Insulin initiation made safer and simpler (Premix analogue)

Insulin initiation made safer and simpler

(Premix analogue)

2

• Simple convenient meal-time regimen

• 24-hour better physiological control

• High safety

• Once-a-day dosing with OADs gives superior control

• FlexPen – Patient and prescriber acceptance

• NovoMix 30 Vs. Glargine: New data

• Once daily NovoMix 30 with OADs: New study

• High safety: 4 yr data

(Premix analogue)

3


– 3 studies


• High safety



(Premix analogue)

4

NovoMix ® 30 can be given pre- or post-meal (1)

Warren et al. Diabetes Res Clin Pract. 2004 Oct;66(1):23- 9

Preprandial dosing(NovoMix® 30, bid)

Postprandial dosing(NovoMix® 30, bid)

0

20

40

60

80

100

120

140

160

180

200

Before breakfast

Before dinner

2 hrs after breakfast

2 hrs afterdinner

Blo

od

glu

cose

leve

ls (

mg

/dl)

n = 91

p = NS in all cases

•12-wk, crossover, N=92 (elderly) T2DM

(Premix analogue)

Similar BG, given pre- or post meal

Study 1

5

NovoMix ® 30 can be given pre- or post-meal (2)

Blo

od

glu

cose

(m

mo

l/l)

6

2

0

–2

–4

4

Time (min)

0 60 120 180 240 300

NovoMix® 30( t= +15 min)

NovoMix® 30(t = 0 min)

Human Mixtard® 30(t = 0 min)

Human Mixtard® 30(t = –15 min)

Kapitza et al. Diabetic Medicine 2004; 21:500–1

Open-label, crossover trial, N=31, T2DMStudy 2

6

Human Mixtard® 30

NovoMix® 30

Blo

od

glu

cose

exc

urs

ion

4 h

aft

er

inje

ctio

n (

mm

ol.m

in.l-1

)

0

2000

2200

2400

2600

2800

3000

t = 0 t = –30

Injection time in relation to meal

p < 0.0001

23%

p = 0.013

Hermansen et al. Metabolism 2002;51(7):896–900

9%

t = 0

PPG control better than Human Mixtard ® 30 with- or before meal

Randomized, crossover, 3-arm, single dose comparison with Human Mixtard ® 30, T1DM , N=50

(Premix analogue)

Study 3

7

NovoMix® 30 offers simple convenient meal-time regimen – why?

• No waiting period after injection

• Can be taken with or after meal

• No overflow hypo

(Premix analogue)

8



– 3 studies (vs. Mixtard, Lispro Mix, NPH)

• High safety



(Premix analogue)

9

24h improved postprandial glucose after 3 months

*

Blo

od

glu

cose

(m

mo

l/l)

*

0Pre-

10

12

Post-

8

6

NovoMix® 30

Human Mixtard® 30* p < 0.05

*

*

Lunch

Pre- Post-

Breakfast

Pre- Post-

Dinner

Bedtime 0200 h

Boehm et al. Diabet Med 2002;19(5):393–9

European BIAsp 30

study group

(Premix analogue)

12-wk, open-label comparison of NovoMix® 30 bd Vs Mixtard® 30 bd

N= 294, T1 and T2 DM

Study 1

10

NovoMix® 30 produces significantly lower prandial glucose increment than H. Mixtard® 30

0

0.5

1

1.5

2

2.5

3

NovoMix® 30 Human Mixtard® 30

Mea

n p

ran

dia

l glu

cose

in

crem

ent

(mm

ol/

l)

Boehm et al. Diabet Med 2002;19(5):393–399

p < 0.02 between treatment groups

(n = 128) (n = 141)

1.66 mM

2.34 mM

European BIAsp 30

study group

(Premix analogue)

30%

Study 1

11

NovoMix® 30 produces significantly lower prandial glucose increment than Lispro Mix

Hermansen K et al. Diabetes Care 2002;25:883–8

p < 0.05

–10%

p < 0.001

–17%

0

13

14

15

16

17

18

19

20

21

Humalog® Mix 25TM NovoMix® 30 Human Mixtard® 30

Blo

od

glu

cose

exc

urs

ion

0– 5

h (m

mo

l/l h

)

Randomized, crossover, 3-arm, single dose comparison with Lispro Mix and Human Mixtard® , T2DM , N=45

Study 2

12

Greater HbA1c reduction with NovoMix®

30 vs. NPH

NovoMix® 30 NPHC

han

ge

in H

bA

1c (%

)

-1.0

-0.8

-0.6

-0.4

-0.2

0.0

p = 0.03

Christiansen et al. Diab Obes Met. 2003; 5(6) 445-52

16-wk, double-blind, parallel comparison of NovoMix® 30 bd Vs NPH bd

N= 403, T2 DM

(Premix analogue)

Study 3

13

NovoMix® 30 offers 24-hour better physiological control - Why?

• Significantly lower PG increment than human Mixtard®

• Significantly reduced HbA1c levels

(Premix analogue)

14



• High safety

– 3 studies



(Premix analogue)

15

• There were no reports of major hypoglycaemia during the trial

• Lesser number of minor hypoglycaemic episodes with NovoMix® 30

• NovoMix® 30 + met 23

• NovoMix® 30 alone 20

• Met + SU 28

• No other safety concerns were raised

Hypo profile as safe as OADs

Kvapil M et al. Diabetes 2002;51(Suppl 2):A104

16-wk, open-label comparison of NovoMix® 30, NM+Met, Met+SU

N=329

(Premix analogue)

Study 1

16

Low risk of nocturnal hypoglycemia (1)

Nu

mb

er o

f h

ypo

gly

caem

ic e

pis

od

es

0

5

10

15

20

25

30

35

40

45

NovoMix® 30 Human Mixtard® 30

42 events

20 events

50% relative risk reduction

Boehm B et al. Diabet Med 2002;19(5):393–399

(n = 138) (n = 153)

12-wk, open-label comparison of NovoMix® 30 bd Vs Mixtard® 30 bd

N= 294, T1 and T2 DM; RR hypo midnight-6 am = 0.62 (38% reduction)

European BIAsp 30

study group

(Premix analogue)

Study 2

BiAsp-1069

Low risk of nocturnal hypoglycemia (2)

Boehm et al. Diabetologia 2001; 44 (Suppl 1): A210.

0

2

4

6

8

10

12

1st year 2nd year

Year of study

Pa

tie

nts

wit

h a

t le

as

t o

ne

ma

jor

ep

iso

de

(%

)

p = NS

p = 0.04

NovoMix® 30

Human Mixtard® 30

2-year extension of

European trialOnly T2DM

N=125

5%

8%

0%

10%

On correct usage, major hypo can be avoided with NovoMix® 30

(Premix analogue)

Study 3

18

NovoMix® 30 offers High safety – Why?

• Hypo profile as safe as OADs

• Reduced risk of between-meal hypo

• Low risk of nocturnal hypo

(Premix analogue)

19



• High safety


– 2 studies (with Metformin; with glitazone)


(Premix analogue)

20

Metformin combination

Kilo C et al. J Diabetes Compl 2003; 17: 307-13

Ch

ang

e in

Hb

A1c f

rom

bas

elin

e (%

)

NovoMix® 30 better glycemic control than Human Mixtard® 30

Insulin (+metformin)

-3

-2.5

-2

-1.5

-1

-0.5

0NovoMix® 30 NPH Human Mixtard ® 30

US study, 25 centres, N=131, T2 DM, 12 wk

3-arm, open-label comparison of Metformin plus once-daily NM, Mixtard, NPH

(Premix analogue)

Study 1

21

Glitazone combination

Raz I et al. Diabetologia 2003;46(Suppl 2):A8

Hb

A1c

(%

)

7.0

7.5

8.0

8.5

9.0

9.5

10.0

10.5

11.0

Screening Visit 6 End of Trial

NovoMix® 30

NovoMix® 30 + pioglitazone

Glibenclamide + pioglitazone

* *

*p < 0.01

N=246, T2 DM OAD failure, 18 wk

3-arm, open-label comparison of NM+Pio, NM alone, SU+Pio

Replace SU/SU+combn failures with NovoMix® 30+Pio in T2DM

(Premix analogue)

Study 2

22

NovoMix® 30 offers once-a-day dosing with OADs and gives superior control – Why?

• NovoMix® 30 better glycemic control than Human Mixtard® 30 when combined with OADs

• Replace SU/SU+combn failures with NovoMix® 30+Pio in T2DM

(Premix analogue)

23



• High safety



– 1 study

(Premix analogue)

24

N=102

82% of healthcare professionals preferred FlexPen® compared to two other prefilled pens2

0

20

40

60

80

100

FlexPen® Lilly pen

82%

14%3%

Aventis prefilled pen

Patient and prescriber acceptance (1)

%p<0.01 vs. Lilly pen and Aventis pen

Lawton et al. Diabetes 2001; 50 (suppl 2): A440

(Premix analogue)

Study 1

25

How can you say that NovoMix® 30 FlexPen enjoys patient and prescriber acceptance?

• Studies have shown that > 80% healthcare professionals preferred NovoMix FlexPen

(Premix analogue)

26

• Patient profile for NovoMix® 30

(Premix analogue)

27

NovoMix 30: What are the patient profiles?

NM30 is suitable for following 3 sets of pts.

• Elderly (50 yrs) people with type 2 diabetes

• Uncontrolled diabetes in people on conventional insulins

• People with diabetes prone to or with fear of hypoglycemia

28

How to use NovoMix® 30?

• Initiation of NovoMix® 30:

1) 0.2 U/kg/24 h

2) Split 2/3 morning, 1/3 evening

3) Keep OAD dose unchanged

• Switching from Human Mixtard 30 or NPH: Dose 1:1

(Premix analogue)

29

NovoMix 30: Kinetics

Human Mixtard ® 30

within 30 minutes

2-8 hours

24 hours

NovoMix® 30

10-20 minutes

1-4 hours

24 hours

Onset of action

Peak action

Duration of action

30

NovoMix 30 vs. Glargine : New data

31

NovoMix 30 vs. Insulin Glargine (1)

1. NM30 provides both basal & prandial control (Glargine provides only basal control- controlling PPG is important)

2. NM 30 - mitogenicity similar to HI; Glargine – 8-fold increased mitogenicity

3. Retinopathy seen in some patients with type 2 diabetes in studies of 1 year or shorter

Berger M. Lancet 2000;356:2013-4

4. 2 studies presented at ADA ‘04 -NovoMix 30 is superior to Glargine

• INITIATE study

• Luzio et al. study

32

NovoMix 30 vs. Insulin Glargine (2) INITIATE study

• INITIATE = INITiation of Insulin to reach A1c TargEt

• Twice daily NovoMix 30 vs. Bedtime Insulin Glargine

Raskin et al. Diabetes June 2004; 53 (Suppl. 2): A143

Study highlights •US multicentre, randomized, • n=233 type 2 DM inadequately controlled on OAD• Duration= 28 wk.•OAD: Pts discontinued SUs, Stabilized on met

If on glitazones, continued on Pio

33

NovoMix 30 vs. Insulin Glargine (3)

NovoMix 30 is superior to Insulin Glargine

1. Better overall control - lower HbA1c

2. Better PPG control

3. More patients achieved target HbA1C of ≤ 6.5% or <7%

34

NovoMix 30 vs. insulin Glargine (4) Better PPG control than Glargine


Befor

e br

eakfa

st

Breakfa

st +90

Befor

e lun

ch

Lunch +

90

Before dinner

Dinner +90

Bedtime

2 am

35

NovoMix 30 Vs. Insulin Glargine (5)

01020304050607080

<6.

5%<7%

NM 30 Glargine

HbA1c target

More patients achieved target A1C with NM30


Pati

ents

reach

ing t

arg

et

at

week

28

(%

)

42%

28%

66%

40%

p=0.0356

p=0.0002

36

NovoMix 30 vs. Insulin Glargine (6) Luzio et al.

NovoMix® 30 or glargine

NovoMix® 30

0

50

100

150

200

250

300

350

400

-1 4 9 14 19 24

Time (h)

Pla

sm

a I

ns

uli

n (

pM

)

NovoMix® 30

GlarginePI AUC0-24h; p<0.01

Luzio et al. Diabetes June 2004; 53 (Suppl 2): A136

1. Compared PK & PD of NM 30 vs. Glargine

2. 28% greater pl. insulin (AUC) 3. 34% greater glucose-lowering effect

37

NovoMix 30 Vs. Insulin Glargine (7) Luzio et al.

• Although equivalent doses of NM30 & Glargine were given:

– 28% greater plasma insulin (AUC) with NovoMix® 30

– In contrast to Glargine that targets only basal control, NM targets clinically important PPG + good basal control

– 32% greater glucose-lowering effect with NovoMix® 30

38

Once daily with OADs: New study

39

NovoMix: Once daily when initiated, enabled 42% to achieve target HbA1c (1)• Jain et al.; presented at ADA ‘04• Phase 1 of 48 wk, multicenter trial• Subjects not achieving targets on OAD with or without once daily basal insulin

(NPH/Glargine) • of the 92 patients, at 16 wks

– 23% (21) achieved A1C ≤ 6.5%

– 42% (39) achieved A1C < 7%

– For subjects who achieved A1C ≤ 6.5%, mean A1C reduction was 2.4%

Baseline At 16 wks

8.5% 6.1%2.4%

Jain et al. Diabetes June 2004; 53(Suppl. 2): A130

HbA1c

40

NovoMix: Once daily when initiated, enabled 42% to achieve target HbA1c (2)

57% (n=53)

20% (n=18)

23% (n=21)

HbA1c ≤6.5%

6.5% < HbA1c <7%

HbA1c ≥7%

Jain et al. Diabetes June 2004;53( Suppl. 2):A130

23% patients reached HbA1c ≤6.5% with NovoMix® 30 OD

42%

41

High safety: 4 yr data

42

NovoMix 30: High safety (4 yr data)- (1)

Hypoglycaemia NovoMix 30 Mixtard 30

At least 1 major episode 4 11

Major Nocturnal 0 6

Minor Nocturnal 5 11

Extension of 3 m European BIAsp 30 study; n=73 with type 2; 4 yr data on safety vs. Mixtard 30

Boehm et al. Diabetologia 2003; 46(Suppl 2):A269

3 findings• Significantly less no. of hypoglycaemic episodes • No major nocturnal episode with NM 30 (6 episodes with

Mixtard 30) • Confirms - with proper use of NovoMix 30, nocturnal

hypoglycaemia can be avoided

43

NovoMix 30: High safety (4 yr data)- (2)

0

2

4

6

8

10

12

Major Episodes Minor episodes

4 years of study

Nu

mb

er

of

No

ctu

rna

l E

pis

od

es

p = 0.02

p = 0.15

5 events

11

events

>50%

0

6 events

No major nocturnal episode with NM 30

Boehm B et al. Diabetologia 2003; 46(Suppl 2):A269

44

• Simple convenient meal-time regimen (3 studies)

– Comparison of pre & post meal (elderly) (Warren or Albery et al.)

– Pre & post meal vs. Mixtard (at or 15 min before meal) (Kapitza et al)

– Mixtard (at or 30 min before meal) (Hermansen et al. 2002)


– vs. Mixtard (Boehm et al 2002-2 slides)

– vs. Lispro Mix & Mixtard (Hermansen et al. 2002)

– vs. NPH (Christiansen et al. 2003)

45

• High safety (3 studies)

– as safe as OADs (Kvapil et al)

– Low risk of nocturnal hypo

• Boehm et al. 2002 (12 wk study)

• Boehm et al. (2 yr study)

• Once-a-day dosing with OADs gives superior control (2 studies)

– Metformin combination (Kilo et al. 2003)

– Glitazone combination (Raz et al. 2003)

• FlexPen – Patient and prescriber acceptance (1 study)

– Lawton et al.

Insulin initiation made safer and simpler

(Premix analogue)

Documents

Insulin initiation made safer and simpler (Premix analogue)