ueda2013 t2-dm achieving target challenges_d.lobna

T2DM Achieving target challenges

Patient centered approach

By:Lobna Farag Eltoony

Head of diabetes and Endocrinology Unit

Department Of Internal Medicine

Assuit University

Topics for discussion

T2DM worldwide burden

Individualize patient approach

DPP4 I & practical facts

Insulin in T2DM

Beyond glucose control

ME & Diabetes prevalence

“increasingly complex and to some extent controversial”

nature of glycemic management for type 2 diabetes, the

“widening array of pharmacological agents now available,

mounting concerns about their potential adverse effects and

new uncertainties regarding the benefits of intensive

glycemic control on macrovascular complications,”

ADA-EASD Position Statement: Management of

Hyperglycemia in T2DM

3. ANTI-HYPERGLYCEMIC THERAPY

•Glycemic targets

- HbA1c < 7.0% (mean PG 150-160 mg/dl [8.3-8.9 mmol/l])

- Pre-prandial PG <130 mg/dl (7.2 mmol/l)

- Post-prandial PG <180 mg/dl (10.0 mmol/l)

- Individualization is key:

Tighter targets (6.0 - 6.5%) - younger, healthier

Looser targets (7.5 - 8.0%+) - older, comorbidities, hypoglycemia prone, etc.

- Avoidance of hypoglycemia

PG = plasma glucose Diabetes Care, Diabetologia. 19 April 2012 [Epub ahead of print]

Figure 1 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)

T2DM Anti-hyperglycemic Therapy: General Recommendations Diabetes Care, Diabetologia. 19 April 2012

]

Adapted Recommendations: When Goal is to Avoid Weight Gain Diabetes Care, Diabetologia. 19 April

2012 [Epub ahead of print]

Adapted Recommendations: When Goal is to Avoid Hypoglycemia Diabetes Care, Diabetologia. 19 April 2012

[Epub ahead of print]

Adapted Recommendations: When Goal is to Minimize Costs Diabetes Care, Diabetologia. 19 April 2012

[Epub ahead of print]

Sitagliptin Enhances Active Incretin Levels

Through Inhibition of DPP-41–4

By increasing and prolonging active incretin levels, sitagliptin increases insulin release

and decreases glucagon levels in the circulation in a glucose-dependent manner.

Release of

active incretins

GLP-1 and GIPa

Blood glucose in

fasting and

postprandial states

Ingestion

of food

Glucagon

from alpha cells

(GLP-1)

Hepatic

glucose

production

GI tract

DPP-4

enzyme

Inactive

GLP-1

X Sitagliptin

(DPP-4

inhibitor)

Insulin from

beta cells

(GLP-1 and GIP)

Glucose-dependent

Glucose-dependent

Pancreas

Inactive

GIP

Beta cells

Alpha cells

Peripheral

glucose

uptake

DPP-4=dipeptidyl peptidase 4; GI=gastrointestinal; GIP=glucose-dependent insulinotropic peptide; GLP-1=glucagon-like peptide-1. aIncretin hormones GLP-1 and GIP are released by the intestine throughout the day, and their levels increase in response to a meal. 1. Kieffer TJ et al. Endocr Rev. 1999;20(6):876–913. 2. Ahrén B. Curr Diab Rep. 2003;3(5):365–372. 3. Drucker DJ. Diabetes Care. 2003;26(10):2929–2940, 4. Holst JJ. Diabetes Metab Res Rev. 2002;18(6):430–441.

N

N

N

N

N

N

N

O

O

NH2

Linagliptin

Vildagliptin

N

O

N

N H

O H

N

N N

N

N

O

O

Alogliptin

Sitagliptin

F

F F O

F F

F

NH2

N

N N

N

DPP-4 Inhibitors Differ Chemically

Saxagliptin

N

O

OH

NH2

Rationale for Once-Daily Dosing of

Sitagliptin Based on DPP-4 Inhibition1,a

14 DPP-4=dipeptidyl peptidase-4; qd=once daily. a97% weighted average inhibition of plasma DPP-4 activity through 24 hours postdose. bDPP-4 inhibition corrected for sample assay dilution.

1. Alba M et al. Curr Med Res Opin. 2009;25(10):2507–2514.

Single-dose study in healthy subjects (n=6)

Hours Postdose 0 1 2 4 6 8 12 16 24

DP

P-4

Inhi

bitio

n, %

b

0

20

40

60

80

100

Sitagliptin 100 mg qd

Sitagliptin is a different molecule

Sitagliptin Vildagliptin

Molecular structure

Half Life (T1/2) 12.4 hrs 2-3 hrs

DPP-4 Inhibition* post 24 hrs 100mg QD 80-97% @ 24hrs 50 mg QD: 20% @ 24 hrs

50 mg BID: >80% @ 12hrs

DPP-4 Peak Inhibition ~97% ~95%

Selectivity for DPP-IV vs. DPP-8/DPP-9* 2600 fold for DPP4 vs. DPP-8

10,000 fold for DPP4 vs. DPP-9

270 fold for DPP4 vs. DPP-8

32 fold for DPP4 vs. DPP-9

Metabolism ~16% metabolized

69% metabolized

mainly renal

(inactive metabolite)

Bioavailability ~87% 85%

Liver Monitoring NO YES

Elimination Kidney (87%)

79% mostly unchanged

Kidney (85%)

23% unchanged

Liver (15%)

FDA YES NO

* All use different proprietary assays with different dilutions and therefore % DPP-4 inhibition cannot be compared across assays

H O

N H

O

N

N C

F

F

F O N

N H 2

N N N

C F 3

Data on file, MSD

Week 30

Addition of Sitagliptin or Glimepiride in Patients

Inadequately Controlled on Metformin:

Study Design1

Continue stable dose of metformin

Single-blind Placebo Run-in

Double-blind Treatment Period

Week –2 Day 1

Patients ≥18 years of age with T2DM on stable dose of metformin (≥1500 mg/day) for ≥12 weeks and HbA1c 6.5%– 9.0%

Glimepiride (started at 1 mg qd and up-titrated until week

18 as needed up to maximum dose of 6 mg qd)

qd=once daily; R=randomization; T2DM=type 2 diabetes mellitus.

1. Arechavaleta R et al. Diabetes Obes Metab. 2011;13(2):160–168.


Week –4

R

Screening Period

HbA1c-Lowering Efficacy of Sitagliptin at

Week 30 Was Noninferior to That of Glimepiride in Patients

Inadequately Controlled on Metformin1

LS=least squares; SE=standard error.

aMean dose of glimepiride (following the 18-week titration period) was 2.1 mg per day.


Week

LS

Mean

(±

SE

) H

bA

1c,

%

Per-Protocol Population

6.0

6.2

6.4

6.6

6.8

7.0

7.2

7.4

7.6

7.8

8.0

0 6 12 18 24 30

(95% CI)

0.07% (–0.03, 0.16)

Sitagliptin 100 mg + metformin (n=443)

Glimepiridea + metformin (n=436)

–0.47

–0.54


Inadequately Controlled on Metformin: Clinical

Assessment of Hypoglycemia Over 30 Weeks1

APaT Population

APaT=all patients as treated; CI=confidence interval.

aMean dose of glimepiride (following the 18-week titration period) was 2.1 mg per day.


7

22

0

5

10

15

20

25

Patients

With ≥

1

Hypogly

cem

ic E

pis

ode,

%

(95% CI)

–15.0% (–19.3, –10.9)

(P<0.001)

Sitagliptin 100 mg + metformin (n=516)

Glimepiridea + metformin (n=518)


Inadequately Controlled on Metformin:

Body Weight Change from Baseline1

LS

Mean C

hange (±

SE

) in

Body

Weig

ht

Fro

m B

aselin

e,

kg

Week

0 6 12 18 24 30

–1

0

1

2

APaT Population

Sitagliptin 100 mg + metformin

Glimepiridea + metformin

= –2.0 kg

(P<0.001)

–0.8 kgb

1.2 kgb

APaT=all patients as treated; LS=least squares; SE=standard error.

aMean dose of glimepiride (following the 18-week titration period) was 2.1 mg per day. bLS mean body weight change at 30 weeks.


Earlier and Appropriate Intervention May

Improve Patients’ Chances of Reaching Goal

OAD=oral antidiabetic agent. Adapted from Del Prato S et al. Int J Clin Pract. 2005;59(11):1345–1355. Copyright © 2005. Adapted with permission of Blackwell Publishing Ltd.

Published Conceptual Approach

Hb

A1c

Go

al

Mean HbA1c

of patients Duration of Diabetes

OAD

monotherapy

Diet and

exercise

OAD

combination

OAD

up-titration

OAD +

multiple daily

insulin

injections

OAD +

basal insulin

Conventional stepwise treatment approach

Earlier and more aggressive intervention approach

6

7

8

9

10

Initial Combination Therapy With Sitagliptin Plus Metformin

vs Metformin Monotherapy: HbA1c Results by

Mean Baseline HbA1c at Week 18

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

Data on file, MSD.

Hb

A1c

LS

Mea

n C

han

ge

fro

m

Bas

elin

e, %

Baseline HbA1c,% <8 ≥8 and <9 ≥9 and <10 ≥10 and <11 ≥11 FAS (Week 18)

P=0.009

P<0.001

P<0.001

Mean HbA1c,% 7.6 8.4 9.5 9.4 10.4 12.2

n=

–1.1

–1.6

–2.0

–2.9

–3.6

–2.7

–2.1

–1.7

–1.1

–0.8

–4.0

–3.5

–3.0

–2.5

–2.0

–1.5

–1.0

–0.5

0

Sitagliptin/metformin FDC 50/1000 mg bid

Metformin 1000 mg bid

99 95 99 111 87 101 124 109 150 148

P=0.158

P=0.111

ADA-EASD Position Statement: Management of

Hyperglycemia in T2DM

Long (Detemir)

Rapid (Lispro, Aspart, Glulisine)

Hours

Long (Glargine)

0 2 4 6 8 10 12 14 16 18 20 22 24

Short (Regular)

Hours after injection

Insu

lin le

vel

•Therapeutic options: Insulin

Intermediate (NPH)

Effect of Sitagliptin in

Patients With Type 2 Diabetes and Inadequate

Glycemic Control on Insulin Therapy (Alone or in

Combination With Metformin)

Diabetes, Obesity and Metabolism 2010

Addition of Sitagliptin to Insulin Therapy: Study Design

Single-blind placebo run-in

period

• Continue on a stable dose of insulin with or without metformin

• Begin single-blind run-in period

Randomization Week 24

24-Week Stable Insulin Dose Period

QD=daily.

Diabetes, Obesity and Metabolism 12: 167–177, 2010.

• Patients with type 2 diabetes

• Age >21 years

• Receiving insulin (including glargine, detemir, ultralente, NPH, lente, or premixed insulin) alone or with metformin ≥1500 mg/day

• Not receiving premeal short-acting insulin

• HbA1c ≥7.5% and ≤11%

Placebo (n=319)

Sitagliptin 100 mg QD (n=322)

R

Screening

visit Week –2

0 6 12 18 24

0.1

Addition of Sitagliptin to Insulin Therapy: HbA1c Change 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.


FAS Population (LOCF)

Placeboa

Sitagliptina

Difference = –0.56%

(P<0.001)

Hb

A1

c L

S M

ean

Ch

an

ge

Fro

m B

aselin

e, %

(S

E)

Weeks

0.0

–0.8

–0.7

–0.6

–0.5

–0.4

–0.3

–0.2

–0.1

–0.8

–0.03%

–0.59%

(n=305)

(n=312)

Sitagliptin

Placebo

Addition of Sitagliptin to Insulin Therapy: HbA1c Change

From Baseline by Insulin Type

FAS Population at 24 Weeks (LOCF)a

P-value for treatment by subgroup interaction = 0.949

aExcluding data after initiation of rescue therapy.



Hb

A1

c L

S M

ean

Ch

an

ge

Fro

m B

aselin

e, %

(S

E)

–1.0

0.0

–0.8

–0.6

–0.4

–0.2

Receiving Premixed

Insulin

Receiving Long- or Intermediate-acting

Insulin

–0.58

–0.02

–0.61

–0.04

n=80 n=80

n=225 n=232

P<0.001 P<0.001

Mean baseline HbA1c, % 8.59 8.50 8.76 8.69

Addition of Sitagliptin to Insulin Therapy: HbA1c Change From Baseline by Metformin

Use

Not Receiving Metformin

Receiving Metformin

N=223 N=229

Sitagliptin

Placebo

P-value for treatment by subgroup interaction = 0.437

Hb

A1

c L

S M

ean

Ch

an

ge

Fro

m B

aselin

e, %

(S

E)

–1.0

0.4

–0.8

–0.6

–0.4

–0.2

0.2

0.0

–0.55

0.10

–0.66

–0.13

P<0.001 P<0.001

n=82 n=83 n=223 n=229

FAS Population at 24 Weeks (LOCF)a

aExcluding data after initiation of rescue therapy.



Mean baseline HbA1c, % 8.68 8.76 8.73 8.60

bid=twice daily; qd=daily; R=randomization. Diabetes, Obesity and Metabolism 14: 67–76, 2012.

wk 0

1091 patients with type 2 diabetes

Week 24

Placebo




Sitagliptin 50 mg/

metformin 500 mg bid

Sitagliptin 50 mg/


R

Week 104

Metformin 1,000 mg bid




Sitagliptin 50 mg/


Sitagliptin 50 mg/


24-Week (Phase A) Extension Phase

Patients were instructed to

consume a meal within 15

min & blood samples were

collected at

-35, -10, 0, 10, 20, 30, 60, 90,

120, 180 min.

•double blind

Conclusions

Initial combination of Sitagliptin & Metformin enhanced the responsiveness of pancreatic B cells to glucose in both fasting & post-prandial states.

Initial combination therapy demonstrated greater improvements in B cell function than individual monotherapies.

Improvements in B cell function were maintained over 2 years treatment period.


32

CHD=coronary heart disease.

1. Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the

United States, 2011. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2011.

Most Patients With Diabetes Die of

Cardiovascular Disease1

National Diabetes Fact Sheet 2011: among people ≥65

years of age

– Heart disease was noted on 68% of diabetes-related death

certificates.

– Risk of stroke is 2 to 4 times greater among people with diabetes

compared with those without diabetes.

– Stroke was noted on 16% of diabetes-related death certificates.

Impact of Intensive Therapy for Diabetes: Summary of Major Clinical Trials

Study Microvasc CVD Mortality

UKPDS

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. Lancet 1998;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. N Engl J Med 2009;361:1024)

34

The DPP -4 I in Cardiovascular

Disease

DPP4i compared with placebo or other treatment, were associated with a reduced risk of MACE (MH-OR 0.689[0.528; 0.899], p=0.006),irrespective of

trial duration, type of DDP4i, or comparator.

0,0

1

0,1

0

1,0

0

10

,00

10

0,0

0

Figure 4

Drugs MH-OR (95%, CI) p # Trials MH-OR (95%, CI) p # Trials

Alogliptin 1.240 [0.059;26.016] 0.890 1 0.630 [0.012;33.048] 0.819 2

Saxagliptin 1.440 [0.498; 4.203] 0.505 6 0.655 [0.382; 1.123] 0.124 8

Sitagliptin 1.047 [0.705; 1.555] 0.820 18 0.740 [0.479; 1.147] 0.173 18

Vildaglptin 0.818 [0.434; 1.543] 0.536 9 0.666 [0.428; 1.036] 0.072 12

Trial duration

< 52 weeks 1.252 [0.778; 2.016] 0.355 24 0.626 [0.444; 0.884] 0.008 30

≥ 52 weeks 0.855 [0.557; 1.312] 0.473 10 0.831 [0.523; 1.321] 0.157 10

Comparator

Acarbose 1.505 [0.061; 37.098] 0.803 1 1.000 [0.090; 11.090] 1.000 1

Liraglutide 1.486[0.217; 10.184] 0.687 2 2.376 [0.291; 19.390] 0.419 2

Metformin 0.526[0.147; 1.883] 0.323 3 0.697[0.291; 1.666] 0.417 5

Sulfonylureas 1.118 [0.624; 2.001] 0.708 4 0.718[0.410; 1.100] 0.098 5

Thiazolidinediones 0.832[0.141; 4.914] 0.839 3 0.411[0.070; 2.428] 0.327 3

Placebo 1.009[0.657; 1.550] 0.968 22 0.705[0.500; 0.993] 0.045 26

OVERALL 1.020[0.742; 1.402] 0.904 35 0.689 [0.528; 0.899] 0.006 43

Figure 2

Malignancies Major Cardiovascular Events

0.001 0.1

Mantel Haenzel Odd Ratio, 95% Confidential Intervals

1.0 10 100

0,0

1

0,1

0

1,0

0

10

,00

10

0,0

0

0.001 0.1 1.0 10 100

Figure 4

0,0

1

0,1

0

1,0

0

10

,00

10

0,0

0

Figure 4


Alogliptin 1.240 [0.059;26.016] 0.890 1 0.630 [0.012;33.048] 0.819 2

Saxagliptin 1.440 [0.498; 4.203] 0.505 6 0.655 [0.382; 1.123] 0.124 8

Sitagliptin 1.047 [0.705; 1.555] 0.820 18 0.740 [0.479; 1.147] 0.173 18

Vildaglptin 0.818 [0.434; 1.543] 0.536 9 0.666 [0.428; 1.036] 0.072 12

Trial duration

< 52 weeks 1.252 [0.778; 2.016] 0.355 24 0.626 [0.444; 0.884] 0.008 30

≥ 52 weeks 0.855 [0.557; 1.312] 0.473 10 0.831 [0.523; 1.321] 0.157 10

Comparator

Acarbose 1.505 [0.061; 37.098] 0.803 1 1.000 [0.090; 11.090] 1.000 1

Liraglutide 1.486[0.217; 10.184] 0.687 2 2.376 [0.291; 19.390] 0.419 2

Metformin 0.526[0.147; 1.883] 0.323 3 0.697[0.291; 1.666] 0.417 5

Sulfonylureas 1.118 [0.624; 2.001] 0.708 4 0.718[0.410; 1.100] 0.098 5


Placebo 1.009[0.657; 1.550] 0.968 22 0.705[0.500; 0.993] 0.045 26

OVERALL 1.020[0.742; 1.402] 0.904 35 0.689 [0.528; 0.899] 0.006 43

Figure 2


0.001 0.1


1.0 10 100

0,0

1

0,1

0

1,0

0

10

,00

10

0,0

0

0.001 0.1 1.0 10 100

Figure 4

0,0

1

0,1

0

1,0

0

10

,00

10

0,0

0

Figure 4


Alogliptin 1.240 [0.059;26.016] 0.890 1 0.630 [0.012;33.048] 0.819 2

Saxagliptin 1.440 [0.498; 4.203] 0.505 6 0.655 [0.382; 1.123] 0.124 8

Sitagliptin 1.047 [0.705; 1.555] 0.820 18 0.740 [0.479; 1.147] 0.173 18

Vildaglptin 0.818 [0.434; 1.543] 0.536 9 0.666 [0.428; 1.036] 0.072 12

Trial duration

< 52 weeks 1.252 [0.778; 2.016] 0.355 24 0.626 [0.444; 0.884] 0.008 30

≥ 52 weeks 0.855 [0.557; 1.312] 0.473 10 0.831 [0.523; 1.321] 0.157 10

Comparator

Acarbose 1.505 [0.061; 37.098] 0.803 1 1.000 [0.090; 11.090] 1.000 1

Liraglutide 1.486[0.217; 10.184] 0.687 2 2.376 [0.291; 19.390] 0.419 2

Metformin 0.526[0.147; 1.883] 0.323 3 0.697[0.291; 1.666] 0.417 5

Sulfonylureas 1.118 [0.624; 2.001] 0.708 4 0.718[0.410; 1.100] 0.098 5


Placebo 1.009[0.657; 1.550] 0.968 22 0.705[0.500; 0.993] 0.045 26

OVERALL 1.020[0.742; 1.402] 0.904 35 0.689 [0.528; 0.899] 0.006 43

Figure 2


0.001 0.1


1.0 10 100

0,0

1

0,1

0

1,0

0

10

,00

10

0,0

0

0.001 0.1 1.0 10 100

Figure 4

0,0

1

0,1

0

1,0

0

10

,00

10

0,0

0

Figure 4


Alogliptin 1.240 [0.059;26.016] 0.890 1 0.630 [0.012;33.048] 0.819 2

Saxagliptin 1.440 [0.498; 4.203] 0.505 6 0.655 [0.382; 1.123] 0.124 8

Sitagliptin 1.047 [0.705; 1.555] 0.820 18 0.740 [0.479; 1.147] 0.173 18

Vildaglptin 0.818 [0.434; 1.543] 0.536 9 0.666 [0.428; 1.036] 0.072 12

Trial duration

< 52 weeks 1.252 [0.778; 2.016] 0.355 24 0.626 [0.444; 0.884] 0.008 30

≥ 52 weeks 0.855 [0.557; 1.312] 0.473 10 0.831 [0.523; 1.321] 0.157 10

Comparator

Acarbose 1.505 [0.061; 37.098] 0.803 1 1.000 [0.090; 11.090] 1.000 1

Liraglutide 1.486[0.217; 10.184] 0.687 2 2.376 [0.291; 19.390] 0.419 2

Metformin 0.526[0.147; 1.883] 0.323 3 0.697[0.291; 1.666] 0.417 5

Sulfonylureas 1.118 [0.624; 2.001] 0.708 4 0.718[0.410; 1.100] 0.098 5


Placebo 1.009[0.657; 1.550] 0.968 22 0.705[0.500; 0.993] 0.045 26

OVERALL 1.020[0.742; 1.402] 0.904 35 0.689 [0.528; 0.899] 0.006 43

Figure 2


0.001 0.1


1.0 10 1000

,01

0,1

0

1,0

0

10

,00

10

0,0

0

0.001 0.1 1.0 10 100

Figure 4

Sitagliptin

N=3415

n (%)

Nonexposed

N=2724

n (%)

Between-Groups

Difference,

% (95% CI)a

Serious clinical adverse experiences ≥0.2% in any group

Coronary artery disease 5 (0.1) 7 (0.3) –0.1 (–0.4, 0.1)

Myocardial infarction 4 (0.1) 5 (0.2) –0.1 (–0.3, 0.1)

Noncardiac chest pain 4 (0.1) 9 (0.3) –0.2 (–0.5, 0.0)

Cholelithiasis 6 (0.2) 2 (0.1) 0.1 (–0.1, 0.3)

Pneumonia 4 (0.1) 5 (0.2) –0.1 (–0.3, 0.1)

aPositive differences indicate that the proportion for the sitagliptin group is higher than the

proportion for the nonexposed group.

“0.0” represents rounding for values that are slightly greater than zero.

Williams-Herman D et al. BMC Endocr Disord. 2008;8:14. Copyright BioMed Central.

Incidences of Serious Adverse Events Were Generally Similar Between Treatment Groups With or Without

Sitagliptin

Sitagliptin pooled safety and tolerability analysis

TECOS is a double-blind randomized, placebo controlled, multi-national trial in patients with Type 2 Diabetes coordinated by the Duke Clinical Research Institute (DCRI) and the University of Oxford Diabetes Trial Unit (DTU).

It is being conducted in around 40 countries, across Australasia, Asia, Europe, North America, South America, India and South Africa, and commenced in 2008.

TECOS aims to compare the impact of adding sitagliptin as part of usual care versus usual care without sitagliptin on cardiovascular outcomes. 14,000 patients will be followed for a minimum of 3 years with the results expected in 2015.

http://www.dcri.duke.edu/

http://www.dtu.ox.ac.uk/

Key Points …. Diabetes is rapidly growing worldwide especially in Egypt

Glycemic targets and glucose-lowering therapies must be individualized.

DPP4I Sitagliptin have a major role in glycemic control without hypoglycemia and with no increase in body weight.

Combination therapy with a DPP-4 inhibitor and metformin offers opportunity for improved glycemic efficacy, complementary mechanisms of action, and a low risk of hypoglycemia without weight gain

Sitagliptin is approved to be add on insulin

Based on studies they can preserve or enhance B cell function

Ability to use in cardiovascular disease markedly increases therapeutic options for our patients

THANK YOU

Health & Medicine

ueda2013 t2-dm achieving target challenges_d.lobna