2014;

. .

&

..
E
(....)

()

2 85-95%

2035
> 592

400

2013
382

350
300
250

2000
150

200
150
100

1985
40

50
0
1985

1990

1995

2000

2005

2010

2015

2020

2035

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

Trends in diabetes mellitus prevalence in adults 20 years of age

by sex (National Health and Nutrition Examination Survey:
19881994 and 20072010).

Alan S. Go et al Circulation. 2014;129:e28-e292


2012

. Dall et al Diabetes Care 2014;37:3172-3179


Centers for disease Control and prevention (CDC)

National Health Interview (NHIS)

National Death Index 1985-2011

2000 2011
lifetime 39,6%
lifetime 40,2%

40%

Lancet Diabetes and Endocrinology

August 2014

Diabetes mellitus awareness, treatment, and control in adults 20 years of

age (National Health and Nutrition Examination Survey: 20072010

Alan S. Go et al Circulation. 2014;129:e28-e292

52

12%

24%

40% -2
65%


U.K. Primary Care Database: 87098 (21798 II, 65300 normal)
2004-2010

R= 2,13
R=2,42

R=3,23
R= 4,7

K. Taylor et al Diabetes Care 2013;36:2366-2371

DCCT

Kumamoto

UKPDS

9 7.2%

9 7%

8 7%

63%

69%

17-21%

54%

70%

24-33%

60%

65%

41%

16%*

HbA1C

*p=0.052

UKPDS: 10 ( 20 ),
CVD

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
.

 CVD DCCT-EDIC
DCCT: 6,5 , EDIC: 12
CVD endpoints
42%:
p = 0,01

MACE

57%:
p = 0,01

J. Lachin et al Diabetes Care 2014;37:39-43

(-)

(-)

. Raz et al Diabetes Care 2013;36:1779-1788

-
Position Statement ADA EASD 2012

-
-
-

Inzucchi SE et al. Diabetes Care. 2012, 35:1364-1379.

Inzucchi SE et al. Diabetlogia. 2012, 55:1577-1596.



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

TZDs

( DPP-4
GLP-1)

Lancet 2011;378:182-197


. BARI2D

. Althouse et al Diabetes Care 2014

 vs :

56536 . Fu=8

HR= 0,33

J. Yang et al Current Medical Research & Opinion July 2014



] IV (DPP-IV)**
Vildagliptin
Sitagliptin
Saxagliptin
Linagliptin
] Glucagon-like peptide-1 *
Liraglutide
GLP-1*

(Exenatide)

**

Characteristics of DPP-4 inhibitors: Differences

in dose, half-life, metabolism and elimination
Compounds t1/2

DPP-4 inhibitors

Metabolism

Elimination route

Sitagliptin
(100 mg qd)

~ 121/2 h

Max. ~97%;
> 80% 24 h postdose

Not appreciably
metabolised

Renal

Vildagliptin
(50 mg bid)

~ 2h

Max. ~ 97%;
> 80% 12 h post
dose

Inactive metabolite
(hydrolysis, in
kidney, liver,
elsewhere: p450
independent)

Metabolism (parent)
Renal
(parent and
metabolite)

Saxagliptin
(5 mg qd)

~ 21/2 h (parent)
~ 3 h (metabolite)

Max ~80%;
> 70% 24 h postdose

Active metabolite
(hepatic, via p450
3A4/5)

Metabolism (parent)
Renal
(parent and
metabolite

Alogliptin
(25 mg qd)

~ 21 h

Max ~90%
~ 75% h post-dose

Not appreciably
metabolised

Renal

Linagliptin
(5 mg qd)

~ 12 h ( effective 1%)
~ 100 h (terminal
1%)

Max ~ 90%
~ 85% 24 h postdose

Not appreciably
metabolised

Biliary
(< 6% via kidney)

Deacon Diab. Obes. Metab. 2011

 RCTs

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

SAVOR TIMI33 study

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

 NYHA baseline
saxagliptin vs placebo
SAVOR TIMI 53

Benjamin M. Scirica et al Circulation. published online

September 4, 2014

SAVOR TIMI 53:

B. Scirica et al NEJM September 2, 2013



A] Glucagon-like peptide-1 *

Liraglutide
GLP-1*

Exenatide BD QW
Lixisenatide

* -

 GLP-1

Exendin-4,
-
50%
GLP-1. DPP-IV.
In vivo x 3-4 h.
, HbA1c
20gr (-0,69%)
(-0,75%).
HbA1c 0,7-1,0% 1-3 kg

,
&
[Distiller LA et al. Diabetes, 2008;
57 (suppl. 1): A154-A158]
: 25% 35%
2,5% ( 7,9%
)

Meier JJ. Nat. Rev. Endocrinol 2012; 8: 72842.

Lixisenatide vs Liraglutide.:
profile

Geremia B. Bolli et al Diab. Obes. Metab. December 24, 2013

Lixisenatide vs Liraglutide:
28

C. Kapitza et al Diabetes, Obesity and Metabolism 2013;15:642-649

 (ORs)
2 RCT

J. Meier et al Diabetologia 2014;57:1320-1324

Exenatide QW

 Exenatide QW
Exenatide QW
()
:




,

-
Exenatide QW
2

Medisorb
CO2 1
1
2
2
67 2

Medisorb is a registered trademark of Alkermes, Inc.

1. DeYoung MB, et al. Diabetes Technol Ther 2011;13:114554.
2. Kim D, et al. Diabetes Care. 2007;30:148793.

H Exenatide QW

, HbA1c

1,3% 1,9%
4 *

<1%



(5%
ExQW)
(, , )
* H Exenatide QW ,
. Exenatide QW ,

.

H 8

218 RCTs 77950

. Esposito et al Diab. Obes.& Metab. 2012;14:228-233

 SGLT-2

. olitch Am. J. Manag. Care 2013;19:s133-s142

 - SGLT2

Hediger MA, Rhoads DB. Physiol. Rev. 1994;74:993-1026.

 SGLT-2
vs placebo:
HbA1c
45

D. Vasilakou et al Ann. Intern.

Med. 2013;159:262-274

 SGLT-2 vs :

45

D. Vasilakou et al Ann. Intern. Med. 2013;159:262-274

SGLT-2

 Liraglutide 3mg
SCALE study

3731
.
500cal. /. 2:1 Liraglutide
3mg vs placebo. Fu = 56
Lira. 8% 2,6%
. Placebo 4,2 cm
( 2,5cm placebo)
Lira
(LDL, HDL)

ICE/ENDO 2014

 ( FDA)

JAMA 2014;312:955

Sept.2014

 :
Degludec PEGylated lispro
Degludec

PEG - Lispro

A. J. Garber Diabetes, Obesity and Metabolism 2014;16:483-491

 profile Degludec

A. J. Garber Diabetes, Obesity and Metabolism 2014;16:483-491

Degludec ( ) vs Glargin:

BEGIN:FLEX T1: 52 Fu

C. Mathieu et al JCEM 2013

Degludec vs glargine:
BEGIN: FlexT1

C. Mathieu et al JCEM 2013;98:1154-1162

liraglutide vs insulin
degludec vs Deglira in
type 2 diabetes
DUAL-1

DUAL I shows substantial improvement in HbA1c with a low risk

of hypoglycaemia with IDegLira compared to insulin degludec

Buse et al. ADA 2013, 65-OR (Trial:

NN9068-3697)

Adding liraglutide or
rapid-acting insulin to
insulin degludec in
type 2 diabetes

Extension trial shows significantly less confirmed hypoglycaemia with

insulin degludec + liraglutide vs. insulin degludec + insulin aspart

C. Mathicu et al Diabetes Obes Metab. 2014 Jan 20.

 GLP-1 vs basal bolus

C. Eng et al Lancet Sept. 12, 2014

GLP-1 +
vs basal bolus:

C. Eng et al Lancet Sept. 12, 2014

GLP-1 +
vs basal bolus:

C. Eng et al Lancet Sept. 12, 2014

Editorial
It has been a 20-year journey, but
the combination of GLP-1 agonist
and basal insulin has finally
arrived as a more powerful and
safer alternative to insulin in the
management of type 2 diabetes
L. A. Young, J. B. Buse

Lancet Sept. 2014

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

The MiniMed Paradigm REAL-Time System

,
,
(SenSerter).

, ,

72 (3 )

,
2 .

 closed-loop
( )

. Atkinson et al Lancet July 26 2013

Russell SJ et al Outpatient glycemic control with a bionic pancreas in

type 1 diabetes. N Engl J Med 2014

 vs :
5

S. Russel et al NEJM June 2014

Sierra Sandison, Miss Idaho 2014

NM504:

504: ,
30 .
504 Placebo 28

. Heiman ICE/ENDO 2014

To

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

FX. Pi- Sunyer Postgrad Med 2009;121:94-107
A. Pater et al Lancet 2007;370:829-840



Statement ADA 2014

<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/ .

 CVD
PREDIMED study: 7447 . Fu= 4,8

R. Estruch et al NEJM 2013

 CVD

PREDIMED study: 7447 , Fu=4,8

R. Estruch et al NEJM April 2013

Da Qing Diabetes prevention study:

6 + 23 Fu:
H

Intervention group

G. Li et al Lancet Diabetes Endocrinol JUN.2014


CVD
HUNT study: 53837 , Fu = 12

B. Moe et al Diabetlogia 2015;1:59-66

S. Dali:

 !!!!!!

 !!!!!!