ueda2016 symposium - managing special population in diabetic patient,vildagliptin evidence - ayman...

Managing special population in diabetic patient ...

Vildagliptin Evidence

Ayman El Sebaie, MRCP(UK)

Head of Nephrology & Endocrinology

Department

IMC

Diabetes is a huge and growing problem, and the costs to society are high and

escalating

IDF Diabetes 6th Atlas. International Diabetes Federation.http://www.idf.org/diabetesatlas. Accessed Nov 19th, 2013

Worldwide prevalence of diabetes is high and is expected to increase to 592 million

by 2035

IDF Diabetes 6th Atlas. International Diabetes Federation.

http://www.idf.org/diabetesatlas. Accessed Nov 19th, 2013

Agenda

• Vildagliptin with renal impairment patients

• Vildagliptin with elderly and very elderly population

• Vildagliptin safety

CHF = Congestive Heart Failure; ESRD = End-Stage Renal Disease; MI = Myocardial Infarction; TIA = Transient Ischemic Attack

Adapted from http://www.eatlas.idf.org/complications Accessed August 15, 2005

Eyes

(retinopathy, glaucoma,

cataracts)

Brain and Cerebral

Circulation

(stroke, TIA)

Heart and Coronary

Circulation

(angina, MI, CHF)Kidneys

(nephropathy, ESRD)

Peripheral Nervous

System

(peripheral neuropathy) Peripheral Vascular Tree

(peripheral vascular disease,

gangrene, amputation)

Tissue Damage in Many Organ Systems Leads to Serious Long-Term Complications in T2DM

http://www.eatlas.idf.org/complications Accessed August 15

Russo E, et al. Diabetes Metab Syndr Obes. 2013; 6: 161–170.

ESRD: End- Stage Renal Disease

Luk AO, et al. Diabetes Care. 2014 Jan;37(1):149-57

*Per 100,000

http://www.worldlifeexpectancy.com/cau

se-of-death/kidney-disease/by-country/

accessed 2012 Oct.

http://www.worldlifeexpectancy.com/cause-of-death/kidney-disease/by-country/

GN: Glomerulonephritis

Rashad S. Barsoum. Kidney International Supplements (2013) 3, 164–166

A1 A2 A3

Normal to

mildly

increased

Moderately

increased

Severely

increased

<30 mg/g

<3 mg/mmol

30-300 mg/g

3-30 mg/mmol

>300 mg/g

>30 mg/mmol

• CKD is defined as abnormalities of kidney structure or function, present for >3

months, with implications for health and CKD is classified based on cause, GFR

category, and albuminuria category (CGA).

KDIGO Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int Suppl. 2013;3:136-150.

http://www.kdigo.org/clinical_practice_guidelines/pdf/CKD/KDIGO_2012_CKD_GL.pdf Accessed February 26, 2013

G1 Normal or high ≥90

G2 Mildly decreased 60-89

G3aMildly to moderately

decreased45-59

G3bModerately to

severely decreased30-44

G4 Severely decreased 15-29

G5 Kidney failure <15

GF

R c

ate

go

ries (

ml/

min

/

1.7

3 m

²)

Desc

rip

tio

n a

nd

ran

ge

Persistent albuminuria categories

Description and range

Green: low risk (if no other markers of kidney disease, no CKD); Yellow: moderately increased risk; Orange: high risk; Red, very high risk.

Prognosis of CKD by GFR

and Albuminuria Categories:

KDIGO 2012

Category

Spot collection

(µg/mg creatinine)

Normal <30

Increased urinary albumin

excretion* ≥30

ADA. VI. Prevention, Management of Complications. Diabetes Care 2014;37(suppl 1):S44; Table 11

*Historically, ratios between 30 and 299 have been called microalbuminuria and

those 300 or greater have been called macroalbuminuria (or clinical

albuminuria).

Decreasing HbA1c Is a Real Challenge

With Renal Impairment Patients

Treat to target increases the risk of hypoglycemia in ACCORD, VADT and ADVANCE

1. ACCORD Study Group. N Engl J Med. 2008;358:2545–2559 2. Duckworth W, et al. N Engl J Med. 2009;360:129–1393. ADVANCE Collaborative Group. N Engl J Med. 2008;358:2560–2572

ACCORD1 VADT2 ADVANCE3

P <0.001

Even

ts (

%)

Standard Intensive

16

6

4

2

0

14

12

10

8

18

P <0.01

Standard Intensive

Even

ts p

er

10

0 p

ati

en

t-years

6

4

2

0

14

12

10

8

P <0.001

Standard Intensive

Even

ts p

er

10

0 p

ati

en

ts p

er

ye

ar

0.6

0.4

0.2

0

0.8

0.7

0.5

0.3

0.1

Hypoglycemia and Renal Impairment

• Longstanding type 2 diabetes in patients with advanced

kidney disease often requires insulin therapy.

• Insulin dosage is a real challenge in a renal impaired

population due to impaired catabolism and clearance of

insulin.

• The renal clearance of insulin shows little change if the

glomerular filtration rate (GFR) is above 40 mL/min, but it

falls precipitously with further progression of chronic kidney

disease, especially when GFR is less than 15–20 mL/min.

Lukashevich V, et al. Vasc Health Risk Manag. 2013;9:21-8.

Management of CKD in Diabetes

NICE Diabetes with Kidney Disease: Key Facts MARCH 2011

NICE Diabetes with Kidney Disease: Key Facts MARCH 2011

SUs=sulfonylureas; T2DM=type 2 diabetes melllitus; *Requiring medical assistance or hospital admission

UK Prospective Diabetes Study Group. Diabetes.1995;44:1249–1258.

Cumulative Incidence of Hypoglycemia in T2DM over 6 Years in UKPDS

45

3.3

76

11.2

0

10

20

30

40

50

60

70

80

Sulfonylurea (n=922)

Insulin (n=689)

Sulfonylurea Insulin Sulfonylurea Insulin

Pati

en

ts (

%)

Any hypoglycema Major hypoglycemia*

HbA1c = 7.1% in all groups

70% increased risk

40% increased risk


http://www.medscape.org/viewarticle/437273

http://www.elmhurst.edu/~chm/vchembook/604glycogenesis.html

National Kidney Foundation. KDOQI Clinical Practice Guideline for Diabetes

and CKD: 2012 update. Am J Kidney Dis. 2012;60(5):850-886.

~7.0%

to prevent or delay

progression of the

microvascular

complications of

diabetes, including

DKD

Not

<7.0%

in patients at risk

of hypoglycemia.

>7.0%

In individuals with

co-morbidities or

limited life

expectancy and risk

of hypoglycemia

Adapted from: Jindal A, et al. Endocrinol Metab Clin North Am. 2013 Dec;42(4):789-808

Diabetes indices and progresses

RI

RI increased risk of

hypoglycemia

Limited therapeutic

options Less control

Worsen of RI

CKD: Chronic Kidney Disease.

Jindal A, et al. Endocrinol Metab Clin North Am. 2013 Dec;42(4):789-808

Better glycemic and blood pressure control

Older oral hypoglycemic agents is either contraindicated or requires dosage adjustment in CKD

New medications for diabetes have been approved recently and many can be used safely in patients with CKD

Vildagliptin

Does it have evidence in diabetic renal

impaired patients !?!

Vildagliptin Use With Renal Impairment Patient

• Referring to EMA Recommendations and Locally

Approved Basic Prescribing Information:

EMA = European medical agency

Galvus Locally approved Basic Prescribing Information 2012

To assess long-term safety and efficacy of vildagliptin (50 mg qd) in

patients with T2DM and moderate or severe renal impairment (RI)

*Randomized: patients must remain on their current anti-diabetic therapy (stable dose for at least 4 weeks prior to visit 1) or remain untreated for the

duration of the study if patient is not on anti-diabetic therapy at study entry (unless patient meets criteria for rescue medication).

Total of 525 includes 10 patients with mild RI revealed during reclassification by MDRD method: 7 were randomized to vildagliptin, 3 to placebo, but

data from mild RI patients are not reported

1) Primary objective = safety and tolerability

2) Secondary objective = efficacy

(N=289) Vildagliptin 50 mg qd +

Placebo run-in plus

stable dose of current

therapy*

(N=226) Placebo +

24 weeks2 weeks

N=525

Adapted from Lukashevich V et al. Diabetes Obes Metab. 2011; 13:947-954

Adapted from W. Kothny,et al. Diabetes Obes Metab. May 2012

28 weeks double-blind treatment

current therapy (N=216)

current therapy (N=153)

-0.6

-0.2

-0.4

Moderate RI*

Vildagliptin 50mg QD

Placebo

Between-group Differance

-0.8

-0.1

-0.7

Severe RI*

Vildagliptin 50mg QD

Placebo

Between-group Differance

Duration :1 year

(p<0.0001)(p=0.005)

The overall safety and tolerability of vildagliptin 50 mg qd in patients with moderate

or severe RI was comparable with that of placebo.


RI: renal impairment

*Baseline in moderate and severe RI patient was 7.8% and 7.7% respectively

BL HbA1c BL HbA1c

-0.4

-0.7

Vildagliptin or Placebo Between-group difference

Moderate RI Severe RI

Hb

A1c A

dju

ste

d m

ea

n c

han

ge

(%)

fro

m b

ase

line

Duration :1 year

RI: renal impairment

Baseline in moderate and severe RI patient was 7.8% and 7.7% respectively

(p=0.005)

(p<0.0001)


(baseline=7.8%) (baseline=7.6%)

Moderate RI [n (%)] Severe RI [n (%)]

Event category

Vildagliptin 50

mg qd

(N=122)

Placebo

(N=89)

Vildagliptin

50 mg qd

(N=94)

Placebo

(N=64)

Any adverse event 103 (84.4) 76 (85.4) 80 (85.1) 56 (87.5)

Any serious adverse event 26 (21.3) 17 (19.1) 23 (24.5) 16 (25.0)

Any adverse event leading

to discontinuation6 (4.9) 5 (5.6) 9 (9.6) 4 (6.3)

RI, renal impairmentAdapted from W. Kothny,et al. Diabetes Obes Metab. May 2012

The percentage of patients achieving endpoint HbA1c <7.0% in the vildagliptin group (33/73

patients, 45.2%) was twice that in the placebo group (13/57 patients, 22.8%, P = 0.008).


45.20%

22.80%

0%

5%

10%

15%

20%

25%

30%

35%

40%

45%

50%

Insulin+ Vilda 50mg qd n=33/73 Insulin+ placebo n=13/57

Patients achieving endpoint HbA1c <7.0%

P = 0.008

post hoc sub-analysis of 24-week study

• A higher % of patients reported ≥ 2 events (72.7% with placebo versus 47.4% with vildagliptin).

• Severe hypoglycemia was reported at a similarly low rate in the two groups (2.0% with

vildagliptin and 2.6% with placebo).

47.40%

72.70%

0%

10%

20%

30%

40%

50%

60%

70%

80%

Insulin+ Vilda 50mg Insulin+ placebo

% of patients reported ≥ 2 events

2.00%

2.60%

0%

1%

1%

2%

2%

3%

3%

Insulin+ Vilda 50mg Insulin+ placebo

% of patients with severe hypoglycemia

Lukashevich V, et al. Vasc Health Risk Manag. 2013;9:21-8. post hoc subanalysis of 24-week study

Vildaglitpin in managing T2D with renal impairment ...

Is goodoption for RI

patients

Provides effective glycemic control

Has low risk of

hypoglycimia

Agenda




Optimizing the Management of T2D Patients....

Adapted from http://www.indexmundi.com/egypt/demographics_profile.html , https://www.cia.gov/library/publications/the-world-factbook/geos/eg.html , http://en.worldstat.info/World

accessed 22-2-2014

http://www.indexmundi.com/egypt/demographics_profile.html

https://www.cia.gov/library/publications/the-world-factbook/geos/eg.html

http://en.worldstat.info/World

2013

≥60 Years

≤60 Years

International Diabetes Federation. Managing Older People with Type 2 Diabetes Global Guidelines.

http://www.idf.org/sites/default/files/IDF%20Guideline%20for%20Older%20People.pdf accessed 15-12-2013

2050

≥60 Years

≤60 Years

These changes present significant challenges to welfare, pension, and

healthcare systems in both developing and developed nations

• Diabetes-related complications are the major

causes of morbidity, disability and mortality in

older patients with type 2 diabetes:

• There is now overwhelming evidence that the

level and duration of glycemia influences the

development of diabetes-related complications

Sinclair 2004. Clinical guidelines for type 2 diabetes mellitus. EDWOP 2004

Microvascular: Neuropathy,Retinopathy,Nephropathy

Macrovascular: Cardiovascular disease, Stroke

Cost in US$ millions

Institutional care Outpatient careOutpatient medicines

and supplies

<45 years 45-64 years ≥65 years

American Diabetes Association. Diab Care 2008;31:596-615

• Advanced age

• Recent hospitalization

• Intercurrent illness

• Chronic liver, renal or

cardiovascular disease

• Endocrine deficiency

(thyroid, adrenal, pituitary)

• Loss of normal counter-

regulation

• Hypoglycaemic

unawareness

SU=sulfonylurea.

Adapted from Chelliah A, Burge MR. Drugs Aging. 2004; 21: 511–530.

I. Patient risk factors

• Poor nutrition or fasting

• Prolonged physical

exercise

• Alcohol (ethanol)

• Use of SU and / or insulin

• Drug interactions with SUs

III. Drug risk factors

II. Lifestyle risk factors

T2DM=type 2 diabetes mellitus.

Greco D, et al. Exp Clin Endocrinol Diabetes. 2010; 118: 215–219.

Decompensated

diabetes39%

Intercurrent

illness14%

Acute

cardiovascular events

13%

Chronic

complications of diabetes

17%

Severe

hypoglycaemia17%

Molecule with Smart Mechanism of Action

1Galvus Summary of Product Characteristics, Feb 2011, Section 4.5.

Vildagliptin is not metabolised by the

cytochrome P450 pathway1

Studies in healthy volunteers showed vildagliptin had no

clinically relevant pharmacokinetic interactions with

digoxin (Pgp substrate), warfarin (CYP2C9 substrate),

amlodipine, ramipril, valsartan or simvastatin1

Pooled safety and efficacy analysis of all randomised, double-blind

studies that:

• Dosed vildagliptin 50 mg twice daily

• Included patients ≥75 years

• Duration ≥24 weeks

• 10 studies were included, total n=12,326

No. patients receiving vildagliptin

<75 years ≥75 years

Safety

population

5984 132

Monotherapy Add-on therapy Monotherapy Add-on therapy

Efficacy

population2303 910 62 25

Vildagliptin is approved for 50 mg once or twice daily in combination with metformin or a TZD,

and vildagliptin 50 mg once daily in combination with a sulfonylurea.

Schweizer A, et al. Diabetes Obes Metab. 2011; 13: 55–64.

-1.1-1.2

-1.0

-0.8

-0.6

-0.4

-0.2

0.0

Ch

an

ge in

Hb

A1

c (

%)

fro

m b

ase

lin

e

n=

BL (%)=

25

8.5

*

Pooled analysis (24 weeks) of 3 add-on therapy studies, patients ≥75 years

HbA1c1

-0.2

-0.5

-0.4

-0.3

-0.2

-0.1

0.0

n=

BL (kg)=

Ch

an

ge in

weig

ht

(kg

)

fro

m b

ase

lin

e

25

82.8

Body weight1

n 31

Any events, n

(%)0 (0.0%)

Severe

events, n (%)0 (0.0%)

Hypoglycaemia2

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 <75 years.1Efficacy pool: all randomised, double-blind, controlled, parallel-group studies with duration ≥24 weeks and with patients ≥75 years. Only includes studies

with the approved dose of 50 mg twice daily. 2Safety pool: a pool of 38 Phase II and III studies (monotherapy and add-on therapy).

*P <0.05 vs baseline (within group). AEs=adverse events; bid=twice daily; BL=baseline; HbA1c=haemoglobin A1c; SAEs=serious adverse events.


Vilda 50 mg bid

n=5984

Comparators

n=6041Vilda 50 mg bid

n=132

Comparators

n=169

Any AEs

n (%)147.9

4139 (69.2)

177.3

4174 (69.1)

133.9

86 (65.2)

200.6

114 (67.5)

Drug-related AEs

n (%)14.9

943 (15.8)

26.0

1325 (21.9)

14.5

18 (13.6)

21.8

24 (14.2)

SAEs

n (%)7.8

533 (8.9)

8.9

538 (8.9)

8.8

12 (9.1)

16.5

19 (11.2)

Discontinuation due to

AEs

n (%)

4.7

337 (5.6)

6.1

391 (6.5)

7.2

10 (7.6)

7.5

9 (5.3)

Deaths

n (%)0.3

24 (0.4)

0.3

21 (0.3)

0.0

0 (0.0)

1.7

2 (1.2)

AEs=adverse events; bid=twice daily; SAEs=serious adverse events; SYE-adj=subject year exposure-adjusted; vilda=vildagliptin.

Safety pool: a pool of 38 Phase II and III studies. Comparators group includes active comparator or placebo.


Age <75 years Age ≥75 years

In this sub-analysis of data derived from a previously

described randomized, double blind, parallel-group, 24-week

study, 105 patients (50 randomized to vildagliptin 50 mg qd

and 55 to placebo) ≥ 75 years (mean age~78 years) with

T2DM and moderate or severe RI (mean baseline estimated

glomerular filtration rate~35 ml/min/ 1.73 m2) were included.

Schweizer, et al. Diabetes Ther. Experience with Vildagliptin in Patients ≥75 Years with Type 2 Diabetes and Moderate or Severe Renal Impairment.

2013 Dec;4(2):257-67.

(A) p<0.001 (between-group difference).

(B) p = 0.970 (between-group difference).

BL= baseline

Schweizer, et al. Diabetes Ther. Experience with Vildagliptin in Patients ≥75 Years with Type 2 Diabetes and Moderate or Severe Renal Impairment.

2013 Dec;4(2):257-67.

Vildagliptin in the elderly: summary

HbA1c=haemoglobin A1c; SUs=sulfonylureas; T2DM=type 2 diabetes mellitus. 1Adapted from Cowie CC, et al. Diabetes Care. 2009; 32: 287–294; 2Araki A, Ito H. Geriatr Gerontol Int. 2009; 9: 105–114; 3Schweizer A, et al. Diabetes Obes Metab. 2011; 13: 55–64.

VILDAGLIPTIN

Agenda




Vildagliptin safety is well assessed in different meta analysis

Safety of Vildagliptin is Well Established

• In meta – analysis of 38 clinical trials include more than 14.000 patients vildagliptin shows no increased risk of:

•Pancreatitis-related AEs

•ALT / AST or Bilirubin elevation

•Renal AEs and SAEs in patients with normal renal function and mild renal impairment patients

• Infection and skin related adverse events

vs. comparators (placebo, insulin and other OAD)

Ligueros-Saylan et al. DIABETES, OBESITY AND METABOLISM Volume 12 No. 6 June 2010

• About 40% of patients had ≥ 2 documented CV risk factors in

addition to T2DM:

– dyslipidaemia

– hypertension

– age ≥65 years

• Over 15% had a high CV risk status:

– defined as a previous history of CCV events in the

Standard MedDRA Queries of ‘ischaemic heart disease,

cardiac failure, ischaemic cerebrovascular conditions

and/or embolic, thrombotic events.


Patient Characteristics

Vildagliptin: In more than 14,000 patients No Increased Risk for Adjudicated CV Events,

Relative to All Comparators

AEs=adverse events; bid=twice daily; CI=confidence interval; CV=cardiovascular; M-H RR=Mantel-Haenszel risk ratio; qd=once daily; vilda=vildagliptin. #Vs comparators (all non-vildagliptin treatment groups). All-study safety population.

‡Guidance for Industry: Diabetes Mellitus - Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes, U.S. Department

of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER), December 2008.

Schweizer A, et al. DOM 2010 in press.

Vildagliptin Reference M-H RR

n / N (%) n / N (%) (95% CI)

Vilda 50 mg qd# 10 / 1393 (0.72) 14 / 1555 (0.90) 0.88 (0.37–2.11)

Vilda 50 mg bid# 81 / 6116 (1.32) 80 / 4872 (1.64) 0.84 (0.62–1.14)

Risk Ratio

Incidences and Odds Ratios for

Adjudicated CV Events by Treatment

Vildagliptin better Vildagliptin worse

0.1 1 10

#Meta-analysis of vildagliptin 50 mg bid data vs all comparators according to the methodology set

by the US Food and Drug Administration‡ [50 mg bid odds ratio = 0.84 (95% CI 0.62–1.14)].

• 9,599 patients were treated with GALVUS® (50 mg once or twice

daily), as either monotherapy or in combination with another

OAD or insulin

• >40% had 2 or more CV risk factors (hypertension,

dyslipidaemia or age ≥60 years for females or 55 years for

males)

• Nearly a fifth (18%) had high CV risk status*

• 27% of patients ≥65 years

• 38% of patients had longstanding T2DM (>5 yrs)

• Almost half (49%) obese (BMI ≥30 kg/m2)

• 41.3% had renal impairment

Mclnnes Meta Analysis - 2014

• A recent meta-analysis has extended the assessment of GALVUS® CV safety to

• 40 Phase III and Phase IV studies (N=17,446), including trials in high-risk patients,

such as those with heart failure or moderate/several renal impairment [McInnes 2014]

• Primary End Point :

– Occurrence of MACE (myocardial infarction,

stroke and CV death).

• Secondary End Point :

– Assessments of the individual MACE

components and HF events (requiring

hospitalization or new onset) .

McInnes G, et al. Diabetologia. 2014;57(Suppl. 1):Abstract (presentation number 891)

CV safety of vildagliptin: an adjudicated meta-analysis of 40 studies

Incidences and risk ratios for adjudicated MACE and its individual components*

Vildagliptin

n/N (%)

Comparators

n/N (%)

M-H RR

(95% CI)

MACE composite

endpoint83/9599 (0.86) 85/7102 (1.20) 0.82 (0.61–1.11)

Myocardial

infarction38/9599 (0.40) 35/7102 (0.49) 0.87 (0.56–1.38)

Stroke 24/9599 (0.25) 25/7102 (0.35) 0.84 (0.47–1.50)

CV death 25/9599 (0.26) 28/7102 (0.39) 0.77 (0.45–1.31)

• This updated, large meta-analysis continues to indicate that vildagliptin is not

associated with an increased risk for adjudicated MACE relative to comparators.

• It now includes more patients with advanced renal impairment or CV disease

history including heart failure

Vildagliptin better Comparator better

0.01 0.10 1.0 10.0 100.0

Incidences and risk ratios for adjudicated MACE* in various subgroups

Vildagliptin

n/N (%)Comparators

n/N (%)

M-H RR

(95% CI)

0.74 (0.52–1.05)64/3928 (1.63)57/5310 (1.07)Male

0. 1 1.0 10.0 100.00.01Vildagliptin better Comparator better

i) MACE in subgroups by age, gender and CV risk status

Gender

1.06 (0.61–1.85)21/3174 (0.66)26/4289 (0.61)Female

0.63 (0.42–0.95)50/5119 (0.98)39/7239 (0.54)<65 years

1.09 (0.70–1.71)35/1983 (1.77)44/2360 (1.86)≥65 years

1.01 (0.51–2.00)16/3609 (0.44)19/5167 (0.37)No

0.78 (0.56–1.09)69/3493 (1.98)64/4432 (1.44)Yes

0.93 (0.66–1.30)62/3836 (1.62)66/4391 (1.50)Studies ≥52 weeks

Age (years)

High CV risk status**

ii) MACE in subgroup of long-term studies

*MACE, major adverse cardiovascular (CV) events–non-fatal myocardial infarction, non-fatal stroke or CV death; **High CV risk status ‘yes’

includes patients with a previous history of CV events in the standard MeDRA Queries of ‘ischemic heart disease, cardiac failure, ischemic

cerebrovascular conditions and /or embolic thrombotic events, arterial’. Vildagliptin = 50 mg qd/bid; M-H RR, Mantel-Haenszel risk ratio.

Adapted from McInnes G et al. Poster no 891 presented at the 50th EASD Annual Meeting, Sep 15–19, 2014, Vienna, Austria.

Vildagliptin

n/N (%)

Comparators

n/N (%)

M-H RR

(95% CI)

Vildagliptin

50 mg od/bid41/9599 (0.43) 32/7102 (0.45) 1.08 (0.68–1.70)

Vildagliptin

50 mg od20/2201 (0.91) 19/2451 (0.78) 1.19 (0.63–2.26)

Vildagliptin

50 mg bid21/7398 (0.28) 24/6229 (0.39) 0.99 (0.55–1.77)

Vildagliptin was not associated with increased risk of HF: Pooled safety data from ~17,000 T2DM patients

• Incidences and risk ratios for adjudicated heart failure events*

In patients with T2DM†, incidences of adjudicated heart failure events (New onset HF

or HF hospitalization) were similar in the vildagliptin and comparator treatment

groups

Vildagliptin better Comparator better

0.01 0.10 1.0 10.0 100.0

M-H RR=Mantel-Haenszel risk ratio

Evans M, et al. Poster presented at 50th EASD Annual Meeting, Vienna, Austria, 15–19 September 2014;

Evans M, et al. Diabetologia. 2014;57(Suppl. 1):Abstract (presentation number 888)

Vildagliptin Safety: summary

VILDAGLIPTIN

ueda2016 symposium - managing special population in diabetic patient,vildagliptin evidence - ayman...

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