The dualrelease insulin preparation

1
The dual-release insulin preparation

• Overview of published studies

2
Contents

• NovoMix 30 the dual release insulin
• Contents Slides
• Insulin aspart 3?4
• Dual-release kinetics 5?17
• Postprandial glycaemic control 18?37
• Hypoglycaemia 38?53
• HbA1c control 54?78
• Convenience and flexibility 79?102
• Summary 103
• References 104

3

• Insulin aspart a rapid-acting analogue

4
Insulin aspart preclinical proof-of-concept
Insulin aspart
Human insulin
Adapted from Brange J et al. Nature
1988333679682
5
Dual-release kinetics

6
The dual-release insulin concept BHI 30
7
The dual-release insulin concept
8
Benefits of premix analogues

• NovoMix 30 provides significantly better PPG
  control than BHI 30 and insulin glargine
• 50 more people reach recommended HbA1c target
  with NovoMix 30 than insulin glargine
• NovoMix 30 is a convenient way to start insulin,
  with a simple dosing guideline and the
  easy-to-use FlexPen

9
NovoMix 30PK/PD studies in healthy volunteers

• Comparison
• PK and PD profiles of NovoMix 30 vs. BHI 30
• Design
• Randomised, double-blind, two-way, single dose
  crossover1
• Randomised, double-blind, single dose crossover,
  euglycaemic clamp2

1. Jacobsen L et al. Eur J Clin Pharm
200056399403 2. Weyer C et al. Diabetes Care
19971016121614
10
Proof of concept rapid absorption and higher
peak concentration
Jacobsen L et al. Eur J Clin Pharm 200056399403
11
Proof of conceptfaster onset and more effective
Weyer C et al. Diabetes Care 19971016121614
12
PK/PD conclusions NovoMix 30 vs. BHI 30

• Faster absorption1,2
• Higher peak concentrations1,2
• More rapid and pronounced glucose-lowering
  effect1,2
• Similar duration of action of basal component1,2
• Faster onset and greater glucose-lowering effect
  of insulin aspart are retained in dual-release
  NovoMix 30

1. Jacobsen L et al. Eur J Clin Pharm
200056399403 2. Weyer C et al. Diabetes Care
19971016121614
13
PK and PD of NovoMix 30 and glargine in a
euglycaemic clamp
Clamp 1 Clamp 2
NovoMix 30
NovoMix 30
Glargine
Glargine

• Total 24 hour dose of insulin 0.5 U/kg -
  NovoMix 30 (0.25 U/kg) injected at 08.00h and
  20.00h - Glargine (0.5 U/kg) injected at
  08.00h
• All 12 type 2 patients were male age 58.3 (8.3)
  years, BMI 31.7 (3.4) kg/m2, HbA1c 7.3 (0.9)
  mean (SD)

Luzio S et al. Diabetes 200453(Suppl. 2)A136
14
PK 28 greater AUC with NovoMix 30 than glargine
400
NovoMix 30
PI AUC0-24h plt0.01
Glargine
350
300
250
Plasma insulin (pM)
200
150
100
50
0
-1
4
9
14
19
24
Time (h)
NovoMix 30
NovoMix 30 or glargine
Luzio S et al. Diabetes 200453(Suppl. 2)A136
15
Endogenous insulin suppression with NovoMix 30,
but not with glargine
NovoMix 30
1.40
Glargine
1.20
1.00
Plasma C-Peptide (nM)
0.80
0.60
0.40
C-peptide AUC0-24h p0.015
0.20
0.00
-1
4
9
14
19
24
Time (h)
NovoMix 30
NovoMix 30 or glargine
Luzio S et al. Diabetes 200453(Suppl. 2)A136
16
Insulin action NovoMix 30 has a 34 greater
glucose-lowering effect
NovoMix 30
3.5
Glargine
GIR AUC0-24h plt0.01
3.0
2.5
2.0
GIR (mg/kg/min)
1.5
1.0
0.5
0.0
-1
4
9
14
19
24
Time (h)
NovoMix 30
NovoMix 30 or glargine
Luzio S et al. Diabetes 200453(Suppl. 2)A136
17
Greater glucose-lowering effect with NovoMix 30

• Although equivalent doses of NovoMix 30 and
• glargine were administered
• 28 greater plasma insulin (AUC) with NovoMix
  30 than glargine
• 34 greater glucose-lowering effect with NovoMix
  30 than glargine
• Endogenous insulin production suppressed by 14
  with NovoMix 30 but not with glargine

Luzio S et al. Diabetes 200453(Suppl. 2)A136
18

• Improved postprandial glycaemic control

Return to contents slide
19
Twice-daily NovoMix 30 in patients with type 2
diabetes
Screening visit (n 13)
Follow-up
NovoMix 30
NovoMix 30
BHI 30
BHI 30
3 to 7 days
3 to 14 days
4
2
0
Weeks
McSorley PT et al. Clin Ther 200224(4)530539
20
NovoMix 30 is rapidly absorbed
NovoMix 30
Biphasic human insulin
n 13
p lt 0.05 in favour of NovoMix 30 for mean serum
insulin level and insulin Cmax after dinner and
breakfast
Time
McSorley PT et al. Clin Ther 200224(4)530539
21
Improved postprandial glucose control with
NovoMix 30
p lt 0.05 in favour of NovoMix 30 for lower PPG
levels after dinner and breakfast
McSorley PT et al. Clin Ther 200224(4)530539
22
NovoMix 30 is well tolerated

• Both insulins were well tolerated
• Both insulins had comparable adverse-event
  profiles
• No major hypoglycaemic episodes or serious
  adverse events were reported
• No other safety concerns

McSorley PT et al. Clin Ther 200224(4)530539
23
NovoMix 30 twice daily improves postprandial
glucose control

• Compared with BHI 30, NovoMix 30 given
  immediately before a meal (twice daily) in
  patients with type 2 diabetes resulted in
• Significantly faster absorption
• Significantly higher peak concentrations 2 hours
  after injection
• Smaller postprandial glucose excursions
• No safety concerns

McSorley PT et al. Clin Ther 200224(4)530539
24
Comparison of NovoMix 30, Humalog Mix25TM and
BHI 30

• Objective To compare the postprandial blood
  glucose excursion between treatment groups
• Design Randomised, open-labelled, three-period
  crossover trial
• Method Single dose meal test, NovoMix 30 and
  Humalog Mix25TM immediately before meal, BHI 30
  15 min before meal
• Population 45 patients with type 2 diabetes
• Primary test EXC (glucose 05h)

Hermansen K et al. Diabetes Care 200225883888
25
Reduced glucose excursions vs. Humalog Mix25TM
and BHI 30
Hermansen K et al. Diabetes Care 200225883888
26
Improved postprandial control vs. Humalog
Mix25TM and BHI 30
a NovoMix 30 significantly less than Humalog
Mix25TM (p lt 0.05) b NovoMix 30 significantly
less than BHI (p lt 0.001) c NovoMix 30
significantly earlier than BHI (p lt 0.05) d
NovoMix 30 significantly earlier than Humalog
Mix25TM (p lt 0.01)
Hermansen K et al. Diabetes Care 200225883888
27
Larger and more rapid increasein serum insulin
with NovoMix 30
a Values for NovoMix 30 are significantly
different from BHI 30 (p lt 0.001)
Hermansen K et al. Diabetes Care 200225883888
28
Improved postprandial glucose vs. BHI 30 and
Humalog Mix25TM

• Superior postprandial glucose control to BHI 30
  and Humalog Mix25TM in type 2 patients
• Higher maximum serum insulin than with BHI and
  Humalog Mix25TM
• Well tolerated with no serious adverse events
  occurring related to treatment

Hermansen K et al. Diabetes Care 200225883888
29
Comparison of efficacy and safety of NovoMix 30
vs. BHI 30 study design
Insulin-using patients with type 1 and type 2
diabetes (n 294)
Boehm B et al. Diabet Med 200219(5)393399
30
Improved postprandial glucose after 3 months

Boehm B et al. Diabet Med 200219(5)393399
31
Significantly lower prandial glucose increment
with NovoMix 30
Boehm B et al. Diabet Med 200219(5)393399
32
Improved postprandial control with NovoMix 30

• Superior postprandial glycaemic control achieved
  compared with BHI 30
• No increased risk of hypoglycaemia with NovoMix
  30
• Trend for reduction in nocturnal hypoglycaemic
  episodes with NovoMix 30

Boehm B et al. Diabet Med 200219(5)393399
33
NovoMix 30 vs. NPH in type 2 patients
Christiansen JS et al. Diabetes Obes Metab
20035(6)445-452
34
NovoMix 30 vs. NPH lower prandial glucose
increment
Breakfast Lunch Dinner

Christiansen JS et al. Diabetes Obes Metab
20035(6)445-452
35
Greater HbA1c reduction with NovoMix 30 vs. NPH
Christiansen JS et al. Diabetes Obes Metab
20035(6)445-452
36
NovoMix 30 offers better glycaemic control than
NPH

• Mean prandial glucose increment lower in NovoMix
  30 group (p lt 0.0001)
• Patients receiving NPH monotherapy benefit from
  switching to NovoMix 30 (bid)

Christiansen JS et al. Diabetes Obes Metab
20035(6)445-452
37
Superior postprandial control

• Higher plasma insulin levels with NovoMix 30 vs.
  BHI 30
• Improved postprandial control vs. BHI 30
• Superior postprandial control vs. Humalog
  Mix25TM
• Lower postprandial increment and HbA1c vs. NPH
• No safety concerns

38
Superior hypoglycaemia profile
39
REACH Randomised Evaluation of Aspart mix 30 on
Control and Hypoglycaemia
Randomisation start of double-blindtreatment
(HbA1c 6.58.5)

• Patient inclusion
• Type 2 diabetes
• HbA1c lt 9.5
• Already using insulin

Cross-over
BHI 30
BHI 30
Existing insulin regimen
NovoMix 30
NovoMix 30
Screen and run-in (8 weeks)
Period 2 (16 weeks)
Period 1 (16 weeks)
CBGM
insulin dose titrated to achieve pre-breakfast
and pre-dinner blood glucose of 57 mmol/l CBGM,
Continuous Blood Glucose Monitoring over a
72-hour period BHI 30, Biphasic Human Insulin
30 Injected just before breakfast and just
before the evening meal
40
Objectives of REACH

• Primary objective
• Frequency of hypoglycaemic episodes (lt 3.5
  mmol/l) recorded using continuous blood glucose
  monitoring (MiniMed)
• Secondary objectives
• Nocturnal hypoglycaemia
• Major hypoglycaemic episodes
• Glycaemic control (HbA1c)
• Treatment satisfaction

McNally P et al. Diabetologia 200447(Suppl.
1)A327
41
Run-in period glucose readings below 3.5 mmol/l
occur fairly frequently during insulin treatment

• 72 of participants experienced at least one
  blood glucose reading lt 3.5 mmol/l

McDougall A et al. Diabetologia 200447(Suppl.
1)A275
42
REACH significantly fewer nocturnal glucose
readings below 3.5 mmol/l with NovoMix 30 than
with BHI 30
McNally P et al. Diabetologia 200447(Suppl.
1)A327. Data on file, Novo Nordisk.
43
REACH results summary

• Incidence of nocturnal hypoglycaemia
  significantly lower with NovoMix 30 than with
  BHI 30
• Fewer major hypoglycaemic episodes with NovoMix
  30
• No difference in overall incidence of
  hypoglycaemia between NovoMix 30 and BHI 30
• No difference in HbA1c between NovoMix 30 and
  BHI 30 over duration of study

McNally P et al. Diabetologia 200447(Suppl.
1)A327 McDougall A et al. Diabetologia
200447(Suppl. 1)A275
44
Comparison of efficacy and safety of NovoMix 30
vs. BHI 30 study design
Insulin-using patients withtype 1 and type 2
diabetes (n 294)
Boehm B et al. Diabet Med 200219(5)393399
45
Improved postprandial glucose after 3 months

Boehm B et al. Diabet Med 200219(5)393399
46
Significantly lower prandial glucose increment
with NovoMix 30
Boehm B et al. Diabet Med 200219(5)393399
47
Reduced major hypoglycaemia after 3 months
Boehm B et al. Diabet Med 200219(5)393399
48
Trend towards reduced minor nocturnal
hypoglycaemic episodes
Boehm B et al. Diabet Med 200219(5)393399
49
Reduced hypoglycaemic profile with NovoMix 30

• Superior postprandial glycaemic control achieved
  compared with BHI 30
• No increased risk of hypoglycaemia with NovoMix
  30
• Trend for reduction in nocturnal hypoglycaemic
  episodes with NovoMix 30

Boehm B et al. Diabet Med 200219(5)393399
50
NovoMix 30 vs. BHI 30 2-year safety in type 2
diabetes
Boehm B et al. Eur J Int Med 200415(8)496-502
51
Reduced major hypoglycaemia after 2 years
NovoMix 30 BHI 30
Boehm B et al. Eur J Int Med 200415(8)496-502
52
Reduced minor hypoglycaemia after 2 years
NovoMix 30 BHI 30
p 0.46
70
60
p 0.22
50
40
Patients with at least one minor episode ()
30
20
10
0
2nd year
1st year
Year of study
Boehm B et al. Eur J Int Med 200415(8)496-502
53
2-year efficacy and tolerability of NovoMix 30
in type 2 diabetes

• Compared with BHI 30, NovoMix 30 is associated
  with
• A reduced risk of major hypoglycaemia
• A similar risk of minor hypoglycaemia
• An equivalent level of efficacy
• More favourable balance between hypoglycaemia and
  hyperglycaemia in insulin-treated type 2 diabetes

Boehm B et al. Eur J Int Med 200415(8)496-502
54
HbA1c control with NovoMix 30
55
INITIATE INITiation of Insulin to reach A1c
TargEt NovoMix 30 (bid) vs glargine (od)
n 233 Type 2 diabetes BMI lt 40 kg/m2Body
weight lt125 kg HbA1C gt 8 on metformin /- TZD
Glargine od (12 U, bedtime) metformin /-
pioglitazone
NovoMix 30, pre-breakfast (6U) and pre-dinner
(6U) metformin /- pioglitazone
4 week run-in Stop insulin secretagogues and
?-glucosidase inhibitors Optimize metformin to
1500 mg/day Switch rosiglitazone for 30 mg
pioglitazone

-4 0 (Weeks) 28
Raskin P et al. Diabetes Care 200528260-5
56
Study endpoints for INITIATE

• Primary Compare HbA1c reduction
• Secondary
• Endpoint HbA1C values including the proportion of
  patients achieving HbA1C lt 7.0 and lt6.5
• 8-point BG profile showing fasting plasma glucose
  and postprandial glucose
• Safety, including number of hypoglycaemic events
  (major, minor and nocturnal) and adverse events
• Treatment satisfaction as determined by the
  Diabetic Treatment Satisfaction Questionnaire
  (DTSQ) and Insulin Treatment Satisfaction
  Questionnaire (ITSQ)
• Insulin dose and weight change

Raskin P et al. Diabetes Care 200528260-5
57
Treat-to-target Initiation and titration

• Starting doses
• NovoMix 30 in FlexPen Glargine in vial
• 12U (6U breakfast, 6U dinner) 12U at bedtime
• If FPG lt180 mg/dl or 10 mmol/l10U (5U 5U for
  NovoMix 30)
• Titration occurred weekly during the first 12
  weeks, then every 2 weeks thereafter
• Titration of dinnertime NovoMix 30 and bedtime
  glargine based on fasting blood glucose (80110
  mg/dl, 4.46.1 mmol/l) over previous 3 days
  breakfast NovoMix 30 titrated based on
  pre-dinner blood glucose over previous 3 days

Raskin P et al. Diabetes Care 200528260-5
58
Treat-to-target with forced titration
Raskin P et al. Diabetes Care 200528260-5
59
Similar baseline demographics between treatment
groups
C Caucasian B Black H Hispanic A Asian O
other. Adverse event withdrawals in the
NovoMix 30 group were unrelated to treatment
stroke, adenocarcinoma, chest pain, and
gastrointestinal bleeding. One patient in the
glargine group withdrew for injection site
stinging with possible relationship to study
drug.
Raskin P et al. Diabetes Care 200528260-5
60
Blood glucose profiles
18
NovoMix 30
Glargine
16
14
Baseline
12


10
Blood glucose (mmol/l)



8
plt0.0001
p0.044
plt0.0001
6
p0.012
Week 28
p0.0002
4
0
Beforebreakfast
Breakfast 90
Before lunch
Lunch 90
Before dinner
Dinner 90
Bedtime
200 AM
Raskin P et al. Diabetes Care 200528260-5
61
Reduction (from baseline) in blood glucose
NovoMix 30
Glargine
Time of measurement
BB
B90
BL
L90
BD
D90
Bed
3am
-60
-80
BG reduction mg/dL
-100
-120
-140
-160
62
Improved control of postprandial glucose with
NovoMix 30
Difference in prandial glucose increment between
treatments (mmol/l)
n.s.
p lt 0.05 p lt 0.01
1
0.66
0.5
0
-0.5
-0.59
-1

-1.17
-1.25
-1.5


-2
-2.5
Total mean prandial glucose increment
Breakfast Lunch Dinner

Raskin P et al. Diabetes Care 200528260-5
63
Greater improvements in HbA1c with NovoMix 30
than glargine
Raskin P et al. Diabetes Care 200528260-5
64
Significantly more patients met HbA1c targets
with NovoMix 30 than glargine
Raskin P et al. Diabetes Care 200528260-5
65
INITIATE Hypoglycaemia

• One major hypoglycaemic episode reported during
  the trial this was in the glargine group
• At least one episode of minor hypoglycaemia
  (BGlt56 mg/dl or 3.1 mmol/l) was experienced in
  43 of NovoMix 30-treated patients and 16 of
  glargine-treated patients
• Similar treatment satisfaction

Raskin P et al. Diabetes Care 200528260-5
66
INITIATE Overall hypoglycaemic events
Minor episodes have confirmed BG lt 56 mg/dl (3.1
mmol/l)

• During the 28-week trial, minor hypoglycemia was
  reported by 43 patients in the NovoMix 30 group
  and 16 patients in the glargine group.

Raskin P et al. Diabetes Care 200528260-5
67
INITIATE Weight gain, insulin dose and treatment
satisfaction

• End of trial parameters NovoMix 30 Glargine
• Total daily insulin dose (U/kg) 0.82 ?0.40 0.55
  ?0.27
• Split of NovoMix 30 dose between meals 49-51
• Weight gain (kg) 5.4 ?4.8 3.5 ?4.5 (p0.0013)
• Weight gain per insulin unit (kg/U) 0.08
  ?0.09 0.08 ?0.09
• Treatment satisfaction (ITSQ) 51.0 ?24.3 50.0
  ?24.2
• (scale 25 175, most positive to most negative)

Raskin P et al. Diabetes Care 200528260-5
68
NovoMix 30 in combination withmetformin
NovoMix 30 bid metformin (n 108)
(n 329)
NovoMix 30 bid (n 107)
Metformin failures
(HbA1c 7.513.0)
glibenclamide metformin (n 114)
16
0
Weeks
Kvapil M et al. Diabetes 200251(Suppl. 2)A104
69
Demographic characteristics (total population)
NovoMix 30 plus metformin intype 2 diabetes
Kvapil M et al. Diabetes 200251(Suppl. 2)A104
70
Improved HbA1c with NovoMix 30 combination in
total population
Kvapil M et al. Diabetes 200251(Suppl. 2)A104
71
Superior glycaemic control with NovoMix 30
metformin in poorly controlled patients (HbA1c gt
9)
Kvapil M et al. Diabetes 200251(Suppl. 2)A104
72
Lower insulin dose when used with metformin
NovoMix 30 met
NovoMix 30
Met SU
0.6
0.4
NovoMix 30 dose (IU/mg/day)
SU dose (mg/day)
0.2
0
0
1
2
3
4
Time (months)
Time (months)
Kvapil M et al. Diabetes 200251(Suppl. 2)A104
73
NovoMix 30 plus metformin is well tolerated

• There were no reports of major hypoglycaemia
  during the trial
• The total number of minor hypoglycaemic episodes
  was similar between groups
• NovoMix 30 met 23
• NovoMix 30 alone 20
• Met SU 28
• No other safety concerns were raised

Kvapil M et al. Diabetes 200251(Suppl. 2)A104
74
Improved glycaemic control with NovoMix 30
combination

• In poorly controlled patients NovoMix 30 plus
  metformin achieved better glycaemic control than
  NovoMix 30 alone or sulphonylurea plus metformin
• The end of trial mean weight was not different
  between the NovoMix 30 plus metformin group and
  SU plus metformin group
• NovoMix 30 plus metformin is well tolerated
• There was no difference in hypoglycaemia between
  the two groups

Kvapil M et al. Diabetes 200251(Suppl. 2)A104
75
Once-daily (dinnertime) NovoMix 30 with metformin
Metformin human insulin NPH od (n 47)
Follow-up
4 0 12
14 Weeks
Kilo C et al. J Diabetes Complications
200317(6)307-13
76
Addition of insulin to metformin improves
glycaemic control
Kilo C et al. J Diabetes Complications
200317(6)307-13
77
Benefits of reaching fastingglycaemic targets
Kilo C et al. J Diabetes Complications
200317(6)307-13
78
No major hypoglycaemic events during the study
Kilo C et al. J Diabetes Complications
200317(6)307-13
79
Convenience and flexibility
80
Patient preference for NovoMix 30 compared with
BHI 30

• Patients with type 2 diabetes received either
  NovoMix 30 or BHI 30 both treatments were
  administered twice daily during the 12-week trial
• Patients continued on their respective treatment
  for 6 months
• An analysis of preference-weighted treatment
  satisfaction (diabetes-specific Quality of Life
  scale combined for type 1 and type 2 diabetes)
  was performed at the 6-month follow-up visit
• Patients receiving NovoMix 30 scored
  significantly higher than BHI 30-treated patients
  (plt0.05)

Home P et al. Diabetes Res Clin Pract
200050(Suppl. 1)S37
81
Postprandial dosing with NovoMix 30
NovoMix 30, 0 min
NovoMix 3015 min BHI 3015 min
BHI 30, 0 min
Visit 1 2 3
4 5 6 (Screening)
(Randomisation) (Follow-up)
Days between visits
521 321 321
321 114
Kapitza C et al. Diabet Med 200421(5)500-501
82
Postprandial dosing efficacy with NovoMix 30
BHI 30(t 15 min)
6
BHI 30(t 0 min)
NovoMix 30(t 0 min)
NovoMix 30(t 15 min)
Kapitza C et al. Diabet Med 200421(5)500-501
83
Postprandial dosing with NovoMix 30
Values are expressed as geometric means a AUC
for NovoMix 30 significantly smaller than both
BHI treatments (p 0.0057 and p 0.0006 for t
15 min and t 0 min, respectively) b Cmax is
smaller for NovoMix 30 (t 0 min) compared with
both BHI treatments, but only significantly
smaller than BHI (t 0 min) (p 0.007)
Kapitza C et al. Diabet Med 200421(5)500-501
84
NovoMix 30 allows flexible dosing

• Superior postprandial blood glucose control
  compared with either of BHI 30 injection regimens
  
• Comparable postprandial blood glucose control
  when injected 15 min after start of meal to BHI
  30 injected 0 or 15 min before meal
• Gives advantage of increased flexibility in
  injection timing
• Opportunity to alter insulin dose according to
  meal size and composition

Kapitza C et al. Diabet Med 200421(5)500-501
85
Postprandial NovoMix 30 dosing in elderly
patients
Warren ML et al. Diabetes Res Clin Pract
200466(1)23-29
86
Blood glucose levels did not differ between
injection times
Warren ML et al. Diabetes Res Clin Pract
200466(1)23-29
87
Postprandial NovoMix 30 is effective in elderly
type 2 patients

• Postprandial NovoMix 30 offers acceptable
  alternative to standard preprandial injections
• No significant difference in hypoglycaemic
  episodes between treatment groups
• Postprandial injections appear to be well
  tolerated

Warren ML et al. Diabetes Res Clin Pract
200466(1)23-29
88
Comparison of NovoMix 30 FlexPen with Humalog
Mix25TM Pen
Niskanen L et al. Clin Ther 200426(4)531-540
89
NovoMix 30 FlexPen is simple to use

• Device-specific, and comparative questionnaires
  assessed patients opinion about attributes of
  the devices
• Features included
• confidence in setting and injecting the correct
  dose
• readability of the dose scale
• confidence in managing daily insulin injections
  using the pen device
• For all 16 device features assessed NovoMix 30
  FlexPen was statistically superior to Humalog
  Mix25 Pen, p lt 0.001

Niskanen L et al. Clin Ther 200426(4)531-540
90
NovoMix 30 FlexPen is preferred over Humalog
Mix25TM Pen
p lt 0.001 compared with Humalog Mix25TM Pen
Overall, which pen device would you prefer to
continue to use after this trial?
Niskanen L et al. Clin Ther 200426(4)531-540
91
Higher patient satisfaction with NovoMix 30
FlexPen

• Patients were more satisfied and experienced
  fewer problems than with the Humalog Mix25TM Pen
• More patients found the NovoMix 30 FlexPen the
  easiest device to use
• More patients (75) would continue to use the
  NovoMix 30 FlexPen while only 14 of Humalog
  Mix25TM Pen users would
• Efficacy and safety of NovoMix 30 and Humalog
  Mix25TM were comparable

Niskanen L et al. Clin Ther 200426(4)531-540
92
Comparison of FlexPen with Humalog Pen
Both pens contained rapid-acting analogues,
however, no insulin was injected during the
testing procedure
Asakura T Seino H. Diabetes Metab 2003294S236
93
FlexPen is more user-friendly than Humalog Pen
FlexPen
Humalog Pen
p lt 0.01 p lt 0.001
Pen feature
Asakura T Seino H. Diabetes Metab 2003294S236
94
More patients prefer FlexPen to Humalog Pen
Asakura T Seino H. Diabetes Metab 2003294S236
95
FlexPen is simple to use

• Patients preferred FlexPen to Humalog Pen for
• Readability of the dosing scale
• Ease of dose setting
• Ease of pressing the release button
• Stability during injection
• Simplicity
• Confirmation of injection
• No difference between the devices regarding grip
  and portability

Asakura T Seino H. Diabetes Metab 2003294S236
96
Comparison of FlexPen vs. vial/syringe
Korytkowski M et al. Clin Ther 200325(11)2836-28
48
97
Patients prefer FlexPen to vial/syringe
6
FlexPen
20
Vial/syringe
Q Overall, which device would you prefer to
continue using?
No difference
Significantly more patients (plt0.05) preferred
to continue using FlexPen vs. vial/syringe
74
Korytkowski M et al. Clin Ther 200325(11)2836-28
48
98
FlexPen is preferred to vial/syringe in a number
of injection parameters
Easier to read dose
Confidence in setting dose
Confidence in injecting correct dose
Injection parameters
More discreet in public
More stable
Easier to handle
Confidence in glycaemic control
Easier to use
0
10
20
30
40
50
60
70
80
90
100
Patients expressing preference ()
Korytkowski M et al. Clin Ther 200325(11)2836-28
48
99
Reduction in HbA1c with NovoMix 30
Korytkowski M et al. Clin Ther 200325(11)2836-28
48
100
FlexPen is preferred to vial/syringe

• Both injection devices demonstrated high
  acceptance by the patients according to the
  Diabetes Treatment Satisfaction Questionnaire
  (DTSQ)
• Efficacy and safety profiles were similar between
  treatment groups
• Given the choice, more patients expressed a
  preference to continue using FlexPen to
  vial/syringe

Korytkowski M et al. Clin Ther 200325(11)2836-28
48
101
Healthcare professionals opinion
82 of healthcare professionals preferred
FlexPen compared with two other prefilled pens
Lawton S et al. Diabetes 200150(Suppl. 2)A440
102
Convenient and flexible dosing with NovoMix 30
FlexPen

• NovoMix 30 offers flexible dosing times while
  maintaining good postprandial glycaemic control
• Patients prefer NovoMix 30 FlexPen to Humalog
  Mix25TM Pen
• Patients with impaired manual dexterity and
  vision prefer FlexPen to Humalog Pen

103
NovoMix 30 - Summary

• NovoMix 30 provides significantly greater PPG
  control than BHI 30 and insulin glargine
• 66 of people on NovoMix 30 can reach HbA1c
  target of 7, compared with only 42 on insulin
  glargine
• NovoMix 30 is a convenient way to start insulin,
  with a simple dosing guideline and the
  easy-to-use FlexPen

104
Publications/abstracts in this slide kit

• Asakura T Seino H. Diabetes Metab 2003294S236
• Boehm B et al. Diabet Med 200219(5)393399
• Boehm B et al. Eur J Int Med 200415(8)496-502
• Boehm B et al. Diabetologia 200346(Suppl.
  2)A269
• Brange J et al. Nature 1988333679682
• Christiansen JS et al. Diabetes Obes Metab
  20035(6)445-452
• Hermansen K et al. Metabolism 200251(7)896900
• Home P et al. Diabetes Res Clin Pract
  200050(Suppl 1)S37
• Jacobsen L et al. Eur J Clin Pharm
  200056399403
• Kapitza C et al. Diabet Med 200421(5)500-501
• Kilo C et al. J Diabetes Complications
  200317(6)307-313

• Korytkowski M et al. Clin Ther 200325(11)2836-2
  848
• Kvapil M et al. Diabetes 200251(Suppl. 2)A104
• Lawton S et al. Diabetes 200150 (Suppl. 2)A440
• Luzio S et al. Diabetes 2004 53(Suppl. 2)A136
• McDougall A et al. Diabetologia 200447(Suppl.
  1)A275
• McNally P et al. Diabetologia 200447(Suppl.
  1)A327
• McSorley PT et al. Clin Ther 200224(4)530539
• Mortensen H et al. Diabetes Metab 2003294S227
• Niskanen et al. Clin Ther 200426(4)531-540
• Raskin P et al. Diabetes Care 200528260-5.
• Warren ML et al. Diabetes Res Clin Pract
  200466(1)23-29
• Weyer C et al. Diabetes Care 19972016121614