:

3o 2013

. .

&

..

,
ADA EASD Position statement 2012

()

2 85-95%

2025
> 530

400

2012
371

350
300
250

2000
150

200
150
100

1985
30

50
0
1985

1990

1995

2000

2005

2010

2015

2020

2025

http://www.idf.org/home/index.cfm?node=264

52

12%

24%

40% -2
65%

/
,

MI/

HCG 2011

&


213 (Fu= 14 )

Diabetologia 2012;55:294-302

: 11000 $

: 2600 $

Rubins et al. J Clin End Met 1998;

,
ADA EASD Position statement 2012

DCCT

Kumamoto

UKPDS

9 7.2%

9 7%

8 7%

Retinopathy

63%

69%

17-21%

Nephropathy

54%

70%

24-33%

Neuropathy

60%

Improved

Cardiovascular
disease

41%

16%*

HbA1C

*p=0.052

DCCT/EDIC study: 11-year follow up (total 17 years), showed 57%

reduction in CVD risk.
UKPDS: 10 year follow up (total 20 years), showed significant
reduction in CVD risk
DCCT Research Group. N Engl J Med 1993;329:977
UKPDS 33: Lancet 1998; 352, 837-853
DCCT-EDIC study:NEJM 2006;353:2643
Holman etal:NEJM2008;359




ACCORD

ADVANCE

VADT

62

66

60,4

10

11,5

CVD

77%

40%

90%

3,5

~5

NEJM 2008;358:2537-39

NEJM 2008;358:2630-33

ACCORD STUDY:

The Action to Control Cardiovascular Risk in Diabetes Study Group, N Engl J Med 2008;358:2545-59.

The vicious circle of the

Metabolic Memory

The message is that while

Glucose control is important,
early glucose control way be
critical
EASD 2008

Pr. E. Gale
Editor Diabetologia

DCCT

Kumamoto

UKPDS

9 7.2%

9 7%

8 7%

Retinopathy

63%

69%

17-21%

Nephropathy

54%

70%

24-33%

Neuropathy

60%

Improved

Cardiovascular
disease

41%

16%*

HbA1C

*p=0.052

DCCT Research Group. N Engl J Med 1993;329:977

UKPDS 33: Lancet 1998; 352, 837-853
DCCT-EDIC study:NEJM 2006;353:2643
Holman etal:NEJM2008;359


(.)
5800 ..
Fu = 2 ( )

(%)

M. Busko, Medscape 2009

 (HbA1C)
( 3 4)
23296 Fu = 4

Arch. Intern. Med. 2011;171:1920-1927


ADA 2012
1C

< 7,0 %
70 130 mg/dL (3,9-7,2 mmol/L)
< 180 mg/dL (< 10.0 mmol/L)

:

/

CVD
/

1C A1C

Diabetes Care 2012;suppl.1: s11-s63



ADA 2012,2013

HbA1c <7%
ADA: A

HbA1c <7%
ADA: B

,
CVD

HbA1c <6.5%
ADA: C

, HbA1c <8%

ADA: B


Diabetes Care 2012;35:Suppl.1
Diabetes Care 2013;36:Suppl.1

,
ADA EASD Position statement 2012

H -

IGT

350

300

(mg/dl)

250

200
150
100

50
250

(%)

200
150
100

50
0
-10

-5

10

15

20

25

30

Adapted from Bergenstal RM, et al. Diabetes mellitus, carbohydrate

metabolism and lipid disorders. In Endocrinology. 4th ed. 2001.

():


Statement ADA & EASD 2006,2008

+ Metformin

-
*

+ +/-

Diabetes Care 2006; 29 :1963 -72

Consesus Statement ADA & EASD 2008. Diab. Care 2008; 31: 1-3

 ..2:

HbA1c 1,5-2,0%

( , ,

( - 5-20%)

12

(35% - UKPDS)

Diabetologia 2000; 43: 558-560

 2
ADA, EASD 2006,2008
( )
Metformin
2

2
Metformin

A1c<7%

8%
7%
6%

HbA1c %

9%

10%

10

15

8%
7%
6%

HbA1c %

9%

10%

10

15

,
ADA EASD Position statement 2012

 2:

(-)

GIP

GLP-1

(-)

GLP-1=glucagon-like peptide-1; GIP=glucose-dependent insulinotropic polypeptide.

Brubaker PL et al. Endocrinology 2004;145:26532659; Zander M et al. Lancet 2002;359:824930; Ahren B. Curr Diab Rep 2003;3:365
372; Buse JB et al. In Williams Textbook of Endocrinology. 10th ed. Philadelphia, Saunders, 2003:14271483; Drucker DJ. Diabetes
Care 2003;26:29292940.

33

 GLP-1



A] Glucagon-like peptide-1 *
Liraglutide
GLP-1*
Exenatide

B] IV
(DPP-IV)**
Sitagliptin

Vildagliptin

* -

Saxagliptin

**

TZDs

( DPP-4
GLP-1)

Lancet 2011;378:182-197

 vs
DPP-4
Sus
-
-
-

SU
Sus
-

-
-
- CV (?)

DPP-4
-
-
-
-
- CV
-
-

DPP-4i

DPP-4
- < 5
-

Curr. Diab. Rep 2011;11:83-90

 metformin: DPP-4
vs sulfonylurea. O HbA1c
6 RCTs

BMJ 2012;344:e1369

 vs

Lancet published on line June 28, 2012


UK based GP Research database. 27457
HR 1.57

HR 1.45

HR 0.70 HR 0.76

HR 1.32

HR 1.44

HR 1.38

HR 0.74

C. Morgan et al J. Clin. End.Metab. Decem. 2012

 CV


( )

(95%
CL)

vans
et al 2006

5308

373

2248

38

4,16 (2,971 5,83)

Johnson
et al 2005

2899

320

862

61

1,56 (1,17 - 2,07)

Schramm
et al 2011

57,757

3942

42.513

827

3,51 (3,25 - 3,79)

Schramm
et al 2011

5278

961

2737

169

2,95 (2,49 3,49)

Sillars
et al 2010

396

137

503

81

2,15 (1,58 2,91)

2,72 (1,95 3,79)

Forst et al Diab. Vasc. Dis. Res. 2013;10:302-314

 RCTs

Y. Seino et al Journal of diabetes investigation 2013;4(2):108

SAVOR TIMI33 study

SAVOR TIMI33 study

Primary end points:

A composite of cardiovascular death, nonfatal
myocardial infarction, or nonfatal ischemic
stroke.

Secondary end points:

the primary composite end point plus
hospitalization for heart failure, coronary
revascularization, or unstable angina.

Saxagliptin vs placebo:
SAVOR-TIMI 53: 16492 CVD , Fu= 2,2

B. Scirica et al NEJM September 2, 2013

SAVOR TIMI 53:

B. Scirica et al NEJM September 2, 2013

EASD 2013-Comments

The presentations "would not deter me" from using DPP-4

inhibitors in those with heart failure. "If anything, I
would say this applies to saxagliptin and not to
alogliptin; I would keep an eye on saxagliptin. But
heart failure didn't contribute to the mortality rates at
all.
Prof. J. Holst

SAVOR TIMI 53:

B. Scirica et al NEJM September 2, 2013


Consensus Statement ADA EASD 2009
1: ( )
:

Lifestyle
+
Metformin

Lifestyle

Lifestyle + Metformin
+
Basal Insulin

+
Metformin
+
Intensive
Insulin

Lifestyle + Metformin
+
Sulfonylurea

2: ( )
Lifestyle + Metformin
+ Pioglitazone

/.

Lifestyle + Metformin
+

GLP-1


/

Lifestyle +
Metformin
+
Pioglitazone
+
Sulfonylurea*

Lifestyle +
Metformin
+
Basal insulin

Nathan et al, Diabetologia, on line 2008, DOI. 10.1007/s00125-008-1157-y

 AACE 2009
1C 6.5-7.5%

GLP
+ DPP4 TZD

TZD DPP4 AGI

MET

SU

MET

TZD

+ TZD

MET

+ GLP DPP4

+ AGI

MET

GLP
DPP4

+ D

SU

TZD

MET

GLP DPP4

+ GLP DPP4
TZD

HbA1c <6.5%

MET
GLP-1
DPP4

GLP
DPP4

GLP DPP4
SU

1C > 9.0%

1C 7.6-9.0%

TZD
SU

2-3

American Association of Clinical Endocrinologists: Endocr Pract Oct 2009

ADA EASD Position statement 2012

-
Position Statement ADA EASD 2012


2
HbA1C>9%

ADA/EASD

Diabetes Care 2012:35;1364-1380

Diabetologia 2012:55;1577-1597

 position statement
ADA & EASD

HbA1c 3

SU

TZD

DPP-4

GLP-1

5 :

- - - -

Inzucchi S.E. et al. Diabetes Care 2012;35(6):1364-1379


Position Statement ADA EASD 2012

Diabetologia 2012

-
Position Statement ADA EASD 2012

Diabetes Care 2012:35;1364-1380

Diabetologia 2012:55;1577-1597

Diabetes Care 2012:35;1364-1380

Diabetologia 2012:55;1577-1597

 ADA/EASD 2012
2:

?

GLP-1 Agonist
A-DPP-4
HbA1-c<7%

+-DPP-4 GLP-1 Agonist

 ADA/EASD:
2012

: CVD-UKPDS
? : CVD

?:
precoditioning

 ADA/EASD 2012

:

>1,5(1.4)
GFR<30.

: ()

-DPP-4 :
GLP-1 Agonist: GFR<30.
Diabetes Care 2012:35;1364-1380

Diabetologia 2012:55;1577-1597

 ADA/EASD 2012

:
.
Diabetes Care 2012:35;1364-1380

Diabetologia 2012:55;1577-1597

Position statement ADA/EASD 2012:

( HbA1c > 9,0%)


basal basal bolus,

Diabetes Care 2012:35;1364-1380

Diabetologia 2012:55;1577-1597

ADA-EASD:
2

...
,

.

.
, ,
.

.

.

Diabetes Care, Diabetologia. 19 April 2012

,
ADA EASD Position statement 2012
2013,CE 2013

http://www.ede.gr

2011

 2
HbA1c > 8.5%
(
)

HbA1c 8.5%

&
+

+2

&
+

HbA1c
2- 3

HbA1c
2- 3

HbA1c <8.5%

&
+

+2

+
3

2011

HbA1c
2- 3

HbA1c >9%
( )

&
+

HbA1c >8.5%

&
+


2013

SU

TZD

DPP-4

GLP-1

SU
+
TZD
DPP-4
GLP-1

TZD
+
SU
DPP-4
GLP-1

DPP-4
+

SU

TZD

GLP-1
+

SU

TZD

TZD

DPP-4

GLP-1

CE 2013

,
ADA EASD Position statement 2012
2013,CE 2013

 colesevelam vs placebo
bA1c baseline
6 FU= 24

C.P. Ooi et al Diabet. Med. 2013

 colesevelam vs placebo
baseline
6 FU= 24

C.P. Ooi et al Diabet. Med. 2013

 colesevelam vs placebo
LDL baseline
6 FU= 24

C.P. Ooi et al Diabet. Med. 2013

 SGLT -2

. Diamant et al Lancet July 2013

. Donath et al Diabetes Care 2013;36(suppl. 2): s142

 (Metformin + exenatide + pioglitazone) vs

(metformin + + )

155
Open label controlled
5 , HbA1c = 8,6 %,
46 , BMI = 36 kg
H 3 (. 3) ,
(. ..)
3
. .

2 :
HbA1c

6%

6,6%

p< 0,001

- 1,2kg

+ 1,2kg

p < 0,001

17%

42%

p < 0,001

15%

46%

p < 0,001

5,3%

1,3%

p < 0,05

Ghani et al ADA 2013, ab 72-02



Sulfon.
GLP-1

GLP-1

TZDs

SGLT-2I
GLP-1

TZDs
MET
GLP-1

TZDs
GLP-1

GLP-1
R. DeFronzo et al Diabetes Care 2013;36(suppl.2): s127

1. Gerstein HC et al N Engl J Med. 2008;358: 2545-2559 2. Skyler JS et al Diabetes Care. 2009;32:187-192 3. Blonde L et al Diabetes Obes
Metab. 2009;11(6):623-631 4. Monnier L et al Diabetes Care. 2003;26:881-885 5. Buse JB et al Ann Intern Med. 2011;154:103-112 6. DeVries JH
et al Diabetes Care. 2012;35:1446-1454 7. Raskin P et al Diabetes Care. 2005;28:260-265 8. Merck & Co., Inc. Januvia (sitagliptin) summary of
product characteristics. Available at: http://www.medicines.org.uk/emc/medicine/
19609/SPC/. Accessed October 26, 2012 9. Inzucchi SE et al Diabetologia. 2012;55:1577-1596 10. American Diabetes Association Diabetes
Care. 2011;34(Suppl 1):S11-S61 9. Miser WF et al Clin Ther. 2010;32:896-908

,
ADA EASD Position statement 2012
2013,CE 2013



Metformin

Sulf.

Glitazones

Insulin

Glp-1

DPP-4

++

++

++

+++

++

()



, .

 ... ;

,
.
, .
,
.

 ... ;

.
.
; .

 ... ;

, .

,
. .

, .
, GLP-1 !

. ;

68 , 2 14, + .
, . , Ca 6.
, Ca . BMI: 41.3, 2+ ,
. 150 170 mg/dl, HbA1c 9.8%, eGFR 44,
LDL 122, TG 358, HDL 31, 40 mg. ;
; ;

 :
<7%.!!!

(
)

<7%

(
)

S. Dali:

 !!!!

LDL.



Statement ADA 2013

<140/ 80 mmHg ()

LDL

<100 mg/dl ()
.LDL
>40+ .. ()

LDL>100 . ()

-<150 mg/dl

DL

DL>40 mg/dl () >50 mg/dl ()

:75 -162 mg/ . >50

() >60 () 1
) (C)

- 1C <7%
1C (<6%)

(25)

5-7%

150 min/ .
90 min/ .



Steno2 Study

. Risk reduction : 50%

NNT:5

Goede P et al. NEJM 2003; 348: 383-393.

Glycaemic, lipid and blood pressure control in 1998

and 2006 in Greek diab. Population
[Data are shown as mean value (SD)].

1998

On target

2006

On target

HbA1c (%)

8.1 (2.0)

36.1%

7.0 (1.2)

56.1%

< 0.001

SBP (mmHg)

139.3 (17.9)

22.5%

134.9 (18.7) 35.5%

< 0.001

DBP (mmHg)

80.9 (8.7)

23.0%

77.6 (9.8)

48.2%

< 0.001

HDL-C (mmol/l)

1.2 (0.3)

50.5%

1.3 (0.4)

52.3%

0.002

LDL-C (mmol/l)

3.9 (1.1)

10.4%

2.9 (0.9)

40.2 %

< 0.001

TGL (mmol/l)

2.0 (1.3)

53.6%

1.7 (0.9)

59.9%

< 0.001

All 3 targets: 12%

Liatis et al, Exp Clin Endocrinol Diabetes 2009




DCCT

EDIC

UKPDS

UKPDS
F/U

ACCORD

ADVANCE

VADT

27

34

54

62

62

66

60,4

2,6/~8

~12

~10

10

11,5

+/-

100%

100%

42%

64%

77%

40%

90%

6,5

~10

3,5

~5

11

~10

+++

+++

++

++

0
(41%
S)

+++
(4256%)

0
(16%
NS)

++ (15%)

CVD

ADA/EASD 2012

M. Stumvoll et al Lancet 2005;365:1333-46

What my friends think I do What my mom thinks I do

What society thinks I do

DOCTORS IN GREECE

What government thinks I do

What I think I do

What I really do


10 2000-2010
UK based GP research database 27457

C. Morgan et al J. Clin. End.Metab. Decem. 2012


1997-2000 2006-2008
USA

Am. J. of Medicine 2012;125:e11-e12

1 2 ( 25 -30) 1 5
( > 30)1
4 10
2
754.000 . (8,8%
)3 ( 2009)
, 634.000 (7,4% )
( -)3
6.542 3
4 4
2 ( 80 90%
). 8 10 4.
24 30% 2
5.

1.
2.
3.
4.
5.

International obesity Task Force, http://www.iaso.org//iotf/obesity/

P. Farajian et al. Atherosclerosis, 2011
International Diabetes Federation, IDF Diabetes Antlas, 4th ed. 2009
http://www.euro.who.int/_data/assets/pdf_file/0003/98391/E93348.pdf
DB. Panagiotakos et al (2005) The epidimiology of type 2 diabetes mellitus in Greek adults: the ATTICA study.
Diabet. Med. 22(11):1581-8

,
1,2
1,2:
40%
12%
23% 44%

68%
52%

8,5 17,5% ,
2
12%
1 2,4 20103
25% 75%
4
7% 55%
4

1.
2.
3.
4.
5.

International Diabetes Federation, IDF Diabetes Atlas, 4 th ed. 2009

International Diabetes Federation. IDF Diabetes Atlas, 3 rd ed. 2006
B. Jonsson (2002) Revealing the cost of Type II diabetes in Europe, Diabetologia 45(7):S5-12
Kanavos et al: Diabetes expenditure, burden of disease in 5 EU countries. August 2011
Athanasakis et al. Diabetic Medicine 2010;27:679-684

4,8 470
USD 2012
1000

 metformin: DPP-4 vs sulfonylurea.

O HbA1c
6 RCTs

BMJ 2012;344:e1369

 vs

Lancet published on line June 28, 2012