.

&


,
.

(2
, SMBG),
(HBA1c).
2/3 24
.

 (UKPDS) 35, 1% A1C

:
21%

14%

12%

37%

(P<.0001)

(P<.0001)

Stratton IM et al. BMJ. 2000;321:405-412.

(P=.04)

(P<.0001)

% of Patienten

IRIS-Study (representative cohort of 4575 type 2 diabetic patients

in Germany): Proportion of patients achieving specific HbA1c targets

18
<6.5%

32
<7.0%

48

61

<7.5%

<8.0%

HbA1c target
Rihl, Biermann, Standl: Diabetes & Stoffw. (2002)11:150-158

 2 (HbA1c <7.0%)

People with diagnosed T2D

(%)

100

P=0.002*
80

60

40

49.5

57.1

35.8

20

1999-2000

2001-2002

2003-2004

*P value was derived from multiple logistic regression models with HbA1c <7.0% as the outcome
variable. Age, sex, race/ethnicity, BMI, and survey were included as independent variables

Ong KL, et al. Ann Epidemiol. 2008;18:222-9.

 2
A1c 8.5%

A1c>8.5%
( )

+ 1

&
+
MET +
MET +

A1c 2-3

A1c<8.5%
1.

, ,
,

2.

3.

A1C> 9%
()

DPP-4 GLP-1
SU GLIN

& + +
+ +/-
(

A1c 2-3

A1c>8.5%

& +
+ TZD + SU
MET + DPP-4 / GLP-1 + SU
MET + DPP-4 / GLP-1 + TZD
2-3
>7%

&
+ +

2011

DIABETES CARE,
VOLUME 35, JUNE
2012

1c 6,5-7,5%

HBA1c 7,6-9,5%

MONO

1 .
2 .,
., ., DPP4,
.,

+ 2

+ 2

.
2 +

3 +

Y

(, ,

, ?)

1..

) :
) - : -
) -: , DPP-4
) : , ?
2.
) - (3 ), - -
,
HbA1-c <7% (6,5%)
3.

4. ,

, ,

-

DPP-4

SGLT2

E, ,

, ,
,

XHMATIKO KOTO


3 2

SUs

TZDs

DPP-4/
GLP1

SUs=, TZD=, DPP-4= -4.

Inzucchi SE. JAMA 2002;287(3):360372; Gallwitz B. Minerva Endocrinol. 2006;31(2):133147.

HbA1c

0.5-0.8%

1-2%

1-2%

/-

1-1.5% 0.5-1.5%

()

1-4

--0.5

+
+
-

+
-

2-10

3.6-5.3

()

+
-

Heine RJ et al BMJ 2006: 333 (1200-4)

1

-

QTc QTd

1. Landstedt Hallin L et al, J Intern Med 1999: (246) 299-307

2. Cryer PE, J Clin Invest. 2007: 117 (4) 868-70

... ?


:



HbA1c

Diabetes Care 33:501

506, 2010

 + 2.0%
SU
GLINIDE
ROSI
PIO
AGI
DPP-4
GLP-1
METFORMIN

MONOTHERAPY
1.25
0.75
1.25
1.0
1.0
0.75
1.0
1.0

+ METFORMIN
0.8

Sherifali Diabetes Care 33:18591864, 2010, Phung JAMA 303:1410, 2010

0.7
1.0
1.0
0.7
0.8
1.0
-21

Effect of Noninsulin Antidiabetic Drugs Added to

Metformin Therapy on Glycemic Control, Weight Gain, and
Hypoglycemia in Type 2 Diabetes

: M

: M
HbA1c<7%

Phung, O. J. et al. JAMA 2010;303:1410-1418.

DeFronzo RA Diabetes 2009; 58: 773-795


53%
Kaplan-Meier event rate of progression to permanent Insulin use
0.25

N events:
0.20

3-year estimate:

placebo

362 / 1737

22.0%

pioglitazone

183 / 1741

11.1%

53%

0.15

0.10

0.05
pioglitazone
vs placebo
0.0
N at Risk: 3478
0

HR

95% CI

p value

0.469

0.392, 0.56

<0.0001

3346

3198

3075

2955

2824

12

18

24

30

446 (137)
36

Proactive study, The Lancet, Vol.366, 8 Oct 2005, Pages 1279-

D. S. H. Bell and F. Ovalle. Diabetes, Obesity and Metabolism, 8, 2006, 110115

 PROactive:

HbA1c <7%
Actos+ Met
Met

6,8%

Actos+ SU
SU

6,9%

Diabet. Med. 26, 12421249 (2009)

Change in HbA1c (%)

Hanefeld (n=250)
Charbonnel (n=317)

Chicago (n=232)
ADOPT (n=1,456)
Rosestock (n=115)
Tan (n=249)

Periscope (n=178)
RECORD (n=301)

PIO

Rosiglitazone

ROSI
PIO

-1

PIO

PIO
0

-2
5 studies in subjects with IGT demonstrated that TZDs prevent the
progression of IGT to Type 2 diabetes
(DREAM, ACT NOW, TRIPOD, PIPOD and DPT)

()
DeFronzo: Diabetes 2009; 58:

Meta-analysis data from 9 clinical studies

Risk ratios for composite end point of CVD hospitalizations or CVD mortality*
Source study reference

Relative risk
(95% CI)

Combination Control
therapy
group

Bruno (1999)

1.04 (0.62, 1.75)

NS

NS

Olsson (2000)

1.86 (1.33, 2.61)

NS

NS

Johnson (2005)

0.96 (0.82, 1.12)

264/1081

541/2138

Koro (2005)

1.38 (1.13, 1.69)

NS

NS

Evans (2006a)

2.24 (1.26, 3.99)

133/1252

229/2286

Evans (2006b)

1.86 (1.03, 3.35)

92/985

229/2286

Evans (2006c)

1.52 (0.84, 2.76)

12/113

229/2286

Overall

1.43 (1.10, 1.85)

0.25
SU combo with met
better than comparators

1.00

4.00

SU combo with met

worse than comparators

CI=confidence interval; CVD=cardiovascular disease; met=metformin; NS=not specified; SU=sulfonylureas

*Composite end point of CVD hospitalizations or CVD mortality only statistically significantly increased end point.
Rao A, et al. Diabetes Care. 2008; 31: 16721678.


.
91.521 1990 2005

37% vs

37% vs

18%-30% (.
) vs

vs

24%-61% (.
) vs

41%
49% vs
(. )

J 2009;
339:b4731

24%-61%
(. ) vs


(General Practice

Research atabase).
.2,

2000-2010. 27.457
. 26.278 (95,7%) 1.000
.

(MACE)

HbA1c
12


*MACE, MI, Stroke, Cancer

Baseline HbA1c, % median

10.0%

8.0%

-1,0%
0,1%

***

12-month HbA1c, % median

-1,0%
***

-0,7%
***

6.0%

4.0%

2.0%

0.0%
Sulf (n=1.348)
*** p<.001

Met + Sulf (n=10.193)

Met + Pio (n=1.738)

Met + DPP4 (n=709)

(HR) (HR 1.459, p<0.001),
(MACE) (HR 1.578,
p<0.002), (HR 1.444, p<0.02) ,
(HR 1.381, p<0.003).

(HR 0.707, p<0.03)

(HR 0.747, p<0.004).

HbA1c ,
.

(NAFLD) (NASH)

: 50-80%
NASH:

NAFLD (): 20 gr /d (1
), C (-), (-)
20-30


: (20-30%
)

: 50-80%
( : 20-50%)

: 20%

NASH: ( 100%
!!!)

Pioglitazone + diet vs diet (6 ) n=55, IGT, NASH

p<0.001

Belfort; NEJM 2006


A
P = 0.002

0.73%

0.16%

41

Diabetes, Obesity and Metabolism, 7, 2005, 675691

Diabetes, Obesity and Metabolism, 7, 2005, 642653

C-reactive protein

(HDL, LDL, TG)
Plasminogen activator inhibitor1 (PAI-1) levels?

UKPDS

(
)

(
HDL, LDL, TG)
M

VSMC

PAI-1
( TNF-a, CRP,
etc.)
Rate of in-stent stenosis
postangioplasty
-

2

 HbA1c
( BMI> 30)

G. Bolli et al. Diabetes, Obesity and Metabolism, 11, 2009, 589595

 (mg/dl)

-18,0 *
-18,0

28,8
*
-28,8

G. Bolli et al. Diabetes, Obesity and Metabolism, 11, 2009, 589595

60 %
50

HbA1c

40
30
20
10

0
Pio+SU

Pio+MET

SU+MET

100

77%

(%)

80

60

54%

40

20

FDC
26%1*
FDC

2

FDC
(n=1815)
(n=105)
T2DM3
FDC= , T2DM= 2
1*P <0,001 .
.
1Bangalore S, et al. Am J Med 2007; 120: 713-719.
2Melikian C, et al. Clin Ther 2002; 24: 460-467.
3Blonde L, et al. Diabetes Obes Metab 2003; 5: 424-431.



30%2

HbA1c

0.5%2

(p<0.0001)

Diabetes Care 25:10151021,482002

1618

.
%
( 1 )

86%

61%

49
Diabetes, Obesity and Metabolism, 11, 2009, 527533


.
,


(HDL, TRG, NAFLD )
() -

()




.
2010

50

63 , 28,5, HBa1c 7,9%, Chol

229mg/dl, Trg 210mg/ dl, HDL 36mg/dl, LDL
104mg/dl, Ht 49%, ,
U/S,
,

5/ , 850mg1
, 3mgX1.

38 ,, 26, HBa1c
8,1%, 135mg/dl SGOT/SGPT
30/64mg/dl, Gt 125mg/dl, Ht 45,8%, Chol
239mg/dl, TRG 209mg/dl, HDL 41mg/dl, LDL
117, 138/88mm/hg.
,
2/
( )
.
-

2/3 .

3 ( /)
.

H. Lebovitz. Compination therapy for hyperglycemia.

In Therapy for DM and repated disorders ,4th edition, ADA 2004