, 2.3.

2014

2013

2013

 2.....

....

ADA-EASD:
2

HbA1c < 7.0% ( 150-160 mg/dl)

<130 mg/dl

<180 mg/dl

- :
(6.0 - 6.5%) ,
(7.5 - 8.0%+) - ,

,
...

Diabetes Care, Diabetologia. 19 April 2012

detemir
glargine

aspart

lispro
glulisine
regular
aspart NPA

lispro NPL

regular


Lispro (Humalog)
~ 4 hr

Aspart
Glulisine

(Regular Actrapid,)

36 hr

(NPH, Protaphane)

814 hr

Detemir ~ 14-18 hr
Glargine ~24 hr

10

12

14

16

18

20

22

24

()
. Rosenstock J. Clin Cornerstone. 2001; 4: 50-64

Lyspro (Humalog)

5-15

30-90

3-5

Aspart (Novorapid)

5-15

30-90

3-5

Glulysine* (Apidra)

5-15

30-90

3-5

30-60

2-3

5-8

2-4

4-10

10-16

glargine (Lantus)

2-4

20-24

detemir* (Levemir)

2-4

6-14

16-20

(Regular, Actrapid)
()

(Humulin ...,
Protaphane)


& (1/):

, .


, .

60-80% 6.

SANNE G., DIABETES CARE, VOLUME 32, SUPPLEMENT 2, NOVEMBER 2009; S253-259

 >70%
2
4-T Study: 1 year results
Proportion of Patients at
HbA1c Level (%)

60

HbA1c 7.0%

HbA1c 6.5%

48.7%

50
41.7%
40
30
20

23.9%

27.8%*

17.0%
8.1%

10
0
Biphasic Insulin (N=235)

Prandial Insulin (N=238)

Basal Insulin (N=234)

For hypoglycaemia considered major (episodes requiring third-party assistance) or minor (<56
mg/dL [3.1 mmol/L]), number of events/patient/year was higher for prandial>biphasic>basalonly treatment groups.
*P<0.001 vs prandial insulin and biphasic insulin (HbA1c 7.0%); P=0.001 vs biphasic insulin (HbA1c 6.5%); P<0.001 vs prandial
insulin (HbA1c 6.5%)

1. Holman RR, et al. N Eng J Med. 2007;357:1716-1730.

 HbA1c
(
) . ;

1.

2. .
3. .
4. GLP-1 .

 .
60
12
40 Levemir
Eucreas 50/1000 Diamicron MRx2
,
,
.

.

.

24 , 3
.

 .
,
70 kg
BMI 26 kg/m2
HbA1c is 9.3%
215 mg/dL
1% ; - , 150/75 mm/Hg

Levemir 40u, Eucreas 50/1000 DiamicronMRx2
Insulin Therapy Management


&
:

220

259

250

170

247

250

245

168

220

248

210

150

 :



stress

/

DF 2007 pp 6-11, DIS Study, DECDE, Framingham,J Clin Endocrinol Metab 2009; 94:1595-1601


. ;
, , ;

;

;

Diabetes Care 2012;35:13641379

Diabetologia 2012;55:15771596

 basal bolus/basal plus

DIABETES CARE, VOLUME 36, SUPPLEMENT 2, AUGUST 2013

()

/
(%)

Mixtard 30
(Novo Nordisk)

70/30

10ml

Humulin M3
(Eli Lilly)

70/30

10ml

Mixtard 30 Penfill
(Novo Nordisk)

70/30

3 ml

Mixtard 40 Penfill
(Novo Nordisk)

60/40

3 ml

Mixtard 50 Penfill
(Novo Nordisk)

50/50

3 ml

Humulin M3 cart
(Eli Lilly)

70/30

3 ml

--: ()

M3-Mixtard 30

= =

()

/ (%)

NovoMix 30
(Novo Nordisk)

70/30

Aspart

3ml

Humalog mix 25
(Eli Lilly)

75/25

Lispro

3 ml

Humalog mix 50
(Eli Lilly)

50/50

Lispro

3 ml

 &

Humalog Mix 25-50

Novo Mix 30 Flex Pen

Humalog-Apidra-Novorapid

= =

 bA1c 8.5%

.

25/75 30/70
40/60 50/50
.

 .
;

20
10-0-10 ()

0,2-0,3

,




, 3



NovoMix 30 Humalog Mix 25

2 U 3

2 U 3

 65 , 30
30 .
11 1
2
.
;
1. ,

2. (BASAL-BOLUS)
3.

4.

 Humalog Mix25 (1-3

/) = basal bolus (1-5 /
)

K. Bowering et al. Diabet Med, Accepted Article May 2012, doi: 10.1111/j.1464-5491.2012.03722.x
liveira J et al., ADA 2010;628-P

 PARADIGM

 Humalog Mix25 (1-3

/) = basal bolus (1-4 /
)

K. Bowering et al. Diabet Med, Accepted Article May 2012, doi: 10.1111/j.1464-5491.2012.03722.x
liveira J et al., ADA 2010;628-P

Insulin Lispro Mix 25 (LM25) vs Basal/Bolus Therapy (BBT):

HbA1C 48
Mean HbA1c at baseline was
8.93% in the Premix arm and
9.08% in the Basal+ arm

G+L=insulin glargine+insulin lispro; HbA1C=hemoglobin A1C.

Diabetes Care Publish Ahead of Print, published online October 29, 2013
, 2013

Prandial Premixed vs. Basal/Bolus

Therapy (BBT): Hypoglycemia

Hypoglycemia incidence (%)

80

GL n=178
PP n=179

70
60
50

40
30
20
10

Overall Nocturnal Severe

GL=insulin glargine once daily alone or plus 3 mealtime insulin lispro; PP=premix progression (insulin lispro mix 50
once up to thrice daily).

Derived from Jain et al. Diabetes Obes Metab 2010;12(11):967-75

4T study: 1

Holman et al. N Engl J Med 2007;357:171630

Percent of Patients Reaching HbA1cTarges at Week 48

48,2%

HbA1c < 7 %

HbA1c < 6,5 %



HbA1c
8.5
(%)

FPG
9.6
(mmol/l)

PPG
12.6
(mmol/l)

Weight
85.8
(kg)

Hypoglycaemia
grade 2 or 3
(events/patient/year)
25
20
15
10
5
0

p<0.001

p<0.001

P<0.001

p<0.001

p=0.04

20
10
0
-10
-20
-30
-40

N Engl J Med 2007; 357: 1716-30

A1chieve study:

insulin nave

14.5

insulin users

8.3
Aspart

//

Basal +
Aspart

8.0

3.5

7.0
6.5
3.0

3.0

Detemir

Biphasic
/Premix

4.0

2.5
2.0
1.7
1.6
1.5

4.1

4.0

1.3
1.1
0.9

1.1
1.0
1.0
0.5

0.0

6.0
5.5
5.0

3.0
2.0
1.0

baseline

24 weeks

0.0 baseline

1. Home P, Naggar NE, Khamseh M, et al. Diabetes Res Clin Pract 2011;94(3):35263
2. Shah S, Zilov A, Malek R, et al. Diabetes Res Clin Pract 2011;94(3):36470

2.7
1.8
1.8

24 weeks

Levit S et al. Horm Int J Clin Pract 2011 65:165-171

 3 .
Median 95% confidence interval

Biphasic
prandial

Prandial
basal

Basal
prandial



(08.00)

2hrs

78

115

(14.00)

(21.30)

2hrs

2hrs

145

295
194

143

198

154

3
4
5
6
7

80

121
165

75

296

126

156

388

Lantus
40

ix25

Humalog Mix50


H Humalog Mix50 x 3
basal-bolus, 1 + 3
: Humalog Mix50 / + Humalog Mix25

Clinical Therapeutics, Vol. 33, No 5, 2010 Substudy of the DURABLE Trial, Diabetes Care 31: 20-25, 2008

 -

,
.
,
( ) .
,
.

 Basal-plus

asal plus

 ;
Basal plus basal bolus

basal-bolus

Humalog Mix25:
bA1c

Giugliano D et al., Diabetes Care 2011;34:510517


69
16
:
Lantus 46 iu

+ 1700 mg
+ 6 mg
HbA1c = 8,7%
: 85-128, 2h+: 257
2


(08.00)

2hrs

113

164

(14.00)

(21.30)

2hrs

2hrs

182

278
194

191

3
4

108

200

286

6
8
9

198
118

75/25

36/28

168

5
7

202

HbA1c:
7,6 -> 7,7%

154

180

38/28

258
189

199


2.
3. /