Hypertension (B) HJ N? HJ HH.0. C19 mg=d. ?? N ?? ?

&- C 1@9 mg=d. LN L LN ?

Dbesity ($" C9 Fg=mG) L? L" L@ L@

Worldwd! r!"#$r% on n#&ln n$a$on n '2() and *ollow &+

reemantle @(S#ppl1)?A3I3

G t .ik lih d f A hi i


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4iddle $!, et al Diabetes 8997>@(S#ppl1)?A18@

Greater .ikelihood of Achieving ,$A?c VNR when ;aseline is

.owerPooled analysis of "?J patients with"L weeks titrated glargine added to 2A#


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Greater .ikelihood of Achieving ,$A?c VNR when ;aseline is

.ower

,$A?c change from $aseline at ? year R attaining V NR ,$A?c at ? year

aseline HbA1c

@ to JI

aseline HbA1c

@ I to J to J7 K7

Aagren $, et al Diabetologia 8911>@3(S#ppl1)?198I88.3- n#&ln "lar"n! or d!$!mr 0.7- /o$h, 11- H n#&ln

@ to JI@ I to J to J7 K7

Analysis of electronic medical records of ?'LJL people

with T"#M initiating insulinD $etween "@@ and "@?@

Gl i Ch ith li


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Glycemic Changes with nsulinGlargine$y ;aseline 2A# +se

7 I 71 I

H b A 1 c

onseca L, et al Diabetes Obes Metab 8911>1?1388

I1 I9 7 I1 I9

$ean HbA1cat baseline

$ean HbA1cat 83 wees

9=1 DA0 8 DA0s $E& only S+ only $E& % S+

p M 9999

p M 9917

@3I @8I 1N @93 @3HbA1c JIB

(B patients)O 2ooled analysis

N p M 99991 vs all taing S+


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on#!a , et al . Diabetes Obes Metab 2011;13:814–22.

9=1

DA0

8

DA0

p M 99188

$et

only

S+

only

$E&

% S+

1o signi%cant diBerence in$ody weight

! o n f i r m e d h y p o g l y c e m

i a

( B p

t s

w i t h E - J @ 9 m g

= d . )

,ypoglycemia and 4eight with nsulinGlargine$y ;aseline 2A# +se/ Pooled Analysis

p M 9999

Signi%cantly lower hypoglycemiain M*T only patients

9=1

DA0

8

DA0

$et

only

S+

only

$E&

% S+ ! h a n g e i n b o

d y w e i g h t ( g )

p M 97@3I p M 919

i ; d 4 i ht Aft


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ncrease in ;ody 4eight After Treatment Correlates with ;aseline,$A?cPooled data from J (CTs 8"L weeks9 in adults with T"#M treated

with insulin glargine or comparator 8HR other insulins' "R 2A#s'HR dietary9

!ah% , et al . Diabetes 2011;60S&++l.1:2308.

C h a & g $ i &

% o 0 # $ i g h "

4 3 g 8

J K7 K7

Com(ara"or, r / ;.:@


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Comparator' r -@0?""' p V @0@@?

nsulin glargine' r -@0?H' p V @0@@?

C h a & g $ i & % o 0 # $ i g h "

4 3 g 8

6; K>6

Ba'$!i&$ ag$ 4#$ar'8

K6; "o >6

*Bect of Age and $;seline,$A?c on ;ody 4eight Change

L$ah# JL, et al . Diabetes :;


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ntensive nsulin Therapy in 1ew2nset T"#M

" patients with newlydiagnosed type " #M

CS' M#' or 2,A untilreversal ofhyperglycemia0 Treat for" weeks

(emission de%ned as&;G W ?"H mg>d. or"-hr PP W ?@ mg>d.

nitial ,$A?c J0R-J0R

$&g J, et al . Lancet :;;1=


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Y-cell &unction After ntensivensulin Therapy in 1ew 2nset T"#M

p < 99991

!S"" in the remission gro#p

$0" in the remission gro#p

DHA in the remission gro#p

. p e r m i n

9

Weng P, et al Lancet 899>I1?1I@9

*

* p < 99@ vs each intervention in the

remssion gro#p (after treatment)

p = 999

*B t f li Gl i


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*Bect of nsulin Glargine on Y-cell &unction

2ennart5 !, et al Diabetes Care 8911>3?893@

&irst-phase insulin response Second-phase insulin response

&irst-phase 8t @ to ?@ min minus $asal levels9 and second-phase insulin

secretion8t ?@ to ?"@ min minus $asal levels9 in response to E glucose administration

in T"#M 8n ?L9 $efore and after weeks of insulin glargine treatment

∆ n

s u l i n S e c r e t i o n

8 m

+ > k g p e r m i n 9

∆ n s

u l i n S e c r e t i o n

8 m +

> k g p e r m i n 9 8@

89

1@

19

9@

99

;eforeglargine

After weeksof glargine

1318

19

9

9

99

9398

;eforeglargine

After weeksof glargine

p M 999I1 p M 993

Short term ntensive Therapy in


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Short-term ntensive Therapy in1ewly #iagnosed T"#M mprovesY-cell &unction

No&-r$mi''io&

R$mi''io&

B$*or$"h$ra(#

A*"$r"h$ra(#

A" <#$ar

I & A I R i & '

4 I U ) m ! 8

NG9

IG9

Q

;

;


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The (ole of nsulin-;asedManagement within The

&ramework of A#A>*AS#Guidelines for Type " #ia$etes

A Patient-Centered Approach ;ased onndividuali!ing and ntegrating nsulin 4ithin aMultimodal Treatment Plan


VIVIAN A. FONSECA, MD, FRCP - Program ChairProfessor of Medicine and Pharmacology ) Tullis Tulane AlumniChair in #ia$etes ) Chief' Section of *ndocrinology ) Tulane


;arriers to nsulin Therapy


33/197

Most physicians● Prefer to delay insulin until a$solutely

necessary● Admit they use insulin as a threat with

patients

Most patients● ;elieve that needing insulin means they

failed to follow treatment

recommendations

;arriers to nsulin Therapynitiation Attitudes in the #A41 Study

DAN / Dia%$"$' A""i"0$', i'h$', a&0 N$$0'

2or#"3o'3i M. Int J Obes. :;;:1:>4'((! =8?S=-:>5.

Sr$# o* :>< Ph#'icia&' a&0 :;>< Pa"i$&"'


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nsulin &acts

Strength +?@@ 8?@@ units per m.9 O +@@availa$le and others in trials

Eials and syringes/

Eials ?@ m. 8?@@@ units9 - new ml hospital

vials0 Syringes 8@0' @0' ?0@ m.9I "-? gaugeI >?H

or ?>" inch needles0

Eials are good for ? month after opening

Pens m. 8@@ units9

1eedles >?H'>?H'

?>" inch' "J-? gauge'8FnanoL mm and " gauge9

*5piration time after opening varies $yroduct

The [uest for a ;etter ;asal nsulin


35/197

2$# Fac"or' A''$''i&g I&'!i&S"ra"$gi$'

A$solute A?c reductionZ

R Achieving target

VNRZ nsulin titration and

dosesZ

Amount of

nsulin nitiation and 2ptimi!ation in Type " #M

The [uest for a ;etter ;asal nsulin\

Addition of ;asal nsulin vs a Third


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Addition of ;asal nsulin vs a Third2ral Agent to Com$ination 2ral

Therapy

P;.;6 *or g!argi&$ ' ro'ig!i"ao&$

Ro'$&'"oc3 J, $" a!. Diabetes Care.

:;;>1:5?66@-665.

:@; @ .67

A ? C

Time 8weeks9

G!argi&$Ro'ig!i"ao&$

;aseline A?C

;

7 7 57


37/197

Addition of ;asal nsulin to 2ral Therapy Treat-to-Target Trial

6> Pa"i$&"' i"h 9#($ : Dia%$"$' o& < or : Ora! Ag$&"'

PG / (!a'ma g!co'$

Ri00!$ MC, $" a!. Diabetes Care. :;;=1:>?=;;-

=;>

NPH

G!argi&$

5.;7

.6

7.;

7

.67

.;7

>.67

>.;7

A ? C

; @ <:

<>

:;

:@ C u m u l a t i v e 1 u m $ e r o

f * v e n t s

8 # o c u m

e n t e d P G U H

m g > d . 9

4eeks of Treatment Time 8days9

5;;

;;

>;;

6;;

=;;


38/197

, y

p o g l y c a e m

i a

NPH

G!argi&$

A?c

T ;.@;.>7

The impact of hypoglycaemia on A?c

The [uest for a ;etter ;asal nsulin\

A F[uali%ed A?c $y,ypoglycaemia

nsulin Analogues Are Associated 4ith


39/197

nsulin Analogues Are Associated 4ith.ower ,ypoglycemia (ates Than ,umannsulin in T?#M

a

.S received $edtime 1P, and prandial 1P,I (, received1P, at $edtime only0 ?0 Mullins P' et al0Clin Ther 0 "@@NI"J/?H@N-?H?J0"0 .alli C' et al0 Diabetes Care0 ?JJJI""/LH-LNN0

.;.6.;

A.6>.;6.6

;

:

@

Fr$V$&c

#o*Mi!0H#(o

g! #c$mia,

$(i'o0$')(a"i$&"-mo&"h


40/197

Minimi!ing ,ypoglycemia in Treatment(egimens Containing nsulin for Patients with

T"#M

a Most fre


41/197

nsulin Analogues May 2Bset the (isk of,ypoglycemia 2ften 2$served 4ith nsulinnitiation in T"#M

nsulin doses' T##/ $asal' J +I twice-daily' @ +I prandial' H

+0a P V 0@ within group0 Pontiroli A*' et al0 Diabetes Obes Metab0 "@?"I?L/L-LLH0

n contrast with other studies' this meta-analysis found that adding 2A#s toinsulin regimens increased the risk of nocturnal hypoglycemia despite lowerinsulin T##'$ut some included trials allowed S+s

a

a a

A & a

! o g $ i & ' ! i & % $ " " $

r

H m a &

i & '

! i & % $ " " $ r

Severe ,ypoglycemia ncreases the


42/197

Severe ,ypoglycemia ncreases the(isk of Mortality in Patients 4ith

T"#M and CE#

nad$!d ra$!#; da$a #hownar! haard ra$o#.

1. Bond# (, !$ al. BMJ. 2010;340:/4909.2. 'h! = 'ral =n?!#$"a$or#. Eur Heart J . 2013 S!+ 2. @+&/ ah!ad o* +rn$A.

Macrovascular events ?0NN 8?0J-"0"9I P V 0@@?

#eathany cause"0@ 8?0H-"09I P V 0@@?

#eatharrhythmia"0?L 8?0L-0?9I P V 0@@?

#eathCE cause"0@" 8?0"-"0HJ9I P V 0@@?

2(G1"

ACC2(#?#eathany cause'standard therapy group"0J 8?0H-L0H9

#eathany cause'intensive therapy group?0NJ 8?0"-"0LL9


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Com%i&i&g I&'!i& 9h$ra(#i"h M$"*ormi& Mi&imi$'

$igh" Gai& 3ki-]^rvinen? Avil_s-Santa" ;ergenstal

nsulin

nsulin `Metformi

nnsuli

nnsulin `

Metforminnsuli

n

nsulin `Metform

in

Nm%$r o*

S%$c"'"L ?J "" "? "" "@

Dra"io& o*S"0#4mo&"h'8

?" ?" H H L L

I&'!i&Do'ag$ a"

E&0 4U)0a#8

"L H ?"@ J" ?H JJ

A3I(s#ppl 1)?A7 Abstract 3I

P C 0.01

nsulin Therapy


44/197

;asal treatment● Controls glucose production $etween meals

and overnight●

1early constant levelsPrandial treatment

● .imits hyperglycemia after meals● mmediate rise and sharp peak at ? hour

postmeal

&or ideal insulin replacement therapy' eachcomponent should come from a diBerent

insulin

nsulin TherapyArguments for ;asal and Prandial 2ptions

(elative Changes over 3ears and


45/197

(elative Changes over 3ears and,ypoglycaemiaMean±1D

Tailoring nsulin Therapy to Meet


46/197

Tailoring nsulin Therapy to MeetPatient Goals and .ifestyle

nsulin regimen should $eadusted to meals and activitylevel' not vice versa

● ;asal insulin dose adusted toprovide ade


47/197

;asal nsulin The Simple 4ay to Add nsulin

nitiate insulin with a single inection of a $asal insulin'

such as insulin glargine

;edtime or morning long-actinginsulin 2(

;edtime intermediate-acting insulin

#aily dose/ ?@ + or @0" +>kg

ncrease dose $y " + every daysuntil &;G is 0JON0" mmol>. 8N@O?@mg>d.9

f &;G is W?@ mmol>. 8W?@ mg>d.9'

increase dose $y L + every days

Continue regimen andcheck ,$A?c every months

n the event ofhypoglycaemia or &;Glevel V0J mmol>. 8VN@mg>d.9' reduce $edtimeinsulin dose $y XL units'

or $y ?@R if WH@ units

FBG / Fa'"i&g %!oo0 g!co'$

Ch$c3 FBG 0ai!#

Na"ha& DM, et al . Diabetes Care

nsulin #osages 8units>kg9


48/197

1 4iddle $!, et al Diabetes Care 899>8(11)?99'9

8 -erstein H!, et al Diabetic Med 899>8(I)?I'I38

Qi'PRrvinen H, et al Diabetologia 899>37()?338'3@13 Qi'PRrvinen H, et al Diabetes Care 899I>9()?13'17

S"0#9r$a" "o

9arg$"<INSIGH9: LANME9= INI9IA9E@

&inal

doses@0L +>kg 8Glar9

@0L" +>kg 81P,9

@0L? +>kg8Glar9

@0HJ +>kg8Glar9

@0HH +>kg81P,9

@0H@ to @0HL+>kg 8Glar9

nsulin #osages 8units>kg9from Pu$lished Studies

Stepwise nsulin nitiation in


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OAD'

Ba'a!i&'!i& WOAD'

< %o!'W %a'a!i&'!i& WOAD'

:%o!'$'W %a'a!i&'!i& WOAD'

=%o!'$'

W %a'a!i&'!i& WOAD'

Stepwise nsulin nitiation in T"#M

$eas#re A0A=EAS01

AA!E=A!E8

"0

asal algorithms

"nitial dose 19 +=d A1! J B? 91'98 +=gA1! C B? 98'9 +=g


50/197

2verview of Stepwise ;asal and Prandialnsulin8Sw;;T9 Trials in T"#M

S!! /aF o* +ro"ram /ooF *or #$&d% d!#"n# and E1 $ar"!$#.a P C .01 ?# on$rol "ro&+; / P C .05 ?# on$rol "ro&+.

1. Raah (, !$ al. Diabetes Metab. 2012;38:507D514.

2. )!n!"hn , !$ al. End!r Pra!t. 2011;17:727D736.3. Ro#!n#$oF , !$ al. Diabetes. 2011;60#&++l 1:E20 @a/#$ra$ 73D


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Stepwise nsulin nitiation (esults in .ess,ypoglycemia Than nitial ;;T

H%+o"l%!ma, #%m+$om# w$h +rom+$ r!o?!r% a*$!r admn#$ra$on o*oral ar/oh%dra$!; #!?!r! h%+o"l%!ma, #%m+$oma$ w$h a###$an!

n!!d!d and B> C 36 m"Gd or +rom+$ r!o?!r% w$h oral ar/oh%dra$!,= "l&o#!, or "l&a"on.

1. Raah (, !$ al. Diabetes Metab. 2012;38:507D514.

2. )!n!"hn , !$ al. End!r Pra!t. 2011;17:727D746.

3. www.lnal$ral#."o?. '00384085.4. Rod/ard HW, !$ al. Diabetes. 2013;62#&++l 1:E66 @a/#$ra$ 256D


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nsulin nitiation and Titration in T"#MPearls for Practice

Stepwise insulin initiation and titration areassociated with improved control with low ratesof severe hypoglycemia

,owever' fewer than @R of patients with

T"#M treated with any insulin ` oralantidia$etic regimen attain A?C V NR

Consider discontinuing insulin secretagogueswhen prandial insulin is initiated

Performing H- or N-point SM;G for days $eforemedical appointments provides usefulinformation for glycemic pattern management in

T"#M

*ven more fre uent lucose monitorin 8e '

nsulin Pen +sage ;y


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g yGeographical (egion

(24 rest of world0

Clarke A et al0 E!pert Opin Dr"g Deliv 0 "@@NIL/?H-?NL.

Period' mo>y

n

s u l i n + n i t s

#

e l i v e r e d $ y n s u l i n

P e n s v s A l l 2

t h e r

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? > " @ @

? @ > " @ @ H

N > " @ @ N

Medication Adherence and


54/197

,ypoglycemic *vents After Switching toan nsulin Pen 8cont9

Pen use resulted in H@R fewer hypoglycemic events re


55/197

#ata are mean0

2A# oral antidia$etic drug0

1onconcurrent' comparative' retrospective analysis of Medicaid-enrolled patients with T"#M0 Total healthcare costs' e5cluding prescription costs' were b?L'N for patients switching to pens and b?'NH for thoseswitching to syringes0

Pawaskar M# et al0 Clin Ther. "@@NI"J/?"JL-?@0

(educed,ealth Care Costs vs Syringes

PV@0@

P;.;6

PV@0@?H'@@@

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@ T o

t a l C o s t s ' S e

c o n d 3 e a r ' b

Switching to nsulin Pens .owers


56/197

gAll-Cause Treatment Costs

(etrospective' longitudinal pre-post analysis in patients with T"#M0 Patients were followed up for at least "

years after converting from a syringe to an insulin pen0?0 .ee 4C et al0 Clin Ther 0 "@@HI"/?N?"-?N"0 "0 Co$den # et al0 Phar#acotherap$ 0 "@@NI"N/JL-JH"0

Savings b?J@>patientPV@0@?

Savings b?NL>patient

< :

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4hat Should 4e *5pect in


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pthe &uture of nsulin

+ltra - fast acting

nhaled> nasal> oral

+ltra long acting "- times per week

Com$inations of $asal insulin and G.P-?(A O %5ed > varia$le dosing


58/197

1ational Trends in Am$ulatory


59/197

'&rn!r !$ al. (a/!$!# ar! 2014;37:985D992

y Treatment of Type " #ia$etes withnsulins' ?JJN-"@?"

3ear

T r e a t m e n t E i s i t s 0 R

"@R

?R

?@R

R

@R

? J J N

? J J

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Short-Acting nsulinsntermediate nsulins

(egular nsulins.ong-Acting nsulins

S


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Summary

Type " dia$etes is a progressive disease'marked $y declining Y-cell function overtime

Additional insulin often is re


61/197

Summary

4hen● 4henever needed to achieve A?C control● Avoid futile strategies● Are there $ene%ts from early use O 2(G1

4hy● ndividuali!e therapy● Get patients to goal● Prevent complications

4hich● All insulins are e6cacious● Consider side eBect pro%les● +ltimately' choice depends on patient and

provider preferences• %hat is val"ed&



62/197

Clinical Case Study

Management of *arly Type "

#ia$etes after nitial Monotherapy&ails


VIVIAN A. FONSECA, MD, FRCP- Program ChairProfessor of Medicine and Pharmacology ) Tullis Tulane AlumniChair in #ia$etes ) Chief' Section of *ndocrinology ) Tulane+niversity ,ealth Sciences Center ) Past President' Science andMedicine ) American #ia$etes Association

.ong-standing Type " #M


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L-year-old male accountant

#ia$etes diagnosed ? year ago

Currently on lifestyle intervention and "g>dmetforminI

A?C has increased from H0R to N0R in past Hmonths

&PG has increased from ??@ - ?H@ mg>d. over Hmonths

'evie( o) *! (ith CDE reveals no signi+cant

changes in life style or $ody weight0

(elevant Medical ,istory

.ong standing Type " #MCase Study



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2$ese with weight "?L l$s for a height = ?@8;M @0N9

;P ?L>J" mm>,g &undi show a few microaneurysms

CE e5am unremarka$le

A$domen prominent with increased adipose

tissue 4aist circumference ?@" cm

Pedal pulses palpa$le

Ei$ratory and #T(s normal

Physical *5am (emarka$le &or

o g s a d g ypeCase Study



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&;G ?H" mg>dl A?C N0R

S0Creatinine ?0? mg>d.I eG&( ? m.>min>?0N m"

+>A with no Proteinuria

Al$>Creat (atio ? mcg>mg 8 1/ @-"@9 .ipid pro%le

● T0 cholesterol "?@ mg>dl● .#.-cholesterol ?? mg>dl● ,#.-cholesterol mg>dl● Triglycerides ?" mg>dl● 1on ,#. cholesterol ?HN mg>dl

.&Ts normal

T&Ts normal

(elevant .a$s

g g ypCase Study

[uestion ?


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[uestion ?

?9 ,e would $ene%t from weight reduction

"9 ,e is at high risk for a cardiovascular event9 ,is PPG e5cursions are most likely modestly

elevated

L9 ,is .#. and TGs are not at goal for T"#M9 ,is $lood pressure target should $e the same as

a patient without dia$etes

n this patient' all of the following are true e5cept/

Please *nter 3our (esponse 2n 3our Keypad

Correlation of A?C with


67/197

Average Glucose 8AG9

A?C 8R9Mean plasma glucose

mg>d. mmol>.

H ?"H N0@

N ?L 0H

? ?@0"J "?" ??0

?@ "L@ ?0L

?? "HJ ?L0J?" "J ?H0

A#A0 E0 #ia$etes Care0 Diabetes Care "@?IH8suppl ?9/S?JI Ta$le 0

These estimates are $ased on A#AG data of "'N@@ glucose measurements over months per A?Cmeasurement in @N adults with type ?' type "' and no dia$etes0 The correlation $etween A?C andaverage glucose was @0J"0 A calculator for converting A?C results into estimated average glucose 8eAG9'in either mg>d. or mmol>.' is availa$le at http/>>professional0dia$etes0org>eAG0

Current Goals of Treatment in


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Glucose control' including &PG' PPG' andA?c

Screen for status of complications

Compensate for diminished β-cell function

(e-adust pharmacotherapy and M1T

*liminate symptoms

;lood pressure and lipid control

Current Goals of Treatment in T"#

[uestion "


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[uestion "

?9 Glimepiride L mg daily

"9 Pre-dinner low dose regular insulin

9 G.P-? (A as $id'


70/197

Antihyperglycemic Therapy in Type 2 Diabetes: General Recommendations


71/197

ADA/EASD Position Statement Diabetes Care Online April !" 2#2

&ollow +p Treatment of T"# in


72/197

.iraglutide is started and titrated to ?0 mgdaily

nitial nausea had a$ated within " weeks

&PG decreased to V ?"@ mg>dl after weeks

At months A?C was H0 R and patienthad lost 0 l$

&ollow +p Treatment of T"# inPC

&ollow +p Treatment of T"# in


73/197

Glargine insulin ?@ units at ?@ PM wasinitiated and titrated to an &PG ??@ mg>dl

After weeks' the &PG was ??L mg>dl on ""

units glargine insulin> day At the month visit post lunch plasma

glucoses were ?" mg>dl' post dinner valueswere ?@ mg>dl0

At the H month visit ' A?c was N0@R' onlyone mild hypo had occurred and the weighthad increased ? kg0

&ollow +p Treatment of T"# inPC

Moving &orward


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Patients need to $e seen andevaluated at month intervals$ecause/

?9Glycemic control tends to decline withtime and therapy may need to $emodi%ed

"9*arly signs of complications must $emonitored

Moving &orward



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nsulin Therapy in Type " #ia$etes

4hen and ,ow #o 4e Start 4hen #o 4e Add,ow #o The Guidelines Guide +s

Charles &0 Shaefer' ]r0' M#' &ACPSenior Partner

+niversity Medical Group O Primary Care+niversity ,ealth Systems

Assistant Clinical Professor of MedicineMedical College of Georgia at Georgia (egents +niversity

Augusta' Georgia




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Diabetes Care 2012;35:1364–1379

Diabetologia 2012;55:1577–1596


NR


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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)


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Diabetes Care 2012;35:1364–1379 Diabetologia 2012;55:1577–1596


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,ow to Start nsulin Therapy when2 l A tidi $ ti # & il i


80/197

.ifestyle changes plus metformin

2ral Antidia$etic #rugs &ail inPatients with T"#

Com$ination of " or 2A#s

;asal nsulin Therapy

Currently Availa$le ;asal


81/197

nsulins

.ucidi #' et al0 Diabetes Care. "@??IL/??"-??L01iswender K' et al0 Clin Diabetes0 "@@JI"N/H@-H0

-Earia$ility in 1P, nsulin vs ;asal


82/197

ynsulin Analogues

.ong-acting insulin analogues are

preferred over 1P, insulin $ecausethey/ #o not e5hi$it a pronounced peak in

activity

,ave more predicta$le time-actionpro%les and less within>$etween patientvaria$ility

Are associated with less nocturnal

hypoglycemia

psed Time 8hours9d$ard , et al0 *ndocr Pract0 "@@JI?/L?-J

nsulin Glargine vs 1P, nsulin


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Added to 2ral Therapy/ &PG and ,$A?c

(iddle M' et al0 #ia$etes Care "@@I"H/@@H0

@ L ?"

?H

"@

"L

H

N

J

, $ A ? c

8 R

9

nsulin glargine1P,

NH patients previously treated with ?" 2,As and,$A?c WN0R

Mean daily insulin dosensulin glargine/ LN units 1P,/ L" units

Time 8weeks9

?@

N

@ L ?

"?H

"@

"L

& P G 8 m m o l > l 9

Time 8weeks9

H

J


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;asal nsulin Added to 2A#s Gl i C t l


85/197

mproves Glycemic Control"L week non-inferiority trial of JN insulin-nave

T"#M patients inadeday9/ nsulin glargine/ L0 nsulin detemir/ NH0

8PV0@@?9en S' et al0 Diabetes Care0 "@?@I/??NH-??N

i n A ?

C ' f r o m $ a s e l

i n e ' R

nitiating ;asal nsulin Therapy


86/197

d.

A?C X NR after " to months

Monitor &PG to determine dosage adustments

Continue regimenIcheck A?C every months

ntensify therapy

Start with ?@ + or @0? to @0" +>kg once dailya

I Administer in AM if nocturnal hypoglycemia is

a signi%cant concernI ;etter "L-hour coverage has $een o$servedwith @0L +>kg once daily

I f cost is an issue' use 1P, 8@0? +>kg twicedaily9

ES

NO


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ndications That t May ;e Timeto Stop Titrating ;asal nsulin


88/197

to Stop Titrating ;asal nsulin

;ased on individuali!ed glucosetarget 8eg' fasting AM glucose V ?@@mg>d. or fasting glucose ?@@-?@mg>d.9

4hen total insulin dose e5ceeds @0units>kg>day

.arge glucose drops overnight or$etween meals 8possi$le over-$asali!ation9

1octurnal hypoglycemia=n&h S, !$ al. Diabetes Care. 2012;35:1364D1379.

4hen s t Time to nitiatePrandial nsulin Therapy in T"#M


89/197

Prandial nsulin Therapy in T"#M

The individual is not meeting glycemictargets on $asal insulin● A?C still not at goal with @0 +>kg>day of

daily $asal insulin

● *levated A?C despite normal &PG 8in thea$sence of availa$le PPG readings9 with$asal insulin

● &PG with $asal insulin is within targetedrange' $ut PPG is persistently a$ove goal

● &urther increases in $asal insulin result inhypoglycemia

Em!ran (a/!$!# E##oa$on. Pra!ti!al Insulin+ Handb* 'r Pres!ribing Pr"iders. 3rd !d. 2011:1D68; SF%l!r S. =n: !/o?$ H, !d.

#$era,- 'r Diabetes Mellitus and Related Disrders.

El!Jandra, E: Em!ran (a/!$!# E##oa$on, =n.; 2004:207D223.

=n&h S, !$ al. Diabetes Care. 2012;35:1364D1379.

Holman RR, !$ al. N Engl J Med . 2007;357:1716D1730.

(a?d#on )B, !$ al. End!r Pra!t . 2011;17:395D403.


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4hich Agent Should 4e

Choosef ;asal nsulin &ails

Postprandial ,yperglycemiaPersists


91/197

>o"rl" ?@ "t al. Dia!"t"s R"s Clin Pract 2++82&

?HL patients with $aseline A?c ≥N0R on diet' oral agents' or insulinMealtime hyperglycemia persists after months of intensive treatme

Glucosemg>d.

22

2

1

1)

14

12

1

) 1 12 14 1) 1 2 22 24

,ours

A1C B+: #n44%

A1C ≤+: #n12%

PersistsAfter ;asal Therapy

R!la$?! on$r/&$on o* a#$n" and o#$+randal

H%+!r"l%!ma $o H/E1B D =


92/197

H%+!r"l%!ma $o H/E1B =

2n 2A#s' postprandial hyperglycemia8PP,G9 $ecomes dominant as ,$A?C

approaches goal

Monnier . et al0 #ia$etes Care0 "@@I"H/?-0&PG 8;,G9 fasting plasma glucose 8$asal hyperglycemia9

T o t a

l

H y p e r g

l y c e m i a

( % )

HbA1C

R!la$?! on$r/&$on o* a#$n" and

o#$+randal H%+!r"l%!ma $o H/E1 D ==


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o#$+randal H%+!r"l%!ma $o H/E1 ==

After treatment intensi%cation with $asal

insulin' postprandial hyperglycemia 8PP,G9contri$utes W@R of overall hyperglycemic$urden despite ,$A?c category

(iddle M' et al0 #ia$etes Care0 "@??IL/"@-"?L0&PG 8;,G9 fasting plasma glucose 8$asal hyperglycemia9

T o t a

l

H y p e r g

l y c e m i

a ( % )

HbA1C

4hen ;asal nsulin is 1ot *nough4hat Strategy


94/197

4hat Strategy

n clinical practice● Premi5 insulins

●

;asal plus 8stepwise $asal-$olus9● ;asal-$olus

● nsulin in com$ination with other

therapies 8G.P-? (A=s' #PP-L =s' SG.T"-=s'etc09

Premi5ed nsulin Added to Any Com$ination of 2A#smproves Glycemic Control in nsulin-1ave Patients


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mproves Glycemic Control in nsulin 1ave Patientswith T"#M #+(A;.* Study

I 2A#s kept at $aseline dose8s9 throughout the studyI A?C goals were maintained a median of ?H0 months with

lispro N>" and ?L0L months with glargine 8P@0L9

];' et al0 #ia$etes Care0 "@@JI"/?@@N-?@? ];' et al0 #ia$etes Care0 "@??IL/"LJ-

A C 8 R 9

,ypoglycemia#ocumented ,ypoglycemic *pisodes 8VH


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#ocumented ,ypoglycemic *pisodes 8VHmg>d.9

* p

i s o d e s p e r P a t i e n t 3 e a r PV@0@

(askin P0 #ia$etes Care "@@I"/"H@-"H0

nsulin Glargine vs N@>@ Premi5ednsulin in 2,A &ailures


97/197

nsulin in 2,A &ailures

P$#%###!

, $ A ? c

8 R

9

, y p o g l y c e

m i a D 8 e v e n t

s > p a t i e n t y e

a r 9

DCon%rmed symptomatichypoglycemia 8$lood glucose VH@

mg>d. V0 mmol>lj ]anka ,' et al0 #ia$etes Care

1N? insulin-nave

patients0nsulin glargine ` 2A#s vstwice-daily human 1P,insulin 8N@>@9&ollow-up/ "L weeks

Pharmacokinetics of Availa$le Prandialnsulins/


98/197

nsulins/(apid-Acting Analogues vs (egular ,uman

nsulin

S (E. (r&"#K(E. h$$+:GGwww.a!##da$a.*da."o?GSr+$#Gd!rG(r&"#a$(E. Em!ran (a/!$!# E##oa$on. Pra!ti!al Insulin+ Handb* 'r Pres!ribing Pr"iders. 3rd !d. 2011:1D68.

nsulin Glulisinensulin Aspart

9

9

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9

" n s # l i n ! o n c e n t r a t i

o n , m + = .

89

9

&ime, min

9 189 19 839 99 9

nsulin .ispro

" n s # l i n ! o n c e n t r a t i o n , m + = .

39

9

I9

9

@9

39

9

&ime, min

9

89

19

9 3899 189 19 839 99 9

4apid'acting analog#e 4eg#lar h#man ins#lin

9

9 189 19 839 99 9

139

189

199

9

39

" n s # l i n ! o n c e n t r a t i o

n , T " + = m .

89

9

&ime, min

9

(apid-acting analogues have more rapidonset and shorter time to peak than regular

human insulin

Timing of Prandial nsulin nections

http://www.accessdata.fda.gov/Scripts/cder/DrugsatFDAhttp://www.accessdata.fda.gov/Scripts/cder/DrugsatFDAhttp://www.accessdata.fda.gov/Scripts/cder/DrugsatFDA


99/197

nsulin .ispro? nsulin Glulisine"

?0 (assam AG' et al0 Diabetes Care0 ?JJJI""/?-?HI "0 Co$ry *' et al0 Diabetes Technol Ther 0 "@?@I?"/?N-?NNI0 .uif 3M' et al0 Diabetes Care0 "@?@I/"?"-"?I L0 American #ia$etes Association0 Practical ,ns"lin- A *andboo )orPrescribing Providers0 rd ed0 "@??/?-HI 0 Skyler ]S0 n/ .e$ovit! ,*' ed0 Therap$ )or Diabetes Mellit"s and 'elated

Disorders0

nsulin Aspart

K @ @

- K @ @ K @H @

" L @ J @ " N @

? " @ ? @ ? @ " ? @

K @ @

- K @ @ K @H @

" L @ J @ " N @

? " @ ? @ ? @ " ? @

0H kcal>kg$reakfast

Minutes

M e a n ; l o o

d G l u c o s e '

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"

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nection-Meal

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- K @ @ K @H @

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? " @ ? @ ? @ " ? @ - H @

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O@ mO? m @ m`? m

O"@ m @ m`"@ m

O@ mO? m @ m

I necting ? to "@ minutes $efore meal may reduce PPG more thaninecting at mealtime

I ;y contrast' regular human insulin needs to $e inected @ to Lminutes $efore mealsL'

;iphasic Aspart vs ;asal-Plus vs ;asaland Stepwise Prandial nsulin in T"#M/


100/197

pStudy #esign

Ro#!n#$oF . Diabetes. 2011;60#&++l 1:E20 @a/#$r 73D; $$3'

G!#c$mic 9arg$"?Fa'"i&g a&0 (r$(ra&0ia!BG


101/197

p2ver H@ 4eeks

Ro#!n#$oF . Diabetes. 2011;60#&++l 1:E20 @a/#$r 73D


102/197

and Stepwise Prandial nsulin in T"#M2ver H@ 4eeks

a P C .05 ?# B=ES. Ro#!n#$oF . Diabetes. 2011;60#&++l 1:E20 @a/#$r 73Dd. `Symptoms9

a

a

a

a

a

BIASP 4& /


103/197

y g

A?C Change &rom ;aseline tok


104/197

4eek "L

m&TT $ modi'ied intent to treat%

Da(idson )* et al% Endocr Pract 2#

+ollo,ing -.,ee r0n.in ,ith ins0lin glargine)ean AC decreased 'rom 1#%# to 34%#244 patients achie(ed AC ≤5%#+inal dose ,as #%66 7/g regardless o' reaching target

;asal ;olus nsulinPercent of Patients with ,$A?c V NR


105/197

?" trials' with"??L patients

,$A?c V NR wasachieved in

0JR 8JR C'L0OHL9 ,ypoglycemic

events

8mean>patient>@days9/ @0 8@0-?09

4eight gain

"0N k ?0-0N>&"lano !$ al. (a/!$!# R!#!arh L lnal ra$! 92 2011 1–10

*scalation from $asal to $asal-$olus increasessuccess rate in an additional ?"R to ?LR ofpatients - ,$A?c V NR is achieve in LR of patients



106/197

nsulin-;ased TherapyCase Studies

Char!$' F Sha$*$r, Jr, MD, FACP+niversity Physicians O Primary CareAssistant Clinical Professor of Medicine

Medical College of GeorgiaGeorgia (egents +niversity

Augusta' GA

Case ?


107/197

-year-old male constructionsupervisor presents with a random "hour post-prandial sugar of "@mg>dl0 ,e is asymptomatic and is in

the o6ce for a new o$ physical0 At he had acute pancreatitis0 ,isfather is overweight and has T"#0

,eight =?@ 4eight ?JH l$;M "0?

;P ?H>L

Case ?


108/197

4hat would you do ne5t

?9 (efer to comprehensive dia$etes

education"9 Treat lipid and ;P a$normalities

9 Send $lood for A?C to certi%ed la$

L9 (echeck glucose and P2C A?C


A#A Standards of Care


109/197

#iagnosis of dia$etesCo&0i"io& Cri"$ria

mpaired fastingglucose&G

&asting and glucose ?@@-?" mg>dl

mpaired glucose ToleranceGT

" h post-prandial and glucose ?L@-?JJ mg>dl

Predia$etes &G or GT or A?C 0-H0LR

#ia$etes " or more of the following/&;S X ?"H mg>dl" h post-prandial glucose X"@@ mg>dlA?C X H0R 8done in a la$using reference standard9

A#A' Standards of medical care in dia$etes -"@?"0 #ia$etes Care' "@?"I 8suppl

Case ?


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,is referenced A?C is N0HR0 ,is randomglucose on CMP was "" mg>dl0 4hatwould you do ne5t

?9 nitiate metformin and an SG.T" inhi$itorin com$ination' optimi!ing the doses

"9 nitiate metformin and optimi!e the dose

9 Start antihypertensive and statinL9 ? and

9 " and Please *nter 3our (esponse 2n 3our Keypad

(eminder on nitial #ual Therapy


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A#A suggests this option iftreatment naive with A?C W JR

AAC*/

Case ?


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After "L weeks on metformin andSG.T" inhi$itor therapy his A?C isreduced to H0LR0 ,is weightdecreases to ?J l$0 ,e has no

hypoglycemia0 ,e has return visits at L-H month

intervals with his A?C VNR $ut

gradually increasing0 At age L" his evaluation shows his

weight ?L' A?C 0?R' ;P ?">N and TC ?L' TG ?"L'

Case ?


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4hat options are availa$le to hisclinician

?9Add analog $asal insulin

"9Add G.P-? (A9Continue current treatment and

recheck in H months

L9Add a #PP-L inhi$itor9Add an S+ 8glipi!ide9


Case ?


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3ou have decided to add an analog$asal insulin

4hich $asal product will you select?91P, at $edtime

"9N@>@ premi5 ;#

9#etemir titrated to a ;# dosingL9Glargine administered once daily


Case ?


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3ou decided to add $asal insulin glargine at@0" u>kg' allowing the patient to self titrateto what endpoint

?9 &;S V ?@@ mg>dl

"9 A?C V NR

9 &;S ?@@-?@ mg>dl

L9 1o more than @0u>kg glargine


,ow to Titrate ;asal Analog nsulin


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?-?-?@@ titration?

● &rom Canadian nsight Study● Add ? unit each day until morning sugar is ?@@ mg>dl -"-? titration"

● &rom AT.A1T+S Study● Average sugars over the previous days and add " units

until morning sugar is ?@@ mg>dl -@- titrationK

● &rom Predictive @ Study● Average sugars over previous days and add units

until morning sugar is ?@@ mg>dl "-L-H- titrationL

● &airly comple5● +sed in initial Treat to Target Study

% Gerstein 8C" et al% Diabetes )ed 2##9 2;:5;9.-22% Da(ies )" et al% Diabetes Care% 2##6 24:242.4;% )eneghini


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Case ?


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,e titrates up to units of glarginedaily plus metformin and an SG.T"inhi$itor0

,is weight increases to ?J" l$0

,is A?C H0NR ,e is having nohypoglycemia0

,e continues follow up every L-Hmonths' continuing lifestyle changeand self-monitoring0

Case "


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Mary is a -year-old teacher and presentswith a ?" year history of T"#0 She has $eentreated with metformin 8"@@@ mg daily9initially and later with a G.P-? (A $ut she

could not tolerate the addition of thistreatment due to nausea0 She faithfullyfollows her lifestyle modi%cations0

An S+ 8glipi!ide9 was added and her A?C wasH0N-N0?R for several years0 She hadoccasional weak feelings0

4hen her A?C increased to N0JR her clinician

added glargine and has $een titrating for the

Case "


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,ow should you now proceed

?9 Continue to titrate $asal insulin toachieve an &;S of V ?@@ mg>dl

"9 Continue to titrate $asal insulin to anA?C U NR

9 Shift to $iphasic insulin ;#

L9 Shift from titration of $asal insulin toaddition of mealtime therapy


Assessing 4hen to Add Prandial Therapy After2ptimi!ing ;asal nsulin/ Pooled Analysis of


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nsulin Glargine Studies

Glargine was titrated $y patients according to aspeci%ed algorithm and supervised $y aclinician

&;S target was ?@@-?@ mg>dl

A?C target was U NR After "L weeks of conscientious titration of

glargine in patients with A?C W NR /● PPG was W @R of the overall glycemic

contri$ution● More hypoglycemia and weight gain seen in

those with &;S W ?@ mg>dl who continuedglargine titrationShae'er C" Reid T" DiGenio A" =la>nic A" ?ho0 R" Riddle )" Poster Presentation" ADA

Scienti'ic Sessions @0ne 2#;%

Case "


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3ou elected to use rapid actingmealtime insulin0 4hat therapy willmost easily control the A?C in thispatient with T"#

?9 Add mealtime insulin and continue totitrate $asal analog insulin to achieve a&;S V ?@ mg>dl

"9 Add mealtime insulin inections to the$asal

9 Add " mealtime insulin inections to thePlease *nter 3our (esponse 2n 3our Keypad

A?C Change &rom ;aseline to4eek "L


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4eek "L

m&TT $ modi'ied intent to treat%

Da(idson )* et al% Endocr Pract 2#

&ollowing ?L-week run-in with insulin glargineMean A?C decreased from W?@0@R to 0@R" patients achieved A?C ≤N0@R&inal dose was @0 +>kg regardless of reaching target

Case "


124/197

(apid acting analog insulin glulisineis added to the $asal insulin 8L"u


125/197

nsulin

nitiate● ?@R $asal insulin dose as rapid acting analog insulin at

largest meal of the day

2(● L units rapid acting analog insulin● And titrate upward

Titrate● `" units every days until glucose is in range 8 U ?@ mg>dl9● @ concept

ADA" Diabetes Care 2#: ;- s0ppl B: S.S9


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127/197

#evices and #elivery Systems fornsulin

Ja& Pa%!o Fria', MDPresident' 1ational (esearch nstitute' .os Angeles' CA

Assistant Clinical Professor of Medicine+niversity of California' San #iego

Technological Advances in nsulinAdministration

and Glucose Monitoring

#ia$etes #evice *volution


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nsulin #elivery #evicesEial>Syringe' Pen and Pump


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Via! a&0S#ri&g$ I&'!i&P$&

I&'!i&Pm(


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.ive demonstration ofvial>syringe and pen

Advantages and #isadvantages nsulin Pen 8vs0


131/197

&ddh% R, !$ al. J #$er . 2011 &l% 15 @EA

)a"wr! ). J #$er . 2011;18:392D402

S!lam D. J Diabetes &!i #e!$nl . 2010;4:505D13

Eial>Syringe9

A0a&"ag$' Greater accuracy

.ower rates ofhypoglycemia after

switch (eduction in comple5ity

8ease-of-use9

mproved convenience

.ess fear of inection

Greater treatmentsatisfaction

mproved Syringe


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*&$n!r E, !$ al. Current Medi!al Resear!$ and O,inin 2013;295, 475D481

PV@0@

M e a n a $ s o l u t e $ i a s 8 + 9

M e a n

a $ s o l u t e $ i a s

8 + 9

Patients ,CPs>Caregivers

Similar #osing Accuracy ofCurrently Availa$le nsulin Pens


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Mr%won, !$ al. Diabetes #e!$nl #$err 2012;142:804D9.

+ dose H@ + dose

S( &P 1G&P KP

0? 0LN 0L"

L0L L0LL L0LNL0N

+ n i t

+ n i t

H

L

H

H@

N

0 H@0" H@0?@H@0L H?0@L

0L 0J

N0N

0@

S( &P 1G&P KP

SR" SoloSTAR

+P" +lePen

FG+P" Fet Generation +lePen

P" ,iPenH

Patient and ,CP Preference'*6cacy and Safety of Pen vs0


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Eial>Syringe

Ehmann E, !$ al. Diabetes #e!$l #$er 2014;162, 76D83

Patients Preferrednsulin Pen 2ver


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Eial>Syringe

Ehmann E, !$ al. Diabetes #e!$l #$er 2014;162, 76D83

!"erall$reere&ce

'l(co)eCo&trol

!"ercome *&)(li&+e)i)ta&ce

Lo&g,term -)e


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137/197

*conomics of nsulin Pen +se,igher Prescription $ut .ower 2verallC t


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Total mean all-cause annual treatment costswere reduced $y b?'J@ per patient 8P V@0@?9

Annual hypoglycemia-attri$uta$le costs werereduced $y bN per patient 8P V @0@?9

Annual dia$etes-attri$uta$le costs were

reduced $y bH@@ per patient 8P V @0@?9

!! W, !$ al. Clin #$er 2006;28:1712D25.

Cost

Practical ssues 4ith Pen +se


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Training aids

Storage conditions and handling

4here on the $ody to inect

Pen needle disposal

#o not share pen 8even with new needle9

(eim$ursement andPatient Assistance

P


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Third party coverage of insulin pens

Patient Assistance Programs

D 1ovo 1ordisk

D Sano%

D .illy

Programs

nsulin Pump Therapy in PatientswithT pe " #ia$etes F&ailing M#


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Type " #ia$etes F&ailing M#

Therapy

?H-week' uncontrolled' multicenter study

"? patients not reaching A?C targets with M#therapy 8Q2A#9

Age N yrI Total daily insulin ?@@ +I A?C 0LR

nitiated insulin pump therapy 8Animas "@"@9

F;est possi$le control with the simplest possi$ledosing regimen

ra# , !$ al. J Diabetes &!i #e!$nl 2011;54:887D893 NP J991, NNP J9991 compared to aseline

E-Go/ #isposa$le nsulin #elivery#evice


142/197

Prede%ned $asal dose-"@' @ and L@ +nits>"L hrs

;olus delivery-" units per push

-Ma5imum H units>"L hrs

Ma5 capacity NH +>day

?-day use 8fully disposa$le9

1o electronics' no $atteries' notu$ing

1o programming re


143/197

ContinuousE(i'o0ic G!co'$Mo&i"ori&g

Co&"i&o' G!co'$Mo&i"ori&g


144/197

Convergence of TechnologiesPathway to Arti%cial Pancreas


145/197

Summary


146/197

Signi%cant advances in insulin delivery and

glucose monitoring devices have $een made overthe past " decades

nsulin pens oBer a safe' e6cacious and cost-eBective method of insulin delivery

1umerous studies have shown improved patientsatisfaction and preference with insulin penscompared to vial>syringe

FPatch insulin pumps tailored speci%cally topatents with type " dia$etes are availa$le andeBective

Glucose monitoring is an important component of

dia$etes therapy particularly in insulin-treated



147/197

nteractive Case Study

*Bective +se of nsulin Pens in Type " #ia$etes

Ja& Pa%!o Fria', MDPresident' 1ational (esearch nstitute' .os Angeles' CAAssistant Clinical Professor of Medicine+niversity of California' San #iego

Case Study/ Susana


148/197

H-year-old .atino female

Type " dia$etes diagnosed ?" years ago

PM,/ ,T1' dyslipidemia' o$esity and

osteoarthritis

Social history/ 4aitress at $reakfastrestaurant' no health insurance

Case Study/ Susana


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Medications/- Metformin ?@@@ mg ;#- Glimeperide Lmg [#

- N@>@ insulin @+ ;# 8pre-$reakfast and pre-dinner'vial>syringe9

- ,CT: " mg [#' lisinopril "@ mg [#' atorvastatin ?@ mg[#

States that she fre


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,eight =LI weight "@ l$s 8;M kg>m"9

;P?"L>"

A?CJ0?R 8goal VN0@RI H months ago

J0"R9 &asting glucose in ?H@-?J@ mg>d. range

past " weeksI no hypoglycemia

Total cholesterol?JL mg>d.I .#.-C?"@mg>d.' ,#.-CL" mg>d.' TG?H" mg>d.8non-,#.-C?"9

1ormal renal and liver function


151/197

[uestion "


152/197

1 #iscuss medication adherence

8 #iscuss nutrition and physical activity

3 Consider aspirin therapy

@ Consider increasing atorvastatin dose

All of the a$ove

4hat else would you consider during Susana=s

visit



153/197


154/197

Case Study/ Susana


155/197

(eturns to your o6ce in "0 months

nsulin glargine L + [,S

1o further issues with skipping insulin

doses1o hypoglycemia

A?C N0RI N-day average fastingglucose ?@ mg>dl

Gained H l$s

[uestion


156/197


157/197

nitiated liraglutide at @0H mg [# andincreased to ?0 mg [# over su$se


158/197

A?C

@0JR 8to H0JR9 and $ody weight

l$s over the ne5t -L months

A?C sta$le over a J month period on

metformin ?@@@ mg ;#' liraglutide ?0mg [# and insulin glargine L@ + [,S



159/197

Advances in the#evelopment of 1ew

.ong-acting nsulin&ormulations

.uigi Meneghini' M#' M;A

Professor' #epartment of nternal Medicine

+T Southwestern Medical Center

ACP Symposium#uality of nterest #eclaration


160/197

, report the )ollo(ing potentiald"alit$/d"alities o) interest in the +eldcovered b$ #$ lect"re-

*onorari"# 0 Novo Nordis sano+2aventis 3oehringer2,ngelhei#*alo4$#e'esearch 0 sano+2aventis3oehringer2,ngelhei# MannindP+4er

Luigi Meneg!ini


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mportance and limitations of

insulin therapy Goals evolution of current

$asal analogs

.onger acting $asal analogs● Pharmaco -kinetics -dynamics● *6cacy● ,ypoglycemia● 2ther considerations

• E!ercise stacing 5 6e!ibilit$


162/197

mportance of nsulin

Therapy and GlycemicControl

#ecrease in historical risk ofmicrovascular complications


163/197

microvascular complications

CCT>*#C Study Group0 ]AMA "@@I "J@/ "?J-"?HN


164/197

.imitations of nsulin

Therapy

)edications most commonly associated,ith emergency hospitalisation


165/197

Iar'arin

#

6"###

#"###

6"###

2#"###

26"###

;#"###

;6"###

#

6

#

6

2#

26

;#

;6

Estimated n0mber o' hospitalisations Percentage o' estimated n0mber o' hospitalisations

Data gi(en are n0mber and percentage o' ann0al national estimates o' hospitalisations% Data 'rom the FE&SS.CADES pro>ect%ER (isits n$296"4#2/Total cases n$2"999% ER" emergency room OAD" oral antidiabetic dr0gs*0dnitJ et al % N Engl J Med 2#;96:2##2K2

5% o all e&/ocri&e emerge&cy o)pitali)atio&)i& people 65 year) are ca()e/ by ypoglycaemia

S!?!r! H%+o"l%!ma Ba#!d on

() '%+!, 'r!a$m!n$ L (&ra$on


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() '%+!, 'r!a$m!n$ L (&ra$on

Em!l. (a/!$ )!dn! 2008; 25: 245D254 G M H%+o"l%!ma S$&d% >ro&+. (a/!$olo"a 2007;50: 1140

Di0rna istri 0tion ohypoglycemia in ,ell.

t ll d ld l ith T2D)


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controlled elderly ,ith T2D)

,ay .C et al0 #ia$ Tech Ther "@@I 8?9/ ?J-"H


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E(ol0tion o' c0rrent basal

analogs

Desirable characteristics o'in>ectable basal ins0lin


169/197

in>ectable basal ins0lin

I Etended d0ration o' action – 2- hrs or longer

I +lat pharmacodynamic pro'ile – minimal to no pea e''ect

I Red0ced day.to.day (ariability – Predictable blood gl0cose response

ZD a0mi&i'"ra"io&

Lo ri'3 o* &oc"r&h#(og!#c$mia


170/197


171/197


172/197


173/197

Serum concentration and half-life of insulin degludec and


174/197

insulin glargine

egl(/ec 'largi&e

0.4 -g 0.6 -g 0.8 -g 0.4 -g 0.6 -g 0.8 -g

Hal,lie

ho0rsB26%! 25%# 2;%! %4 -%# %!

ea& al,lie 25.4 12.5

Deg #%4 7/gGlar #%4 7/g

8eise et al. Diabetes 2#9#S0ppl% B:


175/197

?0 ,umalog' +S prescri$ing information' "@??0"0 ,ansen (]' et al0 A#A "@?" a$stract JH-P0 Sinha et al0 A#A "@?" a$stract ?@H-PL0 Meloun ;' et al0 7E3 Lett. ?JNI/?L-?N0

.Q89@@31

U8 0a

2olyethylene

-lycol !hain8

U89 0a

I&'!i&Li'(ro<

6. 3Da

#nctional si5e8,

I17 0a

Larg$ h#0ro0#&amic 'i$ 0$!a#' i&'!i& a%'or("io&

a&0 r$0c$' c!$ara&c$ r$'!"i&g i& (ro!o&g$0

Pegylated


176/197

! #D# :;


177/197


178/197


179/197

years

,4 et al #ia$et Med "@? Aug ?J doi/ ?@ ????>dme ?"@ *pu$ ahead of printj

A?C

&PG

SM;G

D$g!0$c'G!argi&$

. spro: m arred0ction in Type 2 diabeteson prior basal


180/197

on prior basal

nstal (M et al #ia$etes Care "@?"I / "?L@O"?LN

1S

1S

PEG-Li'(ro'G!argi&$

Similar glycemic control bet,eenGlargine 7;## (s% 7## in T2D)on basal OADs


181/197

ed at the "@? nternational #ia$etes &ederation meetings in Mel$ourne Australia


182/197


183/197

,4 et al #ia$et Med "@? Aug ?J doi/ ?@ ????>dme ?"@ *pu$ ahead of printj

2verall hypoglycemia

1octurnal hypoglycemia

D$g!0$c'G!argi&$

1octurnal ,ypoglycemia in Phase Treat-to-Target (CTs/ #egludec vs0Glargine


184/197

Glargine

• aP V 0@0

• ;' $asalI ;;T' $asal-$olus therapyI ;`2A#s' $asalplus 2A#sI &.*' e5i$le $asal degludec dosing' -

• (ussell-]ones #.' et al0 Diabetes0 H?8suppl?9/ AH@ a$str "J-P2j0

aaaa

8ypoglycemia &ncidence d0ring 2Iees o' Treatment in Type 2Diabetes on Prior *asal


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abetes o o asaP@0?H

P@0?

enstal (M et al #ia$etes Care "@?"I / "?L@O"?LN

2verallhypoglycemia

1octurnalhypoglycemia

PEG-Li'(ro

'G!argi&$


186/197

ed at the "@? nternational #ia$etes &ederation meetings in Mel$ourne Australia

D Severe hypoglycemia 8all9occurred in ?0@R and ?0R of

+@@ vs +?@@ su$ects


187/197

Eercise and hypoglycemia

+re0ency o' eercise.relatedcon'irmed hypoglycaemic e(ents


188/197

O(erall con'irmedhypoglycaemia

Foct0rnal con'irmedhypoglycaemia

**" basal bol0s *OT" basal.oral therapy

8eller et al Diabetes 2#;92S0ppl B:A45

$atie&t,reporte/ re)(lt)&Deg OD&Glar OD


189/197

S0pplementing C8O more e''ecti(e thanred0cing daily ins0lin dose to pre(enteercise.ind0ced hypoglycemia


190/197

>rmm !$ al (a/!$!# )!$a/ 2004; 30: 465D70

Gro( A8n?9

1o 1S `?@-"@g C,2>hr

Gro( B8n?N9

1S ?@`R`?@-"@g C,2>hr

Gro( C8n?N9

1S ?@`R1o C,2

Gro( D8n?9

1o 1S 1o C,2

Meandailyinsulindosereduction

of "@-"R

Car$ohydratesupplementation


191/197


192/197

Physiologic stacing o' basal ins0lin

preparations

+irst order inetics o' basalins0lin


193/197

e T Meneghini . *ndocrine Pract 8in print for "@?L9

Steady state ins0lin concentrationachie(ed ,ithin ;.- days ,ith glargine7;##


194/197

esser A et al #ia$ 2$esity Meta$olism "@?LI *pu$ ahead of printj #2/ ?@ ????>dom ?""


195/197

Dosing regimen: +orced'leible

Mo& 9$ $0 9h Fri Sa" S&


196/197

Mo& 9$ $0 9h Fri Sa" S&

mor&i&gmor&i&g mor&i&g

e"e&i&g e"e&i&g e"e&i&g e"e&i&g40 40

8

24

8

40

Meneghini et al. Diabetes Care "@?IH/OHLI Mathieu et al. J Clin Endocrinol Metab "@?IJ/??LOH"

ID$g OD ]$

T"/ A?C T"/ nocturnal hypo

T?/ A?C T?/ nocturnal hypo

S0mmary


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I

acp insulin slidecast 222

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