Gliptins- Evaluation

7/23/2019 Gliptins- Evaluation

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Gliptins: Current Status

& Future Promise


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Background

Treatment of diabetes has undergone majorchanges in last decade

Ne drugs ith ne mechanisms of action ha!ebeen introduced

"b#$c%target is often not reached in spite ofman' glucose%loering strategies

(an' therapies increase risk for h'pogl'cemia

#ctions be'ond blood glucose control arearranted)


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31%

69%

37%

63%

Europe

(CODE-2)1

USA

(NHANES)2 HbA1c < 7%

HbA1c > 7%

1. Liebl A et l. Dibetolo!i "#$S23 2&&2' 2. S* SH et l. +A,A 291$33# 2&&"' 3. Leiter

LA et l. C + Dibete 37$/2 2&13

HbA1c-targets often not reached

C

(D0E)3

#3%

"7%


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Heie et l. ,+ 333$12&& 2&&6

Another problem is thatwe intensify therapy late


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Early treatment

More aggressive intensication oftreatment

Durable treatment with beta-cellpreservation

This gives us the lessons for newphilosophy

Time ! do more


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Maintained "#T in 1! years

Developed $#T after year %A*r4 Dibete #/$726-731 2&&9

Time &years'

* + , - . $* $+#lucagons

ecretion

&ng(mm

ol'

%.

%-

%,

%+

// /

Time &years'

* + , - . $* $++

0

,

1

-

2

$nsulin

secretion

&nmol(m

mol'

/ / /

uli e5retio lu5!o e5retio

Dual islet defect occurs early duringdevelopment of T!D


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$sletDysfunction

$mpaired insulin secretionAugmented glucagon secretion

$nsulin)esistance

Main pathophysiological defects in T!D

#lucose utili*ation +Hepatic glucose production , 3 "'pergl'cemia


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#oal Metformin

. T/D

D00-i

#2T-!i

$nsulin

, $nsulinsensitivity

4 4 4

, $nsulin

secretion

4 4 546

+ #lucagonsecretion

7 4

Mechanisms of glucose-loweringtherapy in

relation to goal for early intervention


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3hat #liptins Add to T!DM Therapy

Comprehensive mechanism of action Targeting multiple levels in T!DM pathophysiology

Dual targeting of 4 cells and 5 cells

Improvement in Disposition/Adaptation Index

$mprovement in both $nsulin secretion 6 $nsulinsensitivity

Glucose dependent secretion of Insulin secretion

2esser ris7 of hypoglycemia

Targeting postprandial and overall glycemia

Preservation of Beta cells

timulate 5 cell neo-genesis

)educe 5 cell apoptosis

Eects !eyond !lood sugar lo"ering#$

r + Dibete 5 Di. 2&&6'6(#)$2&7-21#

re erri 8r5ti5l !uie to t*e 5re o t*e :ei5l ptiet Si;t* eitio 2&&"Apte ro: A*r4 et l. Dibete Cre. 2&' 2/$ 1936


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Gliptins# %ultiple !ene&ts

Targets pathophysiology through both beta- and alpha-cells

$mproves glycaemic control8

8educe "b#$c in patients ith t'pe + diabetes b' 9$)$)educes both 90# and 00#

High tolerability and safety

2ow ris7 of hypoglycemia

3eight-neutral

A*r4 et l. Dibete Obe ,etb 13$77#


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:ildagliptin reduces glucagonand hepatic glucose release

overnight

,el

B

B BBB

B

B

B;=

;=

;?=

;!=

;1=

=

1=

!=

1@8==

Time

Delta #lucagon &ng(2'

!=8== !?8===!8== =>8== =%8==

B

&

&.3

&.6

&.9

1.2

1.#

Delt E8 (:!?!:i)

17$&& 2&$&& 23$&& &2$&& $&& &/$&&

i:e

***********

*

**************** 8l5ebo

il!lipti

,el

l et l. + Cli Eo5riol ,etb 92$12"92&&7


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#dopted from ;sposito ,-:,01$

2. randomised controlled trials included= ith a total of +*=1*0 patients 5alogliptin= n?$2@0> linagliptin= [email protected]> saAagliptin= n?+0$+> sitagliptin=n?1$+@> !ildagliptin= n?.+.06

Baseline "b#$c of the studies ranged from 2)+ to @)0) (ean baseline "b#$c= eighted b' sample sie= as .)*0 5ranging from 2)@- to .)$,6)"b#$c !alue= used to adjust b' baseline "b#$c= as .)*

ther meta anal'ses including !ildagliptin are a!ailable 5e)g) Fakhour' D


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Liu et l. Dibete Obe ,etb 1"$/1& 2&12

EPP%, inhibitors

)is7 for hypoglycemia

Placebo%controlled change in "b#$c

Cddsratio

*). *)@*)2

Sulphon'lureasPlacebo

Basal insulin

THE #GIs

GJP%$ Biphasic insulin

Glinides

*)2 *). *)2 $)* $)$

Gliptins# 'ery (o" ris) of

*ypoglycemia


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:ery low ris7 for hypoglycemia by

vildagliptin

!ildagliptin

glimepiride

A*r4 et l. Dibet *er #$"#9 2&1"


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#lucose&mmol(2'

F=

?F>

?F=

!F>

!F=

1F>

1F=

Stop secrete insulin from the K%cells

Stimulate li!er glucose release

Defence

ympatheticnerves

Adrenaline

Cortisol#H

#lucagon

Hypoglycemia defence

;Lects of !ildaglipti

A*r4. 5 Helt* 0i? ,! 9$1## 2&13

ag pt n n ts g ucagon at


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Hypo Eu Hyper#lucose

#lucagonresponse

high

normal

low

Control

Control

:ildagliptin

:ildagliptin

ag pt n n ts g ucagon athigh glucose

and increases glucagon at lowglucose

Ahrn, et al. J Clin Endocrinol Metab 941!"#, !$$9

#20-1

#$0


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Gliptins# %ore than GlucoseControl

(ipids %onami et al+ Adv Ther, -an, .0.

%Gliptins ha!e been reported to reduce cholesterol=but results ha!e been inconsistent)

%(onami et al meta%anal'sis shos that treatmentith EPP%, inhibitors is associated ith a signiMcantreduction in total cholesterol 5%*)$. %*)+@> %*)*-O

mmolJ 5%2)* %$$)+> %+)1*O mgdJ6> P?*)**+6)


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Eiabetes associated ith increased risk offractures

Pioglitaone reduces bone densit' and isassociated ith increased risk of fractures

Insulin associated ith fractures possibl'

because of increased risk of h'pogl'cemiaand falls)


Bone *ealth


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GJP%$ induces osteoblast diLerentiationand inhibits osteoclastic acti!it')

GJP%$ receptor agonists ha!e been shon

to stimulate bone formation in rodents ) ;Aperimental data in animal models

suggest that gastric intestinal pol'peptide5GIP6 is also capable of increasing bonedensit')

$ncretins and GoneDensity


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D00i and 9ractures8%eta1Analysis

Monami et al. Diabetes Care 34:24742476, 2011Diabetes Care 34:24742476, 2011


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Blood Pressure+,%eek multicenter= randomied= double%blind placebocontrolled stud' comparing !ildagliptin 51* mg d or bid6

to placebo Drug/placebo Mean reduction in

systolic blood pressure(mmHg)

Mean reduction in

diastolic blood pressure(mmHg)

Vildagliptin 50 mgN=17

! 0"#

Vildagliptin 100 mg

N=17$

%"5 !"!

&laceboN=175

0"# 0"1

"athwani et al, !==<


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Brain

Shannon et al. Diabetes, 2013


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Cardiovascular 2afety

(onami et al== Eiabetes bes (etab $1:$$


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Met the ri&ar' (a)et' obecti+e o) non

in)eriorit' -H $.9/0 9% C2 $./9 3 1.$/

Long-term cardiovascular outcomes trials withDPP-4 inhibitors

CA0OLNA 5ina6litin +(. 6li&eiride

Mean 73/ ', #$$$ (8bect(

All trial( are rando&i(ed,

do8bleblind, &8lticentretrial( +(. lacebo, 8nle((

otheri(e (tated

ECOS :ita6litin

; to ', 14,$$$ (8bect(

!$$/ !$1$ !$1! !$14 !$1# !$1/

SAO0 :aa6litin; to 4 ', 1#,$$ (8bect(

Objectives =o deter&ine the lon6ter& e))ect o) ??4 inhibitor on C@ o8tco&e( and other

clinicall' rele+ant e+ent( in atient( ith =! at hi6h ri( o) C@

Primary endpoints =i&e to )ir(t occ8rrence o) a ri&ar' C@ e+ent C@ death, non)atal &'ocardial

in)arction or non)atal (troe

EFA,NE Alo6litin

; to ', 4$$ (8bect(

Met the ri&ar' (a)et' obecti+e

o) nonin)eriorit' -H $.9#0 9%

;C5 1.1#

Met the ri&ar' (a)et' obecti+e o) non

in)eriorit' -H 1.$0 9% C2 $./9 1.1!


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$ncidences and odds ratios foradudicated CC: events by treatment

Meta-analysis of vildagliptin >= mg bid data vs all comparators according to themethodology set by the . 9ood and Drug Administrationb>= mg bid odds ratio I=F% &>B C$ =F

)eferencea

n ( " &B'M-H ))&>B C$'

:ilda >= mg

Kd

1= ( 1??

&=F@!'

1 ( 1>>>

&=F='

=F%% &=F?@

!F11'

:ilda >= mgbid

%1 (

ece&ber !$$/:cheiDer A, et al. iabete( Ibe( Metab. !$1$01!4/394

=F=1 1 1===F1 1=

:ildagliptin better:ildagliptin worse

)is7 ratio


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:ildagliptinn(" &B'

Comparators

n(" &B'

M-H ))&>B C$'

:ildagliptin>= mg KFdF(bFiFdF

1(>&=F?'

?!(@1=!&=F>'

1F=% &=F1&=F@%'

1F1 &=F


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#20-1 receptor agonists

Metformin

ulfonylurea

0ioglita*one

D00- inhibitors

$nsulin

Acarbose

#2T-! inhibitors

(imitations "ith some therapies in management of T.Din renal impairment

)enal function

"ormal Mild )$ Moderate evere Termin

#9) &m2(min' L=


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EPP%, inhibitor use in renalimpairment 58I6

!> mg oFdF 1!F> mg oFdF mg oFdF

itagliptin1

D00- inhibitors

1== mg oFdF >= mg oFdF !> mg oFdF

aNagliptin!

Alogliptin?

> mg oFdF2inagliptin

:ildagliptin> >= mg oFdF>= mg bFiFdF

Creatinine

Clearance&m2(min'

erumCreatinine Male&mg(d2'

erumCreatinine

9emale &mg(d2'

?=

?F=

!F>

Mild )$ Moderate )$ evere )$

>=

1F@

1F>

!F> or > mg oFdF !F> mg oFdF

o)d) ? once dail'b)i)d)? tice dail'

$) #!ailable at: http:)merck)comproductusapicircularsjjanu!iajanu!iapi)pdf> +) #!ailable at: http:$)astraeneca%us)compipiongl'a)pdfUpage?$>

0) #!ailable at: http:general)takedapharm)comcontentMle)aspAVFileT'peCode?N;SIN#PI&cache8andomier?2+0-cLb%eb-c%,b*a%ac2@%+-.$*,+1c.@e>,) #!ailable at: http:bidocs)boehringer%ingelheim)comBIDeb#ccessQieSer!let)serVdocBase?renetnt&folderPath?PrescribingWInformationPIsTradjentaTradjenta)pdf>1) #!ailable at: http:)ema)europa)eudocsenGBdocumentlibrar';P#8%ProductInformationhuman***22$DC1***+*0+2)pdf

;!ans (= Eejager S= Scheier #= Fole' ) Is there e!idence of an' safet' diLerences among EPP, inhibitors in thetreatement of people ith T+E and reduced GF8 to chronic kidne' diseaseV Eiabetes Ther 5+*$16-:$%1

:ildagliptin is eKually safe and eOectivein Moderate-evere )$ but with half of

the cost among all gliptins

#djusted mean "b#$c change from baseline to


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SeIere rel i:pir:et

#djusted mean "b#$c change from baseline toeek +, in patients ith moderate or se!ere

renal impairment

il!lipti #& :! J

8l5ebo

,oerte rel i:pir:et

K 1#7 12/

L K 7.9% 7./% K 122 9#

L K 7.7% 7.7%

,e HbA15 5*!e

ro: L to E8

et@ee-

!roup

iere5e

AHu.t

e:e-5*-!e

(%)

AHu.t

e:e-5*-!e

(%)

//

2n atient( ith &oderate renal i&air&ent, (i&ilar roortion( o) tho(e recei+in6 +ilda6litin or lacebo eerienced an' AE -#/ vs7"%, an' :AE -9

vs9%, an' AE leadin6 to di(contin8ation -" vs% or death -1 vs1%. =hi( a( al(o tr8e )or atient( ith (e+ere 2 AE( -7" vs74%, :AE( -19 vs

!1%, AE( leadin6 to di(contin8ation -9 vs#% and death -! vs4%.

* P


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afety in Moderate to evere )enalimpairment

"o deterioration of renal function with vildagliptin

0el i:pir:et ,oerte SeIere

e0 (,D0D) (:L:i1.73 :2)il #&:! J

NK1638l5eboNK129

il #&:! JNK12"

8l5eboNK97

,e elie 39.3 "&.3 21.9 2&.9

,e C*!e ro: belie &./6# &.#72 -1."#6 -1.121,ei C*!e ro: belie -&.&6/ -&.&67 -1.291 -1./72

Eti:te B0 (,D0D) i ptiet @it* eIere :oerte 0 t 2" @?

* eF -MB F e(ti&ated 8(in6 the M )or&8la. a(eline eF i( de)ined a( the

loe(t o) eF -M +al8e( be)ore +i(it ! that ere calc8lated 8(in6 the (er8& creatinine

+al8e be)ore +i(it ! and the a6e at the a((ociated creatinine &ea(8re&ent date

=he o+erall incidence( o) AE(, :AE(, di(contin8ation( d8e to AE( and death( ere

co&arable beteen +ilda6litin $ &6 d and lacebo treat&ent 6ro8(

Go (tati(ticall' (i6ni)icant or clinicall' rele+ant di))erence( )or e+ent( o) identi)ied ri( ob(er+ed

)or +ilda6litin

MDRDB Modi)ication o) iet in enal i(ea(e@. 58a(he+ich1, A. :cheiDer!, K. :hao1, ?.H. Froo",4 L . Nothn'1

Diabetes, Obesity and Metabolism 13: 947954, 2011.


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ignicantly more T!DM patients with severe )$ achieve target HbA1c with vildagliptin compared to sitagliptin

"1Nothn', ol)6an6, et al. OCo&ari(on o) +ilda6litin and (ita6litin in atient( ith t'e ! diabete( and (e+ere renali&air&ent a rando&i(ed clinical trial.ODiabetoloia-!$1 17.

Both treatments ere elltolerated ith similar safet'proMles)

No deterioration of renal

function as obser!ed in an'group)

Co5luio$*i tu proIie urt*er upport or t*e ue o

D88-" i*ibitor i ptiet @it* eIere 0el :pir:et

RCT in 148 patients over 24 weeks

ADA i


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ADA postion statement!=1>

Gliptins#

4avored,2afe till no",

3eal lifeexperience+


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Future Promise


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Gliptins: Ee!eloped & XnderEe!elopment

Qildagliptin

Sitagliptin

SaAagliptin

Jinagliptin

Teneligliptin #logliptin 5FE# #ppro!ed in +*$06

#nagliptin 5#ppro!ed in apan in +*$+6

Gemigliptin 5Being de!eloped b' JG life sciences6

Eutogliptin 5 Being de!eloped b' PhenomiA Corp)6 Phase III Trelagliptin% nce in a eek 5#ppro!ed in apan in +*$16

marigliptin% nce in a Deek 5Being de!eloped b' (erck)6

Currentl' a!ailable in India


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E;pi! role o 8

Baggio J= Erucker E) Biolog' of Incretins: GJP%$ and GIP) Gastroenterolog' +**2>$0+:+$0$+$12


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iit eIer 3 :ot*l

HbA15 7.&% (t@i5e)

S5reei!

il #& :! bi M ,E 1&&& :! bi

il #& :! bi M ,E 1&&& :! bi

# er

M (bl) iuli

M (bl) iuli

At investigator discretion

0u-i$ 3 @?

Period 1 Period 2 Period 3

ilda6litin E))icac' in co&bination ith &et)o0&n or earl

treat&ent o) =!M

0

-o:i=tio-

,E#&&:!D

,E1&&&:!D

,E1#&&:!D

8l5ebo bi M ,E

1&&& :! biil #& :! bi M ,E 1&&& :! bi


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Stud' objecti!es: Primar'

Y No!artis Pharma #G +*$, item code +02+,-

To demonstrate that : the risk of initial treatment failure 5deMned as "b#$c Z

2)*6 is loer ith the combination of !ildagliptin Wmetformin than ith metformin monotherap')

the rate of loss in gl'caemic control o!er time5estimated annualied slope of "b#$c o!er time using arandom coe[cient model6 is loer ith !ildagliptin1*mg bid W metformin than ith metforminmonotherap'

The stu! is positive i"at least one o" theseh!potheses is #et


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Potential implications

Q;8IF\ is the Mrst stud' to in!estigate the long%term clinicalbeneMts of initial combination treatment !ersus the standard%of%care (;T monotherap' folloed b' addition of #E

aressin$ ke! pathoph!siolo$i%al "eatures o" the iseaseat ia$nosis

It ill pro!ide !aluable data on the durabilit' of gl'caemiccontrol= beta%cell function= insulin resistance= safet' andtolerabilit'

It ill eAplore for earl' changes in the !asculature of patientsith T+E( earl' in the course of the disease

&ressin$ pri#ar! %lini%al ob'e%tive "or treat#ent o"

h!per$l!%ae#ia

It has potential to change the a' e treat t'pe + diabetes)

Y No!artis Pharma #G +*$, item code +02+,-


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lipti i 2&1# beo < potetil

be o 5urret reer5*

8reibete

pe 1 ibete

Ee5t o europrote5tio euroe!eertio Diee o il::tio' porii rt*riti l::tor

bo@el iee

tt liIer iee

CrioI5ulr iee


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Basic Succinct Statement % G#JQXS] Presentation: Tablets containing 1* mg of Qildagliptin)

Indications: ^Gal!us is indicated as an adjunct to diet and eAercise to impro!e gl'cemic control in patients ith t'pe + diabetes mellitus 5T+E(6) It isindicated: as monotherap'= in combination ith metformin= hen diet= eAercise and metformin alone do not result in adeuate gl'cemic control= ith

a sulfon'lurea 5SX6= hen diet= eAercise and a SX alone do not result in adeuate gl'cemic control= ith a thiaolidinedione 5THE6= hen diet=eAercise and a THE alone do not result in adeuate gl'cemic control) In triple combination ith a sulfon'lurea and metformin hen diet and eAerciseplus dual therap' ith these agents do not pro!ide adeuate gl'cemic control) Gal!us is also indicated in combination ith insulin 5ith or ithoutmetformin6 hen diet= eAercise and a stable dose of insulin do not result in adeuate gl'cemic control) ^Gal!us is also indicated as initialcombination therap' ith metformin in patients ith T+E( hose diabetes is not adeuatel' controlled b' diet and eAercise alone)

Eosage and administration: ^#dults: The recommended dose is 1* mg or $** mg dail' for monotherap'= and for combination ith metformin= ith aTHE or ith insulin 5ith or ithout metformin6> 1* mg dail' in combination ith a SX> $** mg dail' for triple combination ith metformin and a SX)(aAimum dose is $** mgda' 5in to di!ided doses of 1* mg6)^Children 5under $. 'ears of age6: Not recommended) ^Special population: Inpatients ith moderate to se!ere renal impairment or ;nd Stage 8enal Eisease 5;S8E6= the recommended dose is 1* mg once dail')

Contraindications: "'persensiti!it' to !ildagliptin or to an' of the eAcipients)

Darnings and precautions: ^Gal!us should not be used in patients ith t'pe $ diabetes or for the treatment of diabetic ketoacidosis) ^Not

recommended in patients ith hepatic impairment including patients ith a pre%treatment #JT or #ST_+)1` the upper limit of normal) Ji!er functiontests 5JFT6 to be performed prior to treatment initiation= at three%month inter!als during the Mrst 'ear and periodicall' thereafter) Dithdraal oftherap' ith Gal!us recommended if an increase in #ST or #JT of 0` upper limit normal or greater persist) Folloing ithdraal of treatment ithGal!us and JFT normalisation= treatment ith Gal!us should not be reinitiated) ^Clinical eAperience in patients ith N\"# functional class III treatedith !ildagliptin is still limited and results are inconclusi!e) ^Not recommended in patients ith N\"# Class IQ)

Domen of child%bearing potential= pregnanc': Should not be used during pregnanc' unless the potential beneMt justiMes the potential risk to thefetus)

Breast%feeding: Should not be used)

Special eAcipients: Contains lactose

#d!erse reactions:

^8are cases of angioedema) 8are cases of hepatic d'sfunction 5including hepatitis6 ^(onotherap' % Common: diiness % Xncommon: headache=

constipation= oedema peripheral) ^Combination ith metformin % Common: tremor= diiness= headache) ^Combination ith a sulfon'lurea %Common: tremor= headache= diiness= asthenia) Combination ith a thiaolidinedione % Common: eight increase= oedema peripheral)^Combination ith insulin % Common: headache= nausea= gastrooesophageal reuA disease= chills= decreased blood glucose Xncommon: Eiarrhoea=atulence) ^Combination ith metformin and a sulfon'lurea % Common: diiness= tremor= asthesia= h'pogl'caemia= h'perhidrosis) ^Post%marketingeAperience % 8are: hepatitis 5re!ersible ith drug discontinuation6 Xnknon: urticaria= pancreatitis=bullous and eAfoliati!e skin lesions)

Interactions: ^Qildagliptin has a lo potential for drug interactions) ^No clinicall' rele!ant interactions ith other oral antidiabetics 5glibenclamide=pioglitaone= metformin6= amlodipine= digoAin= ramipril= sim!astatin= !alsartan or arfarin ere obser!ed after co%administration ith !ildagliptin)

Packs: BoA of + strips of $, tablets each

Note: Before prescribing= please consult full prescribing information a!ailable from No!artis "ealthcare Pri!ate limited= Sando "ouse= Er) #nnieBesant 8oad= Dorli= (umbai% ,** *$.= Tel: *++ +,@1 ....

For the use onl' of a registered medical practitioner or a hospital or a laborator')

India BSS dtd $+ #ug +*$, based on international BSS dtd 0* ul' +*$, eLecti!e from $0 ct $,)


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Basic Succinct Statement Gal!us(et]

Presentation: Tablets containing Qildagliptin(etformin h'drochloride MAed dose combination: 1* mg1** mg= 1* mg.1* mg= 1* mg$=***mg)

Indications: ^Gal!us (et is indicated as an adjunct to diet and eAercise to impro!e gl'cemic control in patients ith t'pe + diabetes mellitus

5T+E(6 hose diabetes is not adeuatel' controlled on metformin h'drochloride or !ildagliptin alone or ho are alread' treated ith thecombination of !ildagliptin and metformin h'drochloride= as separate tablets) ^Gal!us (et is indicated in combination ith a sulphon'lurea5i)e)= triple combination therap'6 as an adjunct to diet and eAercise in patients inadeuatel' controlled ith metformin and a sulphon'lurea)^Gal!us (et is indicated in combination ith insulin 5i)e)= triple combination therap'6 as an adjunct to diet and eAercise to impro!e gl'cemiccontrol in patients hen stable dose of insulin and metformin alone do not pro!ide adeuate gl'cemic control) ^ Gal!us (et is also indicatedfor the treatment of T'pe + Eiabetes mellitus ha!ing "b#$c _ . here diabetes is not adeuatel' controlled b' diet and eAercise alone)

Eosage and administration: ^Eo not eAceed the maAimum recommended dail' dose of !ildagliptin 5$** mg6) ^Should be gi!en ith meals)^#dults: Starting dose for patients inadeuatel' controlled on !ildagliptin or metformin h'drochloride monotherap': 1* mg1**mg tice dail'and graduall' titrated after assessing adeuac' of therapeutic response) ^Starting dose for patients sitching from combination therap' of!ildagliptin plus metformin h'drochloride as separate tablets: 1* mg1** mg= 1* mg.1* mg or 1* mg$=*** mg based on the dose of!ildagliptin or metformin alread' being taken) ^Starting dose for treatment na!e patients: ma' be initiated at 1* mg1** mg d and

graduall' titrated to a maAimum dose of 1* mg$=*** mg bid after assessing adeuac' of therapeutic response) ^Xse in combination ith asulfon'lurea or ith insulin: the dose of Gal!us (et should pro!ide !ildagliptin dosed as 1* mg tice dail' 5$** mg total dail' dose6 and adose of metformin similar to the dose alread' being taken) 8enal impairment: Eosage adjustment ma' be reuired in patients ithcreatinine clearance beteen -* and @* mlmin) ^Geriatric patients: Eosage should be adjusted based on renal function ^Children 5under $.'ears of age6: Not recommended)

Contraindications:


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Domen of child%bearing potential= pregnanc': Should not be used in pregnanc' unless the potential beneMt justiMes the potentialrisk to the foetus)

Breast%feeding: Should not be used during breast%feeding)

#d!erse reactions:

^Qildagliptin: 8are cases of angioedema) 8are cases of hepatic d'sfunction 5including hepatitis6) ^Qildagliptin monotherap' %Common: diiness Xncommon: headache= constipation= oedema peripheral) ^(etformin monotherap' Qer' common: loss ofappetite= atulence= nausea= !omiting= diarrhoea= abdominal pain) Common: d'sgeusia) Qer' rare: lactic acidosis= hepatitis= skinreactions such as er'thema= pruritus and urticarial= decrease of !itamin B$+ absorption= li!er function test abnormalities) ^thereLects ith combination of Qildagliptin and (etformin % Common: tremor= diiness= headache) ^ther eLects ith combinationof Qildagliptin and (etformin ith insulin Common: headache= nausea= gastrooesophageal reuA disease= chills= blood glucosedecreased Xncommon: diarrhoea= atulence) ^ther eLects ith combination of Qildagliptin and (etformin ith a sulfon'lurea Common: diiness= tremor= asthenia= h'pogl'cemia= h'perhidrosis) Post%marketing eAperience: % 8are: hepatitis 5re!ersibleith drug discontinuation6 % Xnknon: urticaria= pancreatitis=bullous and eAfoliati!e skin lesions)

Interactions: ^Interactions ith Qildagliptin: lo potential for drug interactions= no clinicall' rele!ant interactions ith other oralantidiabetics 5glibenclamide= pioglitaone= metformin6= amlodipine= digoAin= ramipril= sim!astatin= !alsartan or arfarin ereobser!ed after co%administration ith !ildagliptin) ^Interactions ith metformin h'drochloride: furosemide= nifedipine= cationicdrugs= drugs tending to produce h'pergl'cemia= alcohol)

Packs: BoA containing - strips of $* tablets each

Note: Before prescribing= consult full prescribing information a!ailable from No!artis "ealthcare Pri!ate Jimited= Sando "ouse=Er) #nnie Besant 8oad= Dorli= (umbai% ,** *$.= Tel: *++ +,@1 ....

For the use onl' of a registered medical practitioner or a hospital or a laborator')

India BSS dtd $+ #ug +*$, based on international BSS dtd 0* ul' +*$,= eLecti!e from $0 ct $,

i5 Su55i5t Stte:et < lIu,et


46/46

EisclaimerThe !ies= opinions= ideas etc eApressed therein are solel' those of the author)

No!artis does not certif' the accurac'= completeness= currenc' of an' information andshall not be responsible or in an'a' liable for an' errors= omissions or inaccuracies insuch information) No!artis is not liable to 'ou in an' manner hatsoe!er for an'decision made or action or non%action taken b' 'ou in reliance upon the informationpro!ided) No!artis does not recommend the use of its products in unappro!edindications and recommends to refer to complete prescribing information prior to usingan' of the No!artis products)

Issued in scientiMc ser!ice to medical professionals

(or "ull prou%t in"or#ation please write to )

No!artis "ealthcare Pri!ate Jimited=

Sando "ouse= 2th oor=

Shi!sagar ;state= Er) #nnie Besant 8oad=

Dorli= (umbai= ,** *$.= INEI#

Gliptins- Evaluation

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