.

, -
, &


2
Long-acting insulin
Degludec
Pegylated lispro
Glargine U300
Concentrated insulin
Degludec U200
Glargine U300
Biodel U400
Lilly U500

Combination insulin
Degludec+Aspart
Degludec+Liraglutide
Glargine+lixisenatide
Rapid-acting insulin
Hyaluronidase+rapid
Inhaled insulin
Fisp (rapid aspart)
Biodel

(FPG)

FPG

 DEGLUDEC

 degludec:

degludec
-

degludec
-
-Zn2+

Phenol;

Zn2+]

+Zn2+

degludec

Jonassen et al. Diabetes 2010;59(Suppl.1):A11(39-OR); Jonassen et al. Diabetologia 2010;53(Suppl.1):S388 (Poster 972)

 degludec:
video

 degludec: &

AUCGIR,06h

AUCGIR,612h

AUCGIR,012h

AUCGIR,1218h

AUCGIR,1824h

AUCGIR,1224h

Heise et al. Diabetes 2011;60(Suppl.1):LB11; Heise et al. Diabetologia 2011;54(Suppl.1):S425

 degludec: 24

Tresiba
0.4 U/kg

0.6 U/kg

IGlar
0.8 U/kg

25.4 h

Heise et al. ADA 2011; 37-P LB; Heise et al. Diabetologia 2011;54(Suppl. 1):S425 (1046-P)

0.4 U/kg

0.6 U/kg

12.5 h

0.8 U/kg

FPGs

130

142

85

180

90

166

75

(?)


/

 , -

NPH (0.4 U/kg)

glargine (0.4 U/kg)
detemir (0.4 U/kg)

Heise et al. Diabetes 2004;53:161420

 degludec:

220

- -
(CV%)

200
180
160
140

Ideg

IDeg IGlar
(p<0.0001)

IGlar

120
100
80
60
40
20
0

GIR ()

GIR,
Heise et al. Diabetes Obes Metab 2012;14:85964

FPG
(mg/dl)

216

216

198

198

180
162

180

Average FPG

162

144

144

126

126

108

108

90
72

90
72

Target zone

54
36

54
36

Hypoglycaemia zone

18

18
1 2 3

10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30

FPG
(mg/dl)

216

216

198

198

180
162

180

Average FPG

162

144

144

126

126

108

108

90
72

90
72

Target zone

54
36

54
36

Hypoglycaemia zone

18

18
1 2 3

10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30

Day

. .
&

..

2
1,5
1

III
II

0,5
I

0
III

II

M-FPG
CV-FPG:
M FPG:
Verona Diabetes Study, Diabetes Care;2001

 ,

10-

1.0

0.9

CV of FPG *

0.8

Group 1 (8.5%)

0.7
Group 2 (14.8%)
Group 3 (27.7%)

0.6

0.5
0

CV =
*Significant differences in the CV of FPG (p<0.001)

Muggeo M et al. Diabetes Care 2000;23:45-50

4
()

10

Verona Study

2 (2013)

2 (2011)


2
Leiter et al. 15%
2

(58%)

Leiter et al.

Leiter et al. Can J Diabetes 2005;29(3):186-92


(continuous glucose monitoring system,
CGMS) /
63% 1,
47% 2
(n=70)

Chico A, et al. Diabetes Care 2003;26(4):1153-1157


(%)

45%

42,0%

40%

35%

30%

23,0%

25%

20%

15%

10%

5%
0%

Brod et al. Curr Med Res Opin, Dec 2012, Vol. 28, No. 12: 19471958

GAPP2:
,

Proportion of patients
(%)

30,0%
25,0%

26%

24%

20,0%

14%

15,0%
10,0%
5,0%
0,0%
Missed a dose

Mistimed a dose

Brod et al. Curr Med Res Opin, Dec 2012, Vol. 28, No. 12: 19471958

Reduced a dose

N Eng J Med 2010;363:1410-8

Risk of Cardiac Arrhythmias During

Hypoglycaemia in Patients With Type 2
Diabetes and Cardiovascular Risk
Chow E, Bernjak A, Williams S, Fawdry RA, Hibbert S, Freeman J, Sheridan PJ, Heller SR

Chow E. et al. Diabetes 2014;63:17381747

90

Mean IG at nadir
50.4 9 mg/dl

72

(mg/dl)

(mg/dl)

90

Mean IG at nadir
34 12.6 mg/dl

72

34 ,
CGM, 3
54
36

54
36
18

18

-50

-40

-30

-20

-10

10

(min)

20

30

-100

-50

(min)

20 11 , 14 10 .
Hypoglycaemic nadir = episode time 0; negative time values = from the beginning of the hypoglycaemic episode to
nadir; positive values = from the nadir to recovery from hypoglycaemia. Data are mean SD.

Chow E. et al. Diabetes 2014;63:17381747

50

Insulin-nave 2: BEGIN ONCE LONG2

HbA1c
Treatment difference:
non-inferior

0.0

Treatment
difference:
0.12%-points (ns)

Extension

Core
26

FPG

65
Time (weeks)

79

91

Treatment difference:
0.43 mmol/L,
p=0.005

0.0
104

Confirmed hypoglycaemia
18% lower rate with
IDeg (ns)

Treatment difference:
0.38 mmol/L,
p=0.019

Extension

Core

26

65
Time (weeks)

79

91

0
104

Nocturnal confirmed hypoglycaemia

16% lower rate with

IDeg (ns)

36% lower rate with

IDeg, p=0.038

43% lower rate with

IDeg, p=0.002

Extension

Core

Extension

Core

Time (weeks)

Time (weeks)

IDeg OD

IGlar OD

Zinman et al. Diab Care 2012;35:246471; Rodbard et al. Diabetic Med 2013;30:1298304

Basalbolus 2: BEGIN BB
HbA1c

FPG
Treatment difference:
non-inferior

0.0

Treatment difference:
0.29 mmol/L (ns)

0.0

26
Time (weeks)

Confirmed hypoglycaemia

26
Time (weeks)

Nocturnal confirmed hypoglycaemia

18% lower rate with

IDeg, p=0.0359

25% lower rate with

IDeg, p=0.0399

Time (weeks)

Time (weeks)

IDeg OD + IAsp

Garber et al. Lancet 2012;379:1498507

IGlar OD + IAsp

BEGIN BB in T1D (long)

Time (weeks)

Heller et al. Lancet 2012;379:148997

FPG (mmol/L)

Treatment difference:
non-inferior

IDeg OD (n=472)
IGlar OD (n=157)

FPG

Treatment difference:
0.33 mmol/L (5.94 mg/dL) (ns)

Time (weeks)

FPG (mg/dL)

HbA1c (%)

HbA1c

BEGIN BB in T1D (long)

IDeg OD (n=472)
IGlar OD (n=154)

Nocturnal confirmed
hypoglycaemia

25% lower
rate with
IDeg,
p=0.021

Time (weeks)

Heller et al. Lancet 2012;379:148997

 FPG
2 BOT
2

82% FPG

Degludec glargine

Zinman et al. Diabetes 2013;62(Suppl. 1):A99(388-P)

22%

Peyrot et al. Diabetes Care 2010;33:2405

GAPP2:

30

Brod et al. EASD 2012; Poster 955

30
=
4.2/

 3
degludec

 degludec:
200

, t1/2 12.5h

180

, t1/2 25 h

160
140
120
100
80
60
40
0
20
08.00

24h

32h

16h

08.00

16.00

24h

24h

24h

08.00

08.00

08.00

08.00




IDeg IDegAsp
, , ,

MACE
IDeg IDeg/Asp
,
FDA

Novo Nordisk

2013: RR 1.081 [0.691;1.692]

 degludec
steady state 23
1

110

110

100

100

90
80
70
60
50
40
30
20
10
0

120
IDeg
Proportion of Day 4 level (%)

IDeg
Proportion of Day 6 level (%)

120

90
80
70
60
50
40
30
20
10

Heise et al. Diabetes 2012;61(Suppl. 1):A259


degludec

10 U

10 U

(t1/2~24 h)

24h

5U

10 U

50%

5U

15 U

50%

7,5 U

10 U

7,5 U

17,5 U

50%

~9 U

10 U

~9 U

19 U

50%

10 U

10 U

10 U

20 U

50%

10 U

10 U

Figure adapted from Heise and Meneghini Endocr Pract 2014;20:7583

 degludec (Tresiba)

FlexTouch

( )
:

,
80 U

FlexTouch

 :
:

FPGs

130

142

85

180

90

166

75

 :
> 6

,
24

()


40% 2
1
21/11/2014: CHMP
2 (
3b LIRA-RENAL)
,
2
.

1 Bailey CJ, Day C. Diabetes therapies in renal impairment. B J Diabetes Vas Dis 2012;
12(4):167-171

IDegLira

DUAL I: HbA1c

HbA1c (%)

IDegLira (n=833)
IDeg (n=413)
Liraglutide (n=414)

HbA1C

EOT

1.28%
1.44%

7.0%
6.9%

1.91%*

6.4%

*p<0.0001 vs. IDeg

and vs. Liraglutide

0.0
Time (weeks)
Mean SEM; FAS; LOCF. --- ADA/EASD HbA1c target <7.0%; AACE HbA1c target 6.5%
AACE, American Association of Clinical Endocrinologists; ADA, American Diabetes Association; EASD, European Association for the
Study of Diabetes
Gough et al. Diabetologia 2013;56(Suppl. 1):S96(OR-219); Buse et al. Diabetes 2013;62(Suppl. 1):A16

5
0

5
1

5
2