Actualitésdans le diabète de type2: Les inhibiteurs de la DPP-4

5/26/2018 Actualitsdans le diabte de type2: Les inhibiteurs de la DPP-4

1/81

Actualitsdans le diabte de type2:

Les inhibiteurs de la DPP-4Pr Ag Fatma MNIF BOUSSARSAR

Service dEndocrinologie-Diabto lo gie SFAX

Sfax 17 Mai 2014

CHU Hdi CHAKER SFAX

UR04SP31Obsit-Sd Mtabolique


2/81

The Diabetes Epidemic: Global Projections,20102030

IDF. Diabetes Atlas 5thEd. 2011


3/81

TUNISIA

8.5%, 2010

Growing to

11%, 2030


4/81

Impact de la Thrapie Intensive du Diabte:Rsum des Etudes Cliniques Majeures

Study Microvasc CVD MortalityUKPDS

DCCT / EDIC* ACCORD ADVANCE

VADT Long Term Follow-up

Initial Trial

* in T1DM

Kendall DM, Bergenstal RM. International Diabetes Center 2009

UK Prospective Diabetes Study (UKPDS) Group.Lancet1998;352:854.Holman RR et al.N Engl J Med. 2008;359:1577. DCCT Research Group. N Engl J Med 1993;329;977.

Nathan DM et al.N Engl J Med. 2005;353:2643. Gerstein HC et al.N Engl J Med.2008;358:2545.Patel A et al.N Engl J Med 2008;358:2560. Duckworth W et al. N Engl J Med 2009;360:129. (erratum:Moritz T.NEnglJMed2009;361:1024)


5/81

Pour rduireles complications

Diminuer

le taux dHbA1c

Sans augmenter

les hypoglycmies

Pour amliorer laqualit de vie

Objectifs glycmiques


6/81

FPG


7/81

a

HbA1c 6.5%.Liebl A, et al. Diabetologia.2002; 45: S23S28.

In the CODE study of a European cohort of over 7000 patients withT2DM, ONLY31% of patients had adequate glycaemic control

Patients

withadequateglycae

mic

control(%)

Approximately 70% of patients with T2DM do not reach

HbA1c goalsa


8/81

100%

HbA1c


9/81

Tunisie

Nbre dHbA1c/ an 2.5 1.1

HbA1c (moyenne) 9.4 2.1

>9 %

< 7%(ADA)

< 6 %(IDF)

36 %

15.2 %

7.8%

Diabcare Tunisie 2008 (5 Centres Hospitaliers)


10/81


11/81


12/81


13/81

Pre-

Diabetes

Type 2 diabetes

Years fromdiagnosis

0 5-10 -5 10 15

Pre-diabetes

Onset Diagnosis

Insulin secretion

Insulin resistance

Post-Meal glucose

Fasting glucose

-Cell function

Prog ressiv e -Cell Failure

Evolution naturelle du DT2


14/81T2DM Antihyperglycemic Therapy: General RecommendationsDiabetes Care,Diabetologia. 19April 2012

E ub ahead of rint



E ub ahead of rint


17/81

Diabetes Care,Diabetologia.

19April 2012 [Epub ahead of print]


18/81

ADA-EASD Position Statement: Management of

Hyperglycemia in T2DM

Options thrapeutiques

Anti diabtiques Oraux et Injectables non

insuline:

-Metformine

-Sulfonylures

-Thiazolidinediones

-Inhibiteurs de la DPP-4

-Agonistes des rcepteurs GLP-1

-Meglitinides

-Inhibiteurs -glucosidase

-Sequestrants acides biliaires

-Agonists Dopamine-2

-Amyline mimetiques

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

Incrtines

D b


19/81

18/05/2014

Grle

Vidange gastrique

acclre Deficit dInsulinoscretion

prcoce

Glucose

Scretion excessive de

Glucagon

Captation insuffisante par le muscle

Libration excessive dAG

Production excessivede Glucose

Diabte type 2

D l h h l d l l


20/81

De la physiopathologie dcoule les principauxmodes dactiondes A.D.O

18/05/2014

Diabetes Obes Metab 1999

Grle

Deficit dInsulinoscretion

Glucose


glucagon

Sulphonylures

Glinides

Inhibiteurs de la-glucosidase

GLP1

Inhibiteurs DDPIV


21/81

18/05/2014

Diabetes Obes Metab 1999

Grle

Deficit dInsulinoscretion

Glucose


glucagon

Nouveaux mdicaments du diabte de type 2

Les IncretinesAnalogues du Glucagon Like Peptide 1 (GLP-1)Inhibiteurs DDPIV

LES INCRETINES

Analogues deGLP1

Inhibiteurs DDPIV


22/81

Inhibiteurs de la DPP4+ Metformine; autres combinaisons

Inhibiteurs de la DPP4: Indications

Incrtines / Inhibiteurs de la Di-Peptidyl Peptidase - 4 :

Mode daction

Sommaire

Inhibiteurs de la DPP4:Profil de tolrance

Inhibiteurs de la DPP4 et Ramadan


23/81

Inhibiteurs de la DPP4+ Metformine; autres combinaisons



Mode daction

Sommaire




Mode daction


24/81

Intestine Secretion

Insulin

Dfinition de leffet incrtine

In cret in


25/81

Intestin

Scrtion

dhormones

incrtines

Cellules K GIP

Cellules L GLP-1

Le pancras est

un organe cibledes incrtines

Effet incrtine :

Amplification de

linsulino-scrtion

Cellule Cellule a

Incrtines

Insuline

Glycmie

Glucagon

Glycmie

Glycmie constante1 g/l

AlimentationGLP-1 (x 6 8) libration dinsuline

Leffet incrtine

Mise en vidence de leffet incrtine chez le sujet


26/81- -

Mise en vidence de l effet incrtine chez le sujet

non diabtique

010

10

15

20

glycmie(mmol/L

)

5

60 120 180

Temps (min)

0

40

60

80

nsulineIIR(mU/L)

20

5 10 60 120 1805

** * * * * *

Effet incrtine

Glucose per os

Perfusion isoglycmique de

glucose IV

Temps (min)

Adapt de Nauck M et al. Diabetologia. 1986;29:4652.

* p0.05

70% de la scrtion dinsuline en rponse un repas estlie leffet incrtine

Effet incrtine = Insulinoscrtion en rponse au glucose oral significativement

suprieure celle obtenue en rponse au glucose administr par voie IV

Altration de leffet incrtine chez les sujets


27/81- -

glycmie(mmol/L) Sujets contrls Diabtiques de Type 2

Altration de leffet incrtine chez les sujets

diabtiques de type 2

Adapt de Nauck M et al. Diabetologia. 1986;29:4652.

0

10

10

15

20

5

60 120 180

Temps (min)

0

40

60

80

InsulineIR(mU/L)

20

0

10

15

20

glucoseplasmatiqu

e

(mmol/L)

5

Temps (min)

0

40

60

80

Insuline(mU/L)

20

5 10 60 120 1805

10 60 120 1805 10 60 120 1805

* * * * * * * **

*

Effetincrtine normal

Effet

incrtine diminu

Glucose per os

Isoglycmie par glucose IV

* p0.05

L'insuline et le glucagon en rponse aux repas chez des


28/81

-60 0 60 120 180 240

20.0

18.3

16.615.0

13.3

6.1

4.4

140

130120110

100

90

12090

6030

0

Glucose(mmol/l)

Insulin(mU/l)

Glucagon(ng/l)

Meal

Time (min)

Type 2 diabetes

Normal subjects

Delayed/depressed

insulin response

Mller et al. N Engl J Med.1970

Nonsuppressed

glucagon

Normal subects n=11; Type 2 diabetes n=12

L insuline et le glucagon en rponse aux repas chez des

sujets normaux et de diabte de type 2


29/81

Diabte de type 2

Diminution de leffet

incrtine

Associe une rduction

de la scrtion de GLP-1

pendant les repas

et une altration

de lactivit du GIP

Activit du GLP-1 intacte

StimuleScrtion de linsuline Stimule

-Scrtion du glucagon Inhibe

-

-

Prise alimentaire

Vidange gastrique

Rduite

Ralentie

-Synthse de linsuline Stimule

FavoriseProlifration cellulaire Favorise

NormaleScrtion Rduite

AltreActivit Prserve

Actions physiologiques

Diabte de type 2

GIP GLP1

Glycmie constante

1 g/l

Altration de leffet incrtine chez les sujetsdiabtiques de type 2


30/81

Le rle de la dipeptidyl peptidase-IV (DPP-IV)

Adapt de Deacon CF, et al. Diabetes. 1995;44:1126-1131.

GIP et GLP-1 :demi-vie courte

(1 2 minutes

pour le GLP-1)

De laction

de la DPP-IV

+Leur limination

rnale

Inactivation du GLP-1 par la DPP-4

Repas

Synthse

intestinale

de GLP-1

GLP-1 actif

GLP-1

T = 1 2 min

GLP-1 inactif

(> 80 % du pool)

Dgradation

protolytique

(DPP-4)

GLP-1

Extrmit N-terminale

Extrmit C-terminale

Amide


31/81

.

Adapt de Deacon CF, et al. Diabetes. 1995;44:1126-1131.

Inhibiteurs de la DPP-4 : Mode daction

GLP-1

actif

GLP-1

Inactif

(>80% du pool)

GLP1 T1/2= 1 2 min

DPP-4

Inhibiteur DPP-4

GLP-1 endogne :

Restaure la sensibilit

au signal glucoseInsuline

Glucagon

Contrle glycmique

Scrtions

intestinales

Comparaison de la Rponse des cellules au glucose en cas


32/81

Comparaison de la Rponse des cellules au glucose en casdHyper- versus Hypoglycmie avec et sans traitement parinhibiteurs de la DPP4 (la Vildagliptine)

AUC=area under the curve; N=25 (completers population). *P=0.019; **P=0.039.

Ahrn B, et al. Poster 560-P. Presented at: 68th Scientific Sessions of the American Diabetes Association;

June 6-10, 2008; San Francisco, CA;Thornberry NA, et al. Best Pract Res Clin Endocrinol Metab. 2009; 23: 479486.


33/81

La Vildagliptine amliore la masse des cellules du pancras du rat

Duttaroy et al. Diabetes 2005;54(Suppl. 1): A141. Abstract 572P and poster presented at ADA

Vildagliptin

60 mg/kg

21 daysVehicle

Insulin

Replication

-cellMass(mg)

Vehicle Vilda

p


34/81

Pharmacokinetic Properties of DPP-4Inhibitors

Sitagliptin1

(Januvia)

Vildagliptin2

(Galvus)

Saxagliptin3

(Onglyza)

Alogliptin5

(Takeda)

Absorption tmax 14 h 1.7 h2 h (4 h for active

metabolite)12 h

Bioavailability ~87% 85% >75 %4 N/A

Half-life (t1/2) atclinically relevant

dose

12.4 h ~23 h2.5 h (parent)

3.1 h (metabolite)

12.421.4 h(25800 mg)

Distribution 38% protein bound 9.3% protein bound Low protein binding N/A

Metabolism ~16% metabolized

69% metabolized

mainly renal

(inactive metabolite)

Hepatic

(active metabolite)

CYP3A4/5


35/81

IDPP4+ Metformine chez le patient insuffisamment

contrl par la Metformine seule; autres combinaisons

Inhibiteurs de la DPP4 : indications


Mode daction

Sommaire




36/81

T2DM Antihyperglycemic Therapy: General RecommendationsDiabetes Care,Diabetologia. 19April 2012

E ub ahead of rint


37/81


E ub ahead of rint

Facilit dutilisation

Pas deffets secondaires

Pas dhypoglycmies


38/81

T2DM Anti-hyperglycemic Therapy: General Recommendations Diabetes Care,Diabetologia. 19April 2012[Epub ahead of print]


39/81

Adapted Recommendations: When Goal is to Avoid Weight Gain Diabetes Care,Diabetologia. 19April 2012[Epub ahead of print]


40/81

Adapted Recommendations: When Goal is to Avoid Hypoglycemia Diabetes Care,Diabetologia. 19April 2012[Epub ahead of print]


41/81


E ub ahead of rint

Si Metformine maltolre ou contreindique

Sitagliptin Consistently and Significantly Lowers A1C


42/81

42

Sitagliptin Consistently and Significantly Lowers A1CWith Once-Daily Dosing in Monotherapy

*Between group difference in LS means.

Raz I et al; PN023; Aschner P et al. PN021; Nonaka K et al; A201. Abstracts presented at: 66thScientific Sessions of the AmericanDiabetes Association; June 9-13, 2006; Washington, DC.

Change vsplacebo*

Placebo (n=74)

Sitagliptin 100 mg (n=168)

Time (wk)

18-Week study

0 6 12 18

A1C(%)

7.2

7.6

8.0

8.4

-0.6%(P


43/81

IDPP4 + Metformine chez le patient insuffisamment




Mode daction

Sommaire


Inhibiteurs de la DPP4: Profil de tolrance


44/81

Initial Combination Therapy with Sitagliptin andMetformin: Effective and Durable Glycemic ControlOver 1 Year in Patients With T2DM

23

41

25

35

44

57

48

6367

77

0

10

20

30

40

50

60

70

80

90

Week 54 CompletersAPT

Proportionofpatie

nts(%)

Proportion of patientsachieving an A1C target of


45/81

Initial Combination Therapy with Sitagliptin andMetformin: Change From Baseline in A1C at Week 54by Baseline A1C Subgroups*

10%(mean 10.4%)

9% and


46/81

Incidence of Hypoglycemia With Sitagliptin WithMetformin Was Similar to Placebo With

Metformin

24 Week Add on Therapy to Metformin Study

All-patients-as-treated populationaSitagliptin 100 mg/day; bMetformin 1500 mg/day

Adapted from Charbonnel B et al. Diabetes Care.2006;29:26382643.

Patients with at least one episode of hypoglycemia over 24 weeks

Patients(%)

Placebo + metforminb(n=237)

Sitagliptina+ metforminb(n=464)

2.1%

1.3%

0.0

1.0

2.0

3.0

4.0

5.0

24-Week Add-on Therapy to Metformin Study


47/81

Sitagliptin With Metformin Provided WeightLoss Similar to Placebo With Metformin at Week24

ee dd o e apy to et o Study

aExcluding data after initiation of glycemic rescue therapy; bleast squares means;cSitagliptin 100 mg/day; dMetformin 1500 mg/day

Adapted from Charbonnel B et al. Diabetes Care.2006;29:26382643.

0.6P=0.017

vs baseline0.7

P


48/81

Initial Fixed-Dose Combination Therapy With Sitagliptin+ Metformin vs Metformin Monotherapy: Study Design

Day 1

RandomizationWeek 44

Screening

periodPhase A Phase B

Screening

1 week 18 weeks

aMetformin was initiated at 500 mg bid and titrated up to 1000 mg bid over 4 weeks. Patients who were unable to tolerate the

maximum dose of sitagliptin/metformin FDC or metformin were allowed to be down-titrated to a minimum dose of

sitagliptin/metformin FDC 50/500 mg bid or metformin 500 mg bid.

bid=twice daily; FDC=fixed-dose combination; OHA=oral antihyperglycemic agent; qd=once daily; R=randomization; T2DM=type 2

diabetes mellitus.

1. Reasner C et al. Poster presented at: American Diabetes Association 69th Scientific Sessions. New Orleans, LA. June 59, 2009.2. Data on file, MSD.

R

26 weeks

Week 18

T2DM, aged

1878 yrs,

Off OHA

4 months,

HbA1c

7.5%

Sitagliptin 50 mg bid + metformin 1000 bida (n=626)

Metformin 1000 mg bida (n=624)

C S


49/81

Initial Fixed-Dose Combination Therapy With Sitagliptin+ Metformin vs Metformin Monotherapy: HbA1cResultsOver 18 Weeks

HbA1cLSMean(SE)

C

hangeFromB

aseline,%

Week

Sitagliptin/metformin FDC (n=560)

Mean baseline HbA1c=9.9%

Metformin (n=566)

Mean baseline HbA1c=9.8%

LS means

difference

0.6; P


50/81

Initial Fixed-Dose Combination Therapy With Sitagliptin +Metformin vs Metformin Monotherapy: Change from Baseline inHbA1cby Baseline HbA1c

at Week 18

FAS=full analysis set; FDC=fixed-dose combination.

1. Reasner C et al. Poster presented at: American Diabetes Association 69th Scientific Sessions. New Orleans, LA. June 59, 2009.2. Data on file, MSD.

HbA1cLSMeanChange

fromBaseline,%

Baseline HbA1c,%


51/81

Sitagliptin Add-on to Metformin Improved 24-HourGlucose Profile in Patients With Type 2 Diabetes

Post Prandial

Fasting/Pre-Prandial

Vild li ti tf i bi t l


52/81

Vildagliptine + metformine: bien tolre

AE=adverse event.

Only data using the marketed regimen of vildagliptin are shown.Bosi E, et al. Diabetes Care.2007; 30: 890895.

Vildagliptin

50 mg twice daily

+ metformin

(n=183), n (%)

Placebo+ metformin

(n=181), n (%)

Any AE 119 (65.0) 115 (63.5)

Any gastrointestinal AE 27 (14.8) 33 (18.2)

Upper respiratory tract infection 14 (7.7) 16 (8.8)

Dizziness 11 (6.0) 7 (3.9)

Nasopharyngitis 11 (6.0) 13 (7.2)

Influenza 10 (5.5) 11 (6.1)

Diarrhoea 8 (4.4) 10 (5.5)

Nausea 8 (4.4) 9 (5.0)

Pain in extremity 8 (4.4) 6 (3.3)

Headache 7 (3.8) 6 (3.3)

Vild li ti SU i l tf i


53/81

Vildagliptine vs SU associe la metformine:design de ltudeet objectifs

Objective:demonstrate long-term efficacy and safety of vildagliptin vs glimepiride

as add-on to metformin

Target population:patients with T2DM inadequately controlled on stable metformin monotherapy(metformin minimum dose 1500 mg/day; HbA1c 6.58.5%)

Design:double-blind, randomised, multicentre, active-comparator, 104-week study

n=1556: Glimepiride up to 6 mg once daily + metformin

n=1562: Vildagliptin 50 mg twice daily + metformin

4 weeks

Metformin

*Randomised population.

HbA1c=haemoglobin A1c; SU=sulfonylurea; T2DM=type 2 diabetes mellitus.Matthews DR, et al. Diabetes Obes Metab.2010; 12: 780789.

3118*

104 weeks

Vildagliptine: aussi efficace que glimepiride


54/81

39

600

500

400

300

200

100

0

NI=non-inferiority

Ferrannini et al. Diabetes Obes Metab 2009;11:15766

Data on file, Novartis Pharmaceuticals

Vildagliptin 50 mg twice daily + metforminGlimepiride up to 6 mg once daily + metformin

Duration: 52 weeks

Add-on to metformin: vildagliptin vs glimepiride

Time (weeks)

Mean

HbA1c(%)

NI: 97.5%

CI (0.02, 0.16)

0.4%

0.5% In

cidence(%)

1389 1383n=

No

.ofevents

1389 1383n=

No

.ofevents

1389 1383n=

Time (weeks)

Bodywei

ght(kg)

1.8 kgdifference

g p q g passocis la metformine 52 semainesans prise de poids et avec moins dhypoglycmies

7.5

7.3

7.1

6.9

6.7

6.5

84 0 4 8 12 16 20 24 28 32 36 40 44 48 52 56

20

15

10

5

0

1.7

18.2 554 12

10

8

6

42

00

10

91.0

90.5

90.0

89.589.0

88.5

88.0

87.5

8 4 0 4 8 12 16 20 24 28 32 36 40 44 48 52

Severe events(grade 2 and

suspected grade 2)

Number ofhypoglycemic

events

Patients with

1 hypos (%)

Add-on treatment to metformin

(~1.9 g mean daily)


55/81

55 Author | 00 Month YearSet area descriptor | Sub

level 1


56/81


level 1


57/81


level 1


58/81


level 1


59/81


level 1


60/81


level 1


61/81

66 Author | 00 Month YearSet area descriptor | Sublevel 1

Additi f Sit li ti t I li Th


62/81

Addition of Sitagliptin to Insulin Therapy:Study Design

Single-bl indplacebo run- in

per iod

Continue on a stable dose ofinsulin with or without metformin

Begin single-blind run-in period

Randomization Week 24

24-Week Stable Insu l in Do se Period

QD=daily.T. Vilsbll et al. Diabetes, Obesity and Metabolism 12: 167177, 2010.

Patients with type 2 diabetes

Age >21 years

Receiving insulin (includingglargine, detemir, ultralente, NPH,lente, or premixed insulin) aloneor with metformin 1500 mg/day

Not receiving premeal short-

acting insulin HbA1c7.5% and 11%

Placebo (n=319)

Sitagliptin 100 mg QD (n=322)

R

Screening

visitWeek2

Addition of Sitagliptin to Insulin Therapy:


63/81

0 6 12 18 24

0.1

Addition of Sitagliptin to Insulin Therapy:HbA1cChange From Baseline Over Time

aBaseline mean HbA1c: 8.72% for sitagliptin, 8.64% for placebo

FAS=full analysis set; LOCF=last observation carried forward; LS=least squares; SE=standard error.T. Vilsbll et al. Diabetes, Obesity and Metabolism 12: 167177, 2010.

FAS Population (LOCF)

Placeboa

Sitagliptina

Difference =0.56%

(P


64/81


contrl par la Metformine seule et autres combinaisons



Mode daction

Sommaire

Inhibiteurs de la DPP4 : Profil de tolrance


Inhibiteurs de la DPP4: profil de tolrance tendu


65/81

Inhibiteurs de la DPP4: profil de tolrance tendu

Les inhibiteurs de la DPP4 ont dmontr un bon profil descurit et de tolrance

>11,500 patients en 38 tudes de Phase II et III * traverstout le monde(mis part le Japan) traits par vildagliptine oubien par lassociationfixe vildagliptine + metformine

>1.2 million patient-trait par an dexposition la vildagliptineou bien lassociationfixe vildagliptine + metformine(post-

marketing exposure)

*Treatment duration ranked from 12 to >104 weeks.a

As of March 2010 ;b

As of January 2011;

Data on file. Novartis Pharma AG, Basel, Switzerland. 2010.

Scurit et Efficacit chez linsuffisant


66/81

rnal 52 semaines

52 week AE renal study

Moderate RI

Results:

50 mg qd Placebo

122 76

94 64

# of Patients

Severe RI

Safety profile similar to placebo

Clinically significant decrease in HbA1c

Diabetes Obesity and Metabolism 2012

epub ahead of print


67/81

IDPP4: Contre indications Prcautions demploi


68/81

IDPP4: Contre indications- Prcautions d emploi

Pas dutilisation dans les cas suivants : Grossesse et lallaitement

Insuffisance cardiaque de classe III ou IV (classificationNYHA)

Insuffisance hpatique et/ou si lvation des

transaminases > 3 x LSN* avant traitement pour la

Vildagliptine

Chez le patient diabtique de type 1 ou pour le traitement

de lacidoctose diabtique.

Contre-indiqu : en cas dhypersensibilit la substance active ou lun des excipients

Utilisation avec prudence : Chez le patient sous hmodialyse prsentant une

insuffisance terminale.

Chez le patient prsentant une insuffisance cardiaque de

classe I et II.

Vildagliptine :inhibiteur de la DPP 4 indiqu chez
http://b2.img.v4.skyrock.net/b28/nicofendt936/pics/1700974154.jpg


69/81

38 Ph2/Ph3 of >8,000 patientsand studies with 301 patients 75

year between 12-104 weeks.

Only DPP4 inhibitor withoutcautionary label for patients > 75

years in EU.EU.

Diabetes Obesity and Metabolism 13: 55-64, 2011

Vildagliptine :inhibiteur de la DPP4 indiqu chez

le DT2 75 ans .Sans restrictions demploien Europe

Vildagliptine + metformine: une rduction de1 1% dHbA1c chez les DT2 75 ans


70/81

1.1% dHbA1c chez les DT2 75 anssans hypoglycmie ni prise de poids

Overall AEs, drug-related AEs and SAEs were all reported with a lower frequency in elderly patients receiving vildagliptin (133.9, 14.5 and 8.8 events per

100 SYE, respectively) than in elderly patients receiving comparators (200.6, 21.8 and 16.5 events per 100 SYE, respectively), and the incidence of

discontinuations due to AEs was similar in the 2 treatment groups (7.2 vs 7.5 events per 100 SYE, respectively). The incidences of AEs, drug-related AEs,

SAEs and discontinuations due to AEs were overall comparable between younger and older patients. The most notable difference was a higher incidence

of SAEs in the comparator group in patients 75 years vs


71/81

Inhibiteurs DPP4

*Bnfices et risques cardiovasculaires au long

cours non encore tudis

*Plusieurs tudes :

TECOS : sitagliptine

CAROLINA : linagliptine

SAVOR /: saxagliptine

EXAMINE : alogliptine

Curr cardio rep 2013) 15, 327 -3-9

Et d SAVOR / li ti


72/81

Etude SAVOR /: saxagliptine

n engl j med 369;14 nejm. october 3, 2013

*16492 diabtiques haut risque cardiovasculaire

*TTT par saxagliptine / placebo

*Suivi 2,1ans

Et d EXAMINE / Al li ti


73/81

n engl j med 369;14 nejm.org october 3, 2013

*5380 diabtiquesayant eu un IDM ou

SCA dans les derniers

15-90jours

*TTT par alogliptine /

placebo

*Suivi 40 mois (18mois en moyenne )

Etude EXAMINE /: Alogliptine



74/81


n engl j med 369;14 nejm.org october 3, 2013

Mortalit toutes causes Mortalit cardio vsx

C i l t lit d l i ti


75/81

GRAIG CURRIE EASD sep 2013

Comparaison sur la mortalit de lassociation

Met + Sulf / Met +DPP4-i

Sommaire


76/81

Inhibiteurs de la DPP4 : Profil de tolrance




Mode daction

Inhibiteurs de la DPP-IV et Ramadan

Inhibiteurs de la DPP4: indications

Ramadan


77/81

Ramadan

J-45

Effets de la Vildagliptine chez le DT2 qui jene


78/81

Effets de la Vildagliptine chez le DT2 qui jene

VECTOR: pas dhypoglycmiessous


79/81

Vildagliptine

Mean between-group difference in patientswho experienced at least one HE was41.7% (P=0.0002)

*Mean between-group difference (vildagliptin cohort minus SU cohort) in the number of

HEs:0.9 (95% CI1.5,0.4) (P=0.0013)

Mean between-group difference (vildagliptin cohort minus SU cohort) in the number of

severe (grade 2) HEs: 0.0 (95% CI0.1, 0.0) (P=0.4289) Hassanein M, et al. Curr Med Res Opin.2011; 27: 1367-1374

HEs*

Experienced 1 eventMean (SD)

Range

95% CI

Total

Severe (grade 2) HEs

Experience 1 eventMean (SD)

Range

95% CI

Total

00.0 (0.0)

0

(0, 0)

0

0

0.0 (0.0)

0

(0, 0)

0

150.9 (1.3)

0-4

(0.5, 1.4)

34

1

0.0 (0.2)

0-1

(0.0, 0.1)

1

Vildagliptin cohort

n=23

SU cohort

n=36

VECTOR: HbA1c and Observance


80/81

VECTOR: HbA1c and Observance

Vildagliptin significantly lowered

HbA1c (7.7% to 7.2%) vs SU

(7.2% vs 7.3%) post-Ramadan. Between-

group difference 0.5% (P=0.0262)

Hassanein M, et al. Curr Med Res Opin.2011; 27: 1367-1374

+0,1%-0,4%

-0,5%


81/81

Merci

Actualitésdans le diabète de type2: Les inhibiteurs de la DPP-4

Documents

Transcript of Actualitésdans le diabète de type2: Les inhibiteurs de la DPP-4