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
• Simple convenient meal-time regimen
– 3 studies
• 24-hour better physiological control
• High safety
• Once-a-day dosing with OADs gives superior control
• FlexPen – Patient and prescriber acceptance
(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
• Simple convenient meal-time regimen
• 24-hour better physiological control
– 3 studies (vs. Mixtard, Lispro Mix, NPH)
• High safety
• Once-a-day dosing with OADs gives superior control
• FlexPen – Patient and prescriber acceptance
(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
• Simple convenient meal-time regimen
• 24-hour better physiological control
• High safety
– 3 studies
• Once-a-day dosing with OADs gives superior control
• FlexPen – Patient and prescriber acceptance
(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
• Simple convenient meal-time regimen
• 24-hour better physiological control
• High safety
• Once-a-day dosing with OADs gives superior control
– 2 studies (with Metformin; with glitazone)
• FlexPen – Patient and prescriber acceptance
(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
• 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
– 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
Raskin et al. Diabetes June 2004; 53 (Suppl. 2): A143
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
Raskin et al. Diabetes June 2004; 53 (Suppl. 2): A143
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)
• 24-hour better physiological control
– 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)