1. Insulin initiation made safer and simpler
(Premix analogue)
Insulin initiation made safer and simpler
Can somebody read this out?
Yes, this is our positioning for NovoMix 30

2. Simple convenient meal-time regimen
(Premix analogue)
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
I want someone to read out these 5 benefits of NovoMix 30. Please qualify each benefit with “NovoMix 30 offers…..”
(As the person reads out elaborate on what studies you’ll present. Use superlatives while describing the studies. For example…… what you’ll see here are the best of the scientifc papers. The studies are conducted by the best-known diabetologists in the world. They are conducted according to the best study designs. They are published in the best of the diabetes journals. ….. and it is all about the best of the insulins, NovoMix 30 to be sold by the sales team of the most admired company in India)

3. Simple convenient meal-time regimen 3 studies
(Premix analogue)
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
Here we go.
First benefit.

4. NovoMix ® 30 can be given pre- or post-meal (1)
(Premix analogue)
Study 1
12-wk, crossover, N=92 (elderly) T2DM 20 40 60 80
100
120
140
160
180
200
Before
breakfast
dinner
2 hrs after
Blood glucose levels (mg/dl)
n = 91
p = NS in all cases
Preprandial dosing (NovoMix® 30, bid)
Postprandial dosing (NovoMix® 30, bid)
Similar BG, given pre- or post meal
Blood glucose levels (mg/dl):
Preprandial dosing Postprandial dosing
(NovoMix® 30, bid) (NovoMix® 30, bid)
Before Breakfast 139 ± ± 55
Dinner 143 ± ± 65
2 hrs after Breakfast 159 ± ± 61
Dinner 143 ± ± 59
Plasma glucose profiles during test meals were also similar:
AUC 0-240min ± vs ± mg/dL/min-1
There was no difference in the number of hypoglycaemic episodes for either treatment group (47 vs 55 episodes during pre- vs. postprandial treatment periods, respectively; p=ns)
Warren et al. Diabetes Res Clin Pract Oct;66(1):23- 9

5. NovoMix ® 30 can be given pre- or post-meal (2)
Study 2
Open-label, crossover trial, N=31, T2DM
Human Mixtard® 30(t = –15 min) 6
Human Mixtard® 30(t = 0 min)
NovoMix® 30(t = 0 min) 4
NovoMix® 30( t= +15 min) 2
Blood glucose (mmol/l)
Postprandial dosing
AUC and glucose Cmax analysis showed no difference NovoMix® 30 (t=+15min) compared with the two Human Mixtard treatments
No major hypoglycaemic episodes were recorded during the trial
Incidence of minor hypo’s was comparable between the four treatment groups
No safety concerns were raised during the trial –2 –4 60
120
180
240
300
Time (min)
Kapitza et al. Diabetic Medicine 2004; 21:500–1

6. PPG control better than Human Mixtard ® 30 with- or before meal
(Premix analogue)
Study 3
Randomized, crossover, 3-arm, single dose comparison with Human Mixtard ® 30, T1DM , N=50
p <
p = 0.013
3000
Human Mixtard® 30
2800
23% 9%
NovoMix® 30
2600
Blood glucose excursion 4 h after injection (mmol.min.l-1)
2400
2200
Compared with Human Mixtard injected at t = 0, NovoMix® 30 reduced the blood glucose excursion by 23% (p < ). When Human Mixtard was injected 30 minutes before the meal, the reduction was of 9% in favour of NovoMix 30 (p=0.013).
2000
t = 0
t = 0
t = –30
Injection time in relation to meal
Hermansen et al. Metabolism 2002;51(7):896–900

7. NovoMix® 30 offers simple convenient meal-time regimen – why?
(Premix analogue)
No waiting period after injection
Can be taken with or after meal
No overflow hypo
This is a summary slide for 1st benefit.

8. Simple convenient meal-time regimen 
(Premix analogue)
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
Follow same style as for 1st benefit

9. 24h improved postprandial glucose after 3 months
(Premix analogue)
12-wk, open-label comparison of NovoMix® 30 bd Vs Mixtard® 30 bd
N= 294, T1 and T2 DM
NovoMix® 30 *
p < 0.05 12 *
Human Mixtard® 30
Study 1 * 10 * * 8
Blood glucose (mmol/l)
European
BIAsp 30
study group 6
Blood glucose concentration was significantly lower after breakfast and dinner, before lunch and at bedtime in the NovoMix® 30 group.
Analysis of 8-point blood glucose profiles revealed significantly lower blood glucose concentrations after breakfast and dinner, before lunch and at bedtime in the NovoMix® 30 group.
At 12 weeks, values were approximately 1% lower in the NovoMix® group after breakfast and dinner (10.4 versus 11.4 mmol/l in NovoMix® 30 and Human Mixtard 30 groups respectively after breakfast, and 9.22 versus 10.2 mmol/l after dinner; p < 0.05 between groups for breakfast and p < 0.02 for dinner).
Before lunch, blood glucose concentrations of 6.64 mmol/l in the NovoMix® 30 group compared favourably with 7.57 mmol/l in the Human Mixtard 30 group (p < 0.02), while at bedtime, concentrations of 8.22 versus 9.10 mmol/l in the NovoMix® 30 and Human Mixtard 30 groups, respectively, again favoured NovoMix® 30 (p < 0.05).
At other time points, between-treatment differences did not reach statistical significance. Importantly, mean prandial glucose concentration was significantly lower in the NovoMix® 30 group after 12 weeks (1.66 versus 2.34 mmol/l in NovoMix® 30 and Human Mixtard 30 groups, respectively; p < 0.02).
Pre-
Post-
Pre-
Post-
Pre-
Post-
Bedtime
0200 h
Breakfast
Lunch
Dinner
Boehm et al. Diabet Med 2002;19(5):393–9

10. NovoMix® 30 produces significantly lower prandial glucose increment than H. Mixtard® 30
(Premix analogue)
0.5 1
1.5 2
2.5 3
p < 0.02 between treatment groups
Study 1
30%
2.34 mM
(mmol/l)
Mean prandial glucose increment
1.66 mM
European
BIAsp 30
study group
At 12 weeks, mean prandial glucose excursion was significantly less (p < 0.02) in the NovoMix 30 group compared with the Human Mixtard 30 group.
Postprandial glycaemic control was significantly better with NovoMix® 30 when analysed on the basis of mean prandial blood glucose increment - mean increment (post-meal minus pre-meal blood glucose) over the three meals including lunch, when no insulin was given.
After 12 weeks, mean prandial glucose increment was 1.66 ± 0.20 mmol/l in the NovoMix® 30 group versus 2.34 ± 0.19 mmol/l for Human Mixtard 30 (p < 0.02).
After three months treatment, levels of HbA1c did not differ between the two treatment groups.
Only subjects who had a complete set of values for each of the 8-point blood glucose time points were included in the analysis.
NovoMix® 30
Human Mixtard® 30
(n = 128)
(n = 141)
Boehm et al. Diabet Med 2002;19(5):393–399

11. Blood glucose excursion
NovoMix® 30 produces significantly lower prandial glucose increment than Lispro Mix
Randomized, crossover, 3-arm, single dose comparison with Lispro Mix and Human Mixtard® , T2DM , N=45
p < 0.001
Study 2 21
–17%
p < 0.05
(mmol/l h) 20
–10% 19
0– 5h 18 17 16
In this randomised, cross-over single-dose trial 61 type 2 diabetic patients were exposed on 3 separate study days to the following treatments in random order:
NovoMix 30, Humalog Mix 25, and Human Mixtard 30, the latter injected 15 minutes before a standard breakfast (0.4 U/kg for all three insulins). No intermediate or long-acting insulin or OHAs were allowed for the 24 hours preceding the trial days. Mean pre-test FPG levels were similar for all 3 groups ( mmol/L).
The PPG excursion over 5 hours was reduced for NovoMix 30 by 10% compared with Mix25, and by 17% compared with Human Mixtard 30.
EXC0-5(glu) (mmol/l h) for the different treatment groups were: Humalog Mix 25 – NovoMix 30 – Human Mixtard 30 – 20.1
Blood glucose excursion 15 14 13
Humalog® Mix 25TM
NovoMix® 30
Human Mixtard® 30
Hermansen K et al. Diabetes Care 2002;25:883–8

12. Greater HbA1c reduction with NovoMix® 30 vs. NPH
(Premix analogue)
16-wk, double-blind, parallel comparison of NovoMix® 30 bd Vs NPH bd
N= 403, T2 DM
NovoMix® 30
NPH
Study 3
0.0
-0.2
-0.4
Change in HbA1c (%)
Subjects who had been taking NPH insulin monotherapy before the trial achieved significantly greater reductions in HbA1c when switched to NovoMix® 30 twice-daily compared to those who added another NPH injection (p < 0.005).
As expected, subjects who were receiving NPH monotherapy (once- or twice-daily) or who were insulin-naïve prior to the study responded more favourably to both NovoMix® 30 and NPH insulin than those who had been taking combination therapy since they did not discontinue any component of treatment before starting on trial medication.
Total population: HbA1c concentration decreased by > 0.6 % (p < versus baseline), in parallel, in both groups; metabolic control continued to improve throughout the trial without reaching a stable level
-0.6
-0.8
p = 0.03
-1.0
Christiansen et al. Diab Obes Met. 2003; 5(6)

13. NovoMix® 30 offers 24-hour better physiological control - Why?
(Premix analogue)
Significantly lower PG increment than human Mixtard®
Significantly reduced HbA1c levels
Summary of benefit 2.

14. Simple convenient meal-time regimen 
(Premix analogue)
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
Follow same style as before throughout

15. Hypo profile as safe as OADs
(Premix analogue)
16-wk, open-label comparison of NovoMix® 30, NM+Met, Met+SU
N=329
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
No other safety concerns were raised
Study 1
Kvapil M et al. Diabetes 2002;51(Suppl 2):A104

16. Low risk of nocturnal hypoglycemia (1)
(Premix analogue)
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)
50% relative
risk reduction
Study 2 45 40 35 30
hypoglycaemic episodes
Number of 42
events 25
European
BIAsp 30
study group 20
Subjects in the NovoMix® 30 group experienced nearly half as many major hypoglycaemic episodes as those in the Human Mixtard 30 group, as well as a trend towards reduced nocturnal hypoglycaemia. 15 20
events 10 5
NovoMix® 30
Human Mixtard® 30
(n = 138)
(n = 153)
Boehm B et al. Diabet Med 2002;19(5):393–399

17. Low risk of nocturnal hypoglycemia (2)
(Premix analogue)
On correct usage, major hypo can be avoided with NovoMix® 30 2 4 6 8 10 12
1st year
2nd year
Year of study
Patients with at least one major
episode (%)
p = NS
p = 0.04
Study 3
NovoMix® 30
Human Mixtard® 30
10%
2-year extension of
European trial
Only T2DM
N=125 8% 5%
This was the continuation of the 3-month study shown before. All analyses shown from this study correspond to the type 2 subgroup (n=125). 95 patients (76%) completed the two year treatment period.
The proportion of patients experiencing major hypoglycemia was similar during the first year (NovoMix 30, 5%; Human Mixtard, 8%; NS) but significantly lower with NovoMix 30 than with Human Mixtard during the second (BIAsp, 0%; Human Mixtard, 10%; P = 0.04).
Minor episodes were also fewer in the NovoMix 30 group, especially in the second year
First treatment year: 265 NovoMix in Human Mixtard 30
Second year: 133 NovoMix * Human Mixtad
*p < 0.05 0%
Boehm et al. Diabetologia 2001; 44 (Suppl 1): A210.

18. NovoMix® 30 offers High safety – Why?
(Premix analogue)
Hypo profile as safe as OADs
Reduced risk of between-meal hypo
Low risk of nocturnal hypo

19. Simple convenient meal-time regimen 
(Premix analogue)
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

20. Metformin combination
(Premix analogue)
US study, 25 centres, N=131, T2 DM, 12 wk
3-arm, open-label comparison of Metformin plus once-daily NM, Mixtard, NPH
Study 1
Insulin (+metformin)
Change in HbA1c
from baseline (%)
NovoMix® 30
NPH
Human Mixtard ® 30 -3
-2.5 -2
-1.5 -1
-0.5
The total population was divided into sub-groups according to the fasting plasma glucose level (mmol/l). Patients in the 5-8 mg/dl sub-group who were treated with NovoMix 30 had a significantly larger reduction in HbA1c compared with the other two treatment groups (p < vs NPH + met and Human Mixtard 30 + met).
Patient numbers:
NovoMix® 30 group – n = 12
NPH group – n = 23
Human Mixtard 30 group – n = 19
NovoMix® 30 better glycemic control than Human Mixtard® 30
Kilo C et al. J Diabetes Compl 2003; 17:

21. Glitazone combination
(Premix analogue)
N=246, T2 DM OAD failure, 18 wk
3-arm, open-label comparison of NM+Pio, NM alone, SU+Pio
11.0
NovoMix® 30
Study 2
10.5
NovoMix® 30 + pioglitazone
Glibenclamide + pioglitazone
10.0
9.5
HbA1c (%) * *
9.0
8.5
8.0
Replace SU/SU+combn failures with NovoMix® 30+Pio in T2DM
7.5
*p < 0.01
7.0
Screening
Visit 6
End of Trial
Raz I et al. Diabetologia 2003;46(Suppl 2):A8

22. NovoMix® 30 offers once-a-day dosing with OADs and gives superior control – Why?
(Premix analogue)
NovoMix® 30 better glycemic control than Human Mixtard® 30 when combined with OADs
Replace SU/SU+combn failures with NovoMix® 30+Pio in T2DM

23. Simple convenient meal-time regimen 
(Premix analogue)
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

24. Patient and prescriber acceptance (1)
(Premix analogue)
N=102
82% of healthcare professionals preferred FlexPen® compared to two other prefilled pens2
Study 1 %
p<0.01 vs. Lilly pen and Aventis pen
82%
14% 3%
FlexPen®
Lilly pen
Aventis prefilled pen
Lawton et al. Diabetes 2001; 50 (suppl 2): A440

25. How can you say that NovoMix® 30 FlexPen enjoys patient and prescriber acceptance?
(Premix analogue)
Studies have shown that > 80% healthcare professionals preferred NovoMix FlexPen

26. Patient profile for NovoMix® 30
(Premix analogue)
Patient profile for NovoMix® 30

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
This is a summary slide stating the obvious.
Clearly we have the ideal tool for safer and simpler early insulin initation in NovoMix 30.
Having built our case for NovoMix 30, let us move on to the details of each of the specific benefits of NovoMix 30.
(Move on to NovoMix 30 slide set)

28. How to use NovoMix® 30? Initiation of NovoMix® 30: 0.2 U/kg/24 h
(Premix analogue)
Initiation of NovoMix® 30:
0.2 U/kg/24 h
Split 2/3 morning, 1/3 evening
Keep OAD dose unchanged
Switching from Human Mixtard 30 or NPH: Dose 1:1

29. NovoMix 30: Kinetics Human Mixtard ® 30 within 30 minutes 2-8 hours
Onset of action
Peak action
Duration of action
We included this because traditionally we have provided such tables with all our insulins. It was missed out in the medical backgrounders we supplied.

30. NovoMix 30 vs. Glargine : New data

31. NovoMix 30 vs. Insulin Glargine (1)
NM30 provides both basal & prandial control (Glargine provides only basal control- controlling PPG is important)
NM 30 - mitogenicity similar to HI; Glargine – 8-fold increased mitogenicity
Retinopathy seen in some patients with type 2 diabetes in studies of 1 year or shorter
Berger M. Lancet 2000;356:2013-4
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
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
Raskin et al. Diabetes June 2004; 53 (Suppl. 2): A143

33. NovoMix 30 vs. Insulin Glargine (3)
NovoMix 30 is superior to Insulin Glargine
Better overall control - lower HbA1c
Better PPG control
More patients achieved target HbA1C of ≤ 6.5% or <7%

34. NovoMix 30 vs. insulin Glargine (4) Better PPG control than Glargine
2 am
Bedtime
Lunch +90
Before lunch
Before dinner
Dinner +90
Breakfast +90
Before breakfast
Raskin et al. Diabetes June 2004; 53 (Suppl. 2): A143

35. NovoMix 30 Vs. Insulin Glargine (5)
More patients achieved target A1C with NM30
p=0.0002
66%
p=0.0356
42%
40%
Patients reaching target
at week 28 (%)
28%
HbA1c target
Raskin et al. Diabetes June 2004; 53 (Suppl. 2): A143

36. NovoMix 30 vs. Insulin Glargine (6) Luzio et al.
Compared PK & PD of NM 30 vs. Glargine
28% greater pl. insulin (AUC) % greater glucose-lowering effect
400
NovoMix® 30
PI AUC0-24h; p<0.01
350
Glargine
300
250
Plasma Insulin (pM)
200
150
100 50 -1 4 9 14 19 24
Time (h)
NovoMix® 30 or glargine
NovoMix® 30
Luzio et al. Diabetes June 2004; 53 (Suppl 2): A136

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%
HbA1c
Baseline
At 16 wks
8.5%
6.1%
2.4%
Jain et al. Diabetes June 2004; 53(Suppl. 2): A130

40. NovoMix: Once daily when initiated, enabled 42% to achieve target HbA1c (2)
23% patients reached HbA1c ≤6.5% with NovoMix® 30 OD
HbA1c ≤6.5%
57% (n=53)
20% (n=18)
23% (n=21)
HbA1c ≥7%
42%
<7% includes both patients who achieved <6.5% & <7%
6.5% < HbA1c <7%
Jain et al. Diabetes June 2004;53( Suppl. 2):A130

41. High safety: 4 yr data

42. NovoMix 30: High safety (4 yr data)- (1)
Extension of 3 m European BIAsp 30 study; n=73 with type 2; 4 yr data on safety vs. Mixtard 30
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
Hypoglycaemia
NovoMix 30
Mixtard 30
At least 1 major episode 4 11
Major Nocturnal 6
Minor Nocturnal 5
Boehm et al. Diabetologia 2003; 46(Suppl 2):A269

43. NovoMix 30: High safety (4 yr data)- (2)
No major nocturnal episode with NM 30 2 4 6 8 10 12
Major Episodes
Minor episodes
4 years of study
Number of Nocturnal Episodes
p = 0.02
p = 0.15
5 events 11
events
>50%
6 events
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 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 (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.

46. Insulin initiation made safer and simpler
(Premix analogue)
Insulin initiation made safer and simpler
(Move on to NovoRapid….)