premix analogue vs premix human insulin in clinical practice (1)

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 Dr Ravi Kant Premix Analogue VS. Premix Human Insulin In Clinical Practice

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8/16/2019 Premix Analogue vs Premix Human Insulin in Clinical Practice (1)

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Dr Ravi Kant

Premix Analogue VS. Premix Human Insulin InClinical Practice

8/16/2019 Premix Analogue vs Premix Human Insulin in Clinical Practice (1)

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Agenda

• Objectives• The pharmacological differences between premixed insulin

analogue and premixed human insulin BHI !• "fficac# and safet# with BI$sp ! and BHI !% evidence

from R&T and meta'anal#sis•

(witching from BHI ! to BI$sp !• &ost' effectiveness• &ase (tud#

BHI) biphasic human insulin* BI$sp) biphasic insulin aspart

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8/16/2019 Premix Analogue vs Premix Human Insulin in Clinical Practice (1)

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The dual-release insulin conce t

+h#sio

+rotaminsulin

(oluble

BI$sp

(chematic presentati

,arber et al. Diabetes Obes Metab -!!.*/%0 !1/

Ph!siologicalinsulin ro"ile#

Basal component2eal'related pea3s

Rapid'actinginsulin

analoguestogether with a

basal insulinprovide

ph#siologicalinsulin

replacement

$nalogue mixinsulins such as

BI$sp ! replaceboth

meal'related and

basal insulin

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!4

+rotamine'cr#stallisedinsulin aspart

(oluble insulin aspart

$IAs %&A remixedsus ension o"#

!4

5+H insulin

Ho' is $IAs %& di""erent "rom $HI %&(

BHI !BI$sp !

.!4 .!4

Regularhuman insulin

$HI %A remixed

sus ension o"#

5ovo 5ordis36 BI$sp ! (+&6 http%77ec6europa6eu7health7documents7communit#'register7-!!!7-!!!!8!9 . !7anx: . !:en6pdf

BI$sp) biphasic insulin aspart* BHI) biphasic human insulin* 5+H) neutral protamine Hagedorn

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Proo" o" conce t# ra id absor tion and higherea) concentration

Time

( e r u m

i n s u l i n ; m < 7 = >

-?

-!

9?

9!

?

!8%!! 99%!! 9@%!! 9.%!! -!%!! - %!! -%!! ?%!! 8%!!

AAA

$dapted from acobson et al. Eur J Clin Pharm -!!!*?0% //1@!AAA p C!6!!!9* n -@

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*aster absor tion o" $IAs %& is re"lected inthe earlier onset o" serum glucose lo'ering

Time

( e r u m g l u c o s e

; m m o l 7 = >

?6?

?6!

@6?

@6!

6?

6!

!8%!! 99%!! 9@%!! 9.%!! -!%!! - %!! !-%!! !?%!! !8%!!

$dapted from acobson et al. Eur J Clin Pharm -!!!*?0% //1@!

8/16/2019 Premix Analogue vs Premix Human Insulin in Clinical Practice (1)

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*p C!6!? in favour of BI$sp ! for lower ++, levels after dinner and brea3fast* n 9

++,) postprandial plasma glucose

T'ice-dail! $IAs %& in atients 'itht! e + diabetes# im roved PP, control

98%!!

-!

9!

?

!

9?

98%!! --%!! !8%!! 9 %!!

A A

Time

B l o o d g l u c o s e

; m m o l 7 = >

$dapted from 2c(orle# et al. Clin Ther -!!-*-@%? !1/

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Pharmacological ro"ile

&ompared with BHI) BI$sp ! has%

Easterabsorption

Higher pea3concentration

2ore rapidand

pronouncedglucose'lowering

effect

(imilarduration of

action ofbasal

component

acobson et al. Eur J Clin Pharm -!!!*?0% //1@!

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""icac! and sa"et! 'ith $IAs %&and $HI %&# evidence "rom CTs and

meta-anal!sis

R&T) randomised controlled trial6

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/ong-term com arison o" e""icac! and sa"et! o"$IAs %& vs. $HI %&

Insulin'using patients witht#pe 9 and t#pe - diabetes

;n -/@>

BI$sp ! ;n 9@!>

BHI ! ;n 9?9>

months

One screening visit*patients alread# using a

twice'dail# insulin regimen

$dapted from Boehm et al 6 Diabet Med -!!-*9/% / 1//* Boehm et al6 "ur Intern 2ed6 -!!@*9?%@/0'?!-6

BHI) biphasic human insulin* BI$sp) biphasic insulin aspart

-9 months

"xtension period

Initial period

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/ong-term com arison o" e""icac! o" $IAs %&vs. $HI %&

-@ months!

9

-

@

?

0

.

8

/ 86 ? 869

H b $ 9 c a t

- @ m o n t h s

; 4 >

BI$sp !

BHI !

BHI) biphasic human insulin* BI$sp) biphasic insulin aspart* 5() not significant

Boehm et al6 "ur Intern 2ed6 -!!@*9?%@/0'?!-6

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Im roved ost randial blood glucose 'ith $IAs %& vs. $HI %&

$fter 9- wee3s of treatment) levels of Hb$ 9c did not differbetween the two treatment groups

2ean difference% F!6!9 ;/!4 &I% F!69@*!69->

0

0

0

B l o o d g l u c o s e

; m m o l 7 = >

!+re'

9!

9-

+ost'

8

0

BI$sp !

BHI !

0

=unch+re' +ost'Brea3fast

+re' +ost'Dinner

Bedtime !-6!! h

*p C!6!?

Boehm et al 6 Diabet Med -!!-*9/% / 1//

BHI) biphasic human insulin* BI$sp) biphasic insulin aspart* &I) confidence interval

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educed major h! ogl!caemia 'ith $IAs %&vs. $HI %&

9st #ear -nd #ear!

-

@

0

8

9!

9-

events

99events

8events

+ a t i e n t s w i t h a t

l e a s t o n e m a j o r

h # p o g l # c a e m

i c e p i s o d e

; 4 >

p 5(

p !6!@

BHI) biphasic human insulin* BI$sp) biphasic insulin aspart* 5() not significant

Boehm et al6 "ur Intern 2ed6 -!!@*9?%@/0'?!-6

!events

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Similar change in HbA 1c 'ith remixed humaninsulin vs. $IAs %&• (uperior with premix insulin analogues vs6 long'acting insulin analogues or non'insulin therap#

'96- '9 '!68 '!60 '!6@ '!6- ! !6- !6@Eavours premixed

analogueEavours

comparator

Com arison

=ong'acting insulin analogue vs6%$ll premixed insulin analoguesInsulin aspart .!7 !Insulin lispro .?7-?Insulin lispro ?!7?!

$ll premixed insulin analoguesInsulin aspart .!7 !Insulin lispro .?7-? G

Insulin lispro ?!7?! G

+remixed human insulin vs6%

$ll premixed insulin analogues

Insulin aspart .!7 !

Insulin lispro .?7-?Insulin lispro ?!7?!

$ll premixed insulin analogues

Insulin aspart .!7 !

2ean di""erence o" changein HbA 1c level 3456 CI78 6

Studies3 artici ants7

'!6 / ;'!6?!*'!6-8>'!6@8 ;'!609*'!6 @>'!6 ;'!6@8*'!69.>'!6@! ;'!60?*'!69?>

99 ; 9!8>@ ;/.0>? ;9.-!>

;? !>

'!6!? ;'!69?*'!6!@>!6!0 ;'!6!@*!690>

'!6!0 ;'!6-0*!69@>'!6!0 ;'!6 ?*!6- >

/ ;-.9.>@ ;.!8>

;9@//> ;--0>

9! ;-@-->/ ;9/-9>. ;9?9!>0 ;9!!/>

;/9->5o data

'!6@/ ;'!680*'!69->'!6?? ;'!6/@*'!690>'!6?- ;'96!!*'!6!@>'!609 ;'969 *'!69!>'!6@- ;'96!!*!690>

5oninsulin antidiabetic agents vs6%

G+ooled results include those of a stud# that administered insulin lispro ?!7?! in the morning and insulin lispro .?7-? in the evening6 &I) confidence interval

$dapted from a##um et al. Ann Intern Med -!!8*9@/%?@/1?/

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$IAs %& associated 'ith a signi"icantl! lo'er rateo" nocturnal h! ogl!caemia com ared 'ith $HI %&

Iwamoto -!! ;n @-8>

-!!6-

!6?. !6-!*96?8L) p !6-8

!68/ !6-?* 690L) p !680

!6@@ !6--*!68/L) p !6!-

96! !6@-*-6? L) p !6/?

96! !6 8*-6.0L) p !6/0

96!? !699*9!6!/L) p !6/.

9? 0 ;n 9/?>

-6@ !6 9*986/!L) p !6 /

!69 9 9!

!!0 ;n 9! >

Overall

!6 !6-9*!6?9L) p C!6!9

!6@@ !699*[email protected]) p !69.

!6?! !6 8*!60.L) p C!6!9

I - -4

2c5all# et al. -!!. ;n 90!>

Kilo et al. -!! ;n / >

9 /@ ;n -/->

BioeJuivalence trial ;n 0>

Boehm et al. -!!- ;n 98.>

9- @ ;n 98!>

Davidson et al. Clin Ther -!!/* 9%90@91?9

Trial ate ratio 3456 CI7

Eavours BI$sp !

EavoursBHI !

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S'itching "rom $HI %& to $IAs %&

BHI) biphasic human insulin* BI$sp) biphasic insulin aspart

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eal-li"e s'itching "rom $HI %& to $IAs %&#HbA 1c

H b $ 9

c c h a n g e a f t e r

0 m o n t h s

; 4 > -+.+10 -+.1%0 -+.+90 -+.+:0

I2P OV +

H b $ 9

c c h a n g e a f t e r

0 m o n t h s

; 4 >-1.;000 -1.<

A p C!6!? for all comparisons vs6 baseline* AA p C!6!!9* AAA p C!6!!!96 BI$sp) biphasic insulin aspart* BHI) biphasic human insulin

96 (hesta3ova et al. Curr Med Res Opin -!!.*- % -!/19@* -6 (hah et al. Int J Clin Pract -!!/*0 %?.@18-* 6 "l 5aggar et al. Diabetes Res Clin Pract -!9-*/8%@!81

P S =T 1 Overall o ulation

A1 chieve %

-1.400

'-6!

'96?

'96!

'!6?

!6!

-1.<

'-6!

'96?

'96!

'!6?

!6!

-1.;000

H b $ 9

c c h a n g e a f t e r

0 m o n t h s

; 4 >

'-6!

'96?

'96!

'!6?

!6!

Baseline value /694

Baseline value /6-4Baseline value /6 4

-1.:00

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eal-li"e s'itching "rom $HI %& to $IAs %&#*P,

-+.+10 -+.1%0 -+.+90 -+.+:0

I2P OV +

-1.;000 -1.<

AA p C!6!!9* BI$sp) biphasic insulin aspart* BHI) biphasic human insulin

96 (hesta3ova et al. Curr Med Res Opin -!!.*- % -!/19@* -6 (hah et al. Int J Clin Pract -!!/*0 %?.@18-* 6 "l 5aggar et al. Diabetes Res Clin Pract -!9-*/8%@!81

P S =T 1 Overall o ulation

A1 chieve %

-1.400

' 6?' 6!'-6?'-6!'96?'96!'!6?!6!

-+.4+

'@6!

' 6!

'-6!

'96!!6!

-%.9;00

' 6?' 6!'-6?'-6!'96?'96!'!6?

!6!

Baseline value 9!6- ;mmol7=>

Baseline value 9!6 ;mmol7=Baseline value 996! ;mmol7=>

-%.&00

E + , c h a n g e a f t e r

0 m o n t h s

; m m o

l 7 = >

E + , c h a n g e a f t e r

0 m o n t h s

; m m o l

7 = >

E + , c h a n g e a f t e r

0 m o n t h s

; m m o l

7 = >

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eal-li"e s'itching "rom $HI %& to $IAs %&#PP,

-+.+10 -+.1%0 -+.+90 -+.+:0

I2P OV +

-1.;000 -1.<

AA p C!6!!9* BI$sp) biphasic insulin aspart* BHI) biphasic human insulin

96 (hesta3ova et al. Curr Med Res Opin -!!.*- % -!/19@* -6 (hah et al. Int J Clin Pract -!!/*0 %?.@18-* 6 "l 5aggar et al. Diabetes Res Clin Pract -!9-*/8%@!81

P S =T 1 Overall o ulation

A1 chieve %

-1.400

'?6!

'@6!

' 6!

'-6!

'96!!6!

-9.:5

'06!

'?6!

'@6!

' 6!

'-6!

'96!

!6!

-5.9;00

'?6!

'@6!

' 6!

'-6!

'96!

!6!

Baseline value 9@6- ;mmol7=>

Baseline value 9@6/ ;mmol7=Baseline value 9?6 ;mmol7=>

-9.%00

+ + , c h a n g e a f t e r

0 m o n t h s

; m m o

l 7 = >

+ + , c h a n g e a f t e r

0 m o n t h s

; m m o l

7 = >

+ + , c h a n g e a f t e r

0 m o n t h s

; m m o l

7 = >

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A1 chieve# >ualit! o" li"e "ollo'ing s'itch "rom$HI %& to $IAs %&

! -!9! ?!@! .! 8!! 0!

Morstisual analogue scale

! worst imaginable health state9!! best imaginable health state

Baseline0@6!

;(D 906 >

Mee3 [email protected]?

;(D 996/>

BI$sp) biphasic insulin aspart* BHI) biphasic human insulin* (D) standard deviation

Improvement9-6? points

"l 5aggar et al. Diabetes Res Clin Pract -!9-*/8%@!819

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Cost-e""ectiveness o" s'itching "rom$HI %& to $IAs %&

BHI) biphasic human insulin* BI$sp) biphasic insulin aspart

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S'itching "rom thera ! 'ith $HI %& or insulin glargine ?OA@s to $IAs %& ? OA@s im roves li"e ex ectanc!

Increase inlife

expectanc#;#ears>

!6.

India

96?

!6?

196?

1!6?

Indonesia (audi $rabia

!6/96-

Change in li"e ex ectanc! "ollo'ing change "romthera ! 'ith $HI %& or insulin glargine ? OA@s to

$IAs %& ? OA@s

India

(audi $rab

196

!6/

96!

!

196!

$HI %& ? OA@s to $IAs %& ? OA@s Insulin glargine ? OA@to $IAs %& ? OA

Decrease inlife

expectanc#;#ears>

G(imulated over ! #earsO$D) oral antidiabetic drug

,upta et al. J Med Econ -!9?*98%-0 1.-

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S'itching "rom $HI %& to $IAs %&# incidence o"com lications 3CO @iabetes 2odel simulation7

,upta et al. J Med Econ -!9?*98;@>%-0 −.-

R e d u c t i o n

i n i n c i d e n c e

; 4 p e o p l e >

BHI) biphasic human insulin* BI$sp) biphasic insulin aspart* &OR") The &entre of Outcomes Research

(evere vision loss "nd'stage renal disease 2#ocardial infarction <lcer

'9!6!

'?6!

!6!

'-60

'@6@

'?6.

''96/

'?69

' 68

'.6? '.68

'06-

India ;n 800> Indonesia ;n 9.?> (audi $rabia ;n @!9>

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S'itching "rom $HI %& to $IAs %& results in arojected dela! in onset o" com lications

,upta et al. J Med Econ -!9?*98;@>%-0 −.-

BHI) biphasic human insulin* BI$sp) biphasic insulin aspart*

$n#complication

2#ocardialinfarction <lcer (evere vision

loss"nd'stage

renal disease

2acrovascular complications 2icrovascular complications$ge at diagnosis

@@60

@@60

?06

?069

0?69

0@6-

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S'itching "rom $HI %& to $IAs %&# sensitivit!anal!ses sho' cost-e""ectiveness to be robust

,upta et al. J Med Econ -!9?*98;@>%-0 −.-

BHI) biphasic human insulin* BI$sp) biphasic insulin aspart* &OR") The &entre of Outcomes Research

! !6? 9 96? - -6? 6?

!6!9

!6!-

!6!

!6!9

!69.

96-

96-@

96-/

96-?

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!6-.

!6-8

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Saudi Arabia Indonesia India

Base effect

Base effect

2edian treatment effect ;Hb$9c>

5o Hb$9c deterioration

?!'#ear time horiNon

%&-!ear anal!ses

1-!ear anal!ses

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Case Stud

Case Stud!

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2r Om)ar• Age# ?-• @iagnosis# t#pe - diabetes since -!!8• Current em lo!ment# (hop3eeper• HbA 1c # .6/4• Beight# .. 3g• Height# 9609 m• $2I# -/6. 3g7m -

• @iabetes treatment# human premix insulin -? for - #ears ;/ 3g weight gain since start of insulintreatment>) metformin) sitagliptin

2edical histor!# asthma ;inhaled steroids>) s#mptomatic h#pogl#caemia nearl# ever# da# during hismorning wor3• /i"est!le# occasional alcohol inta3e* stressful job* earl# morning starts

Case Stud!

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Case Stud!

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Interactive >uestion

Case Stud!

Case Stud!

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2r Om)ar$lood glucose ro"ile +

• In the evening ;@ wee3s later> he consumes alcohol) and his wife has to call the emergenc# ambulanceduring the night due to severe h#pogl#caemia6 It is totall# unclear what insulin he had injected andwhen6

5+H) neutral protamine Hagedorn* RHI) regular human insulin

Bhat is the cause o" the severe h! ogl!caemia(

Case Stud!

• (witch

+r8'9Ba9-

• (till exminorevent

Has to

Case Stud!

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2r Om)ar$lood glucose ro"ile %

• Me change the regimen to insulin BI$sp ! 9@'!'9@ I<6 In the following wee3s the dose istitrated to 90'!'98 I<

Case Stud!

Case Stud!

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Ho' did 2r Om)ar "are(

Case Stud!

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Thanks for patient hearing