The dual release insulin preparation
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The dual-release insulin preparation. Overview of published studies. Contents. NovoMix ® 30 – the dual release insulin ContentsSlides Insulin aspart 3  4 Dual-release kinetics 5  12 Postprandial glycaemic control 13 36 Hypoglycaemia 37 50

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The dual release insulin preparation

The dual-release insulin preparation

Overview of published studies


Contents

Contents

NovoMix® 30 –the dual release insulin

ContentsSlides

Insulin aspart34

Dual-release kinetics512

Postprandial glycaemic control1336

Hypoglycaemia3750

Combination with oral medications5176

Convenience & flexibility7794

Use in adolescents9596


The dual release insulin preparation

Return to contents slide

Insulin aspart – a rapid acting analogue


Insulin aspart preclinical proof of concept

Insulin aspart: preclinical proof-of-concept

4.5

Insulin aspart

IRI (10-10 M)

3.0

Human insulin

1.5

0

5

4

Plasma glucose (mM)

3

Injection

2

0

1

4

2

3

5 hours

Adapted from Brange J et al. Nature 1988;333:679–682


The dual release insulin preparation

Return to contents slide

Dual-release kinetics


The dual release insulin concept bhi 30

  • Physiological insulin profile:

    • basal component

    • meal-related peaks

Physiological insulin profile

BHI 30

Soluble human insulin

NPH

  • Soluble insulin fails to match normal insulin peak

  • Intermediate-acting insulin provides basal insulin replacement but…

  • …together these fail to re-create the physiological insulin profile

The dual-release insulin concept – BHI 30


The dual release insulin concept

  • Physiological insulin profile:

    • basal component

    • meal-related peaks

  • Analogue premixes such as NovoMix® 30 replace both meal-related and basal insulin

The dual-release insulin concept

Physiological insulin profile

Soluble insulin aspart

Protamine crystallised insulin aspart

  • Rapid-acting insulin analogues together with a basal insulin provide physiological insulin replacement

NovoMix® 30


Benefits of dual release insulin replacement

Benefits of dual-release insulin replacement

  • Mimics physiological insulin release

    • Early release of rapid-acting insulin targets postprandial glucose

    • Delayed release of intermediate-acting insulin fulfils basal insulin requirement

  • Reduces hypoglycaemic risk

    • < Conventional premix

  • Improves HbA1c in combination with oral medications

  • Simplifies dosing

    • Option of postprandial dosing


Novomix 30 pk pd studies in healthy volunteers

NovoMix® 30:PK/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, crossover single dose euglycaemic clamp2

1. Jacobsen L et al. Eur J Clin Pharm 2000;56:399–403 2. Weyer C et al. Diabetes Care 1997;10:1612–1614


Proof of concept rapid absorption and higher peak concentration

NovoMix® 30

BHI 30

Proof of concept: rapid absorption and higher peak concentration

25

***

20

***p < 0.0001n = 24

15

Serum insulin (mU/l)

10

5

0

8:00

11:00

14:00

17:00

20:00

23:00

2:00

5:00

8:00

Time of day

Jacobsen L et al. Eur J Clin Pharm 2000;56:399–403


Proof of concept faster onset and more effective

Proof of concept:faster onset and more effective

n = 24, dose = 0.3 U/kg

12

NovoMix®30

10

BHI 30 (Actraphane)

8

Glucose infusion rate (mg/kg/min)

6

4

2

0

0

240

480

720

960

1200

1400

Time (min)

Weyer C et al. Diabetes Care 1997;10:1612–1614


Pk pd conclusions novomix 30 vs bhi 30

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 2000;56:399–403 2. Weyer C et al. Diabetes Care 1997;10:1612–1614


The dual release insulin preparation

Return to contents slide

Improved postprandial glycaemic control


Twice daily novomix 30 in patients with type 2 diabetes

Screening visit (n = 13)

NovoMix®30

NovoMix® 30

BHI 30

BHI 30

Twice-daily NovoMix® 30 in patients with type 2 diabetes

Follow-up

+3 to 7 days

–3 to14 days

4

0

2

Weeks

McSorley PT et al. Clin Ther 2002;24(4):530–539


Novomix 30 is rapidly absorbed

NovoMix® 30 is rapidly absorbed

*

*

NovoMix®30

120

Biphasic human insulin

100

n = 13

* p < 0.05 in favour of NovoMix® 30 for mean serum insulin level and insulin Cmax after dinner and breakfast

80

Total serum insulin (mU/l)

60

40

20

0

18:00

22:00

08:00

13:00

18:00

Time

McSorley PT et al. Clin Ther 2002;24(4):530–539


Improved postprandial glucose control with novomix 30

Improved postprandial glucose control with NovoMix® 30

NovoMix®30

Biphasic human insulin

20

*

*

n = 13

15

Blood glucose (mmol/l)

10

5

* p < 0.05 in favour of NovoMix® 30 for lower PPG levels after dinner and breakfast

0

18:00

22:00

08:00

13:00

18:00

Time

McSorley PT et al. Clin Ther 2002;24(4):530–539


Novomix 30 is well tolerated

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 2002;24(4):530–539


Novomix 30 twice daily improves postprandial glucose control

NovoMix® 30 twice daily improves postprandial glucose control

Compared with BHI 30, NovoMix® 30 given immediately before a meal (twice daily) in type 2 diabetic patients 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 2002;24(4):530–539


Type 1 diabetes single dose crossover

3–21 days

5–21 days

5–21 days

Type 1 diabetes: single dose crossover

NovoMix® 30 at meal

Screening

Follow-up

BHI 30 at meal

(n = 50)

BHI 30 at –30 minutes

Study day 1 Study day 2 Study day 3

7–14 days

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


The dual release insulin preparation

*

Max glucose concn

15% lower at t = 0

* p < 0.001n = 50

*

23% lower glucose

exposure

than BHI at t = 0

*

Max glucose concn

20 min earlier

Reduced glucose exposure in

type 1 patients after a meal

NovoMix® 30 (t = 0)

BHI 30 (t = 0)

20

BHI 30 (t = –30)

15

Blood glucose (mmol/l)

10

5

0

–30

30

90

120

150

180

210

240

0

60

Nominal time (min)

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


Reduced glucose excursion irrespective of timing of bhi 30 injection

p < 0.0001

p = 0.013

23%

9%

Reduced glucose excursion irrespective of timing of BHI 30 injection

3000

BHI 30

2800

NovoMix® 30

2600

Blood glucose excursion 4 h after injection (mmol.min.l-1)

2400

2200

2000

0

t = 0

t = –30

t = 0

Injection time in relation to meal

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


Novomix 30 is more effective than bhi 30

NovoMix® 30 is more effective than BHI 30

  • Superior efficacy in controlling postprandial glucose levels

  • Higher reduction in blood glucose concentrations when injected immediately before meals

  • Significantly larger insulin concentrations achieved regardless of the time of BHI 30 administration

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


Comparison of novomix 30 humalog mix25 tm and bhi 30

Comparison of NovoMix® 30, Humalog® Mix25TM and BHI 30

NovoMix® 30 at meal

  • ObjectiveTo compare the postprandial blood glucose excursion between treatment groups

  • DesignRandomised, 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 type 2 patients

  • Primary test EXC (glucose 0–5h)

Humalog® Mix25TM at meal

(n = 45)

BHI 30 at –15 min

Hermansen K et al. Diabetes Care 2002;25:883–888


Reduced glucose excursions vs humalog mix25 tm and bhi 30

p < 0.001

p < 0.05

Reduced glucose excursions vs. Humalog®Mix25TM and BHI 30

21

–17%

(mmol/l h)

20

–10%

19

0– 5h

18

17

16

Blood glucose excursion

15

14

13

0

Humalog® Mix 25TM

NovoMix® 30

BHI 30

Hermansen K et al. Diabetes Care 2002;25:883–888


Improved postprandial control vs humalog mix25 tm and bhi 30

Improved postprandial control vs. Humalog®Mix25TM and BHI 30

a NovoMix® 30 significantly less than Humalog® Mix25TM (p < 0.05)

b NovoMix® 30 significantly less than BHI (p < 0.001)

c NovoMix® 30 significantly earlier than BHI (p < 0.05)

d NovoMix® 30 significantly earlier than Humalog® Mix25TM (p < 0.01)

Hermansen K et al. Diabetes Care 2002;25:883–888


Larger and more rapid increase in serum insulin with novomix 30

Larger and more rapid increasein serum insulin with NovoMix® 30

a Values for NovoMix® 30 are significantly different from BHI 30 (p < 0.001)

Hermansen K et al. Diabetes Care 2002;25:883–888


Improved postprandial glucose vs bhi 30 and humalog mix25 tm

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 with BHI and Humalog® Mix25TM

  • Well tolerated with no serious adverse events occurring related to treatment

Hermansen K et al. Diabetes Care 2002;25:883–888


Comparison of efficacy and safety of novomix 30 vs bhi 30 study design

Comparison of efficacy and safety of NovoMix® 30 vs. BHI 30: study design

NovoMix® 30 (n = 140)

Insulin-using type 1 and type 2 diabetic patients

(n = 294)

One screening visit; patients already using a twice-daily insulin regimen

BHI 30 (n = 151)

12 weeks

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


Improved postprandial glucose after 3 months

Improved postprandial glucose after 3 months

NovoMix® 30

*

p < 0.05

*

12

BHI 30

*

*

10

*

8

Blood glucose (mmol/l)

6

0

Pre-

Post-

Pre-

Post-

Pre-

Post-

Bedtime

0200 h

Breakfast

Lunch

Dinner

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


Significantly lower prandial glucose increment with novomix 30

3

2.5

2

1.5

1

0.5

0

Significantly lower prandial glucose increment with NovoMix® 30

p < 0.02 between treatment groups

(mmol/l)

Mean prandial glucose increment

NovoMix® 30

BHI 30

(n = 141)

(n = 128)

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


Improved postprandial control with novomix 30

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 2002;19(5):393–399


Novomix 30 vs nph in type 2 patients

NovoMix® 30 vs. NPHin type 2 patients

  • OHA only

Twice-daily NovoMix® 30

(n = 201)

  • NPH + OHA

  • NPH monotherapy

  • No treatment

Original treatment

Twice-daily NPH insulin

(n = 202)

16 weeks

7–14 days

2 weeks

Screening

Randomisation

Christiansen JS et al.Diabetes, Obesity & Metabolism 2003;5(6):445-452


Novomix 30 vs nph lower prandial glucose increment

Favours NPH

Favours

NovoMix® 30

NovoMix® 30 vs. NPH: lower prandial glucose increment

*

1

  • *p < 0.005

  • ** p < 0.0001

0.56

0.5

0

Difference in prandial glucose increment

between treatment groups (mmol/l)

-0.5

-0.69

-1

**

-1.5

Mean prandial glucose increment

-1.26

-1.33

**

**

-2

Breakfast Lunch Dinner

Christiansen JS et al.Diabetes, Obesity & Metabolism 2003;5(6):445-452


Greater hba 1c reduction with novomix 30 vs nph

Greater HbA1c reduction with NovoMix® 30 vs. NPH

NovoMix® 30

(n = 66)

NPH

(n = 66)

0.0

-0.2

-0.4

Change in HbA1c (%)

-0.6

-0.8

p = 0.03

-1.0

Christiansen JS et al.Diabetes, Obesity & Metabolism 2003;5(6):445-452


Novomix 30 offers better glycaemic control than nph

NovoMix® 30 offers better glycaemic control than NPH

  • Mean prandial glucose increment lower in NovoMix® 30 group (p < 0.0001)

  • Patients receiving NPH monotherapy benefit from switching to NovoMix® 30 (bid)

Christiansen JS et al.Diabetes, Obesity & Metabolism 2003;5(6):445-452


Superior postprandial control

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


The dual release insulin preparation

Return to contents slide

Superior hypoglycaemia profile


Comparison of efficacy and safety of novomix 30 vs bhi 30 study design1

Comparison of efficacy and safety of NovoMix® 30 vs. BHI 30: study design

NovoMix® 30 (n = 140, 39% type 1)

Insulin-using type 1 and type 2 diabetic patients

(n = 294)

One screening visit; patients already using a twice-daily insulin regimen

BHI 30 (n = 151, 32% type 1)

12 weeks

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


Improved postprandial glucose after 3 months1

Improved postprandial glucose after 3 months

NovoMix® 30

*

p < 0.05

*

12

BHI 30

*

*

10

*

8

Blood glucose (mmol/l)

6

0

Pre-

Post-

Pre-

Post-

Pre-

Post-

Bedtime

0200 h

Breakfast

Lunch

Dinner

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


Significantly lower prandial glucose increment with novomix 301

3

2.5

2

1.5

1

0.5

0

Significantly lower prandial glucose increment with NovoMix® 30

p < 0.02 between treatment groups

(mmol/l)

Mean prandial glucose increment

NovoMix® 30

BHI 30

(n = 141)

(n = 128)

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


Reduced major hypoglycaemia after 3 months

Reduced major hypoglycaemia after 3 months

50% relative

risk reduction

45

40

35

30

Number of

hypoglycaemic episodes

42

events

25

20

15

20

events

10

5

0

NovoMix® 30

BHI 30

(n = 153)

(n = 138)

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


Trend towards reduced minor nocturnal hypoglycaemic episodes

Trend towards reduced minor nocturnal hypoglycaemic episodes

p = 0.06

60

55

50

45

40

35

58

events

Number of

hypoglycaemic episodes

30

25

39

events

20

15

10

5

0

NovoMix® 30

BHI 30

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


Reduced hypoglycaemic profile with novomix 30

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 2002;19(5):393–399


Novomix 30 vs bhi 30 2 year safety in type 2 diabetes

NovoMix® 30 vs. BHI 30: 2-year safety in type 2 diabetes

NovoMix® 30 bid (n = 58)

Insulin-using type 2 diabetic patients (n = 125)

BHI 30 bid (n = 67)

0

24 Months

Boehm et al. Submitted to Eur J Int Med


Reduced major hypoglycaemia after 2 years

Reduced major hypoglycaemia after 2 years

p = 0.04

12

NovoMix® 30

BHI 30

p = NS

10

8

Patients with at least one major

episode (%)

6

4

2

0

1st year

2nd year

Year of study

Boehm et al. Submitted to Eur J Int Med


2 year efficacy and tolerability of novomix 30 in type 2 diabetes

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

  • An equivalent level of efficacy

  • More favourable balance between hypoglycaemia and hyperglycaemia in insulin-treated type 2 diabetes

Boehm et al. Submitted to Eur J Int Med


Novomix 30 vs bhi 30 4 year safety in type 2 diabetes

NovoMix® 30 vs. BHI 30: 4-year safety in type 2 diabetes

Insulin-using type 2 patients (n = 73)

NovoMix® 30 bid (n = 32)

BHI 30 bid (n = 41)

0 24 42 48

Months

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


Twice daily novomix 30 and bhi 30 gives stable metabolic control

Twice-daily NovoMix® 30 and BHI 30 gives stable metabolic control

NovoMix® 30

BHI 30

9.0

8.5

8.0

HbA1c (%)

7.5

7.0

0

0 3 6 12 18 24 30 36 42

Months

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


Hypoglycaemic episodes in patients completing the 4 year trial

Hypoglycaemic episodes in patients completing the 4-year trial

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


Superior hypoglycaemic profile vs bhi 30

Superior hypoglycaemic profile vs. BHI 30

  • No major hypoglycaemic episodes during second year of treatment

  • No nocturnal hypoglycaemic events during 4 years’ treatment


The dual release insulin preparation

Return to contents slide

Superior HbA1c control with oral medication


Novomix 30 in combination with metformin

NovoMix® 30 in combination withmetformin

NovoMix® 30 bid + metformin (n = 108)

(n = 329)

NovoMix® 30 bid (n = 107)

Metformin failures

(HbA1c 7.5–13.0%)

glibenclamide + metformin (n = 114)

0

16

Weeks

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


Demographic characteristics total population

Demographic characteristics (total population)

NovoMix® 30 plus metformin intype 2 diabetes

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


Improved hba 1c with novomix 30 combination in total population

p = 0.004

Improved HbA1c with NovoMix® 30 combination in total population

8.5

HbA1c difference of 0.6%

8

(%) following 16 weeks'

treament

7.5

1c

0

HbA

7

NM

NM+met

Met+su

Treatment group

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


Superior glycaemic control with novomix 30 metformin in poorly controlled patients hba 1c 9

p = 0.037

Superior glycaemic control with NovoMix® 30 + metformin in poorly controlled patients (HbA1c > 9%)

p = 0.033

8.5

8

(%)

1c

HbA

7.5

0

7

NM

NM+met

Met+SU

Treatment group

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


Lower insulin dose when used with metformin

7

6

5

4

3

2

1

0

0

1

2

3

4

Lower insulin dose when used with metformin

NovoMix® +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 2002;51(Suppl 2):A104


Significantly lower body weight for novomix 30 met vs novomix 30

p = 0.05

Significantly lower body weight* for NovoMix® 30 + met vs. NovoMix® 30

p = 0.0004

120

100

80

weight (kg)

60

End of trial mean body

40

* Mean body weights adjusted for baseline

20

0

NovoMix® 30

NovoMix® 30 + met

Met + SU

Kvapil M et al.Diabetologia 2002;45(Suppl 2):A18


Novomix 30 plus metformin is well tolerated

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 + met23

    • NovoMix® 30 alone20

    • Met + SU 28

  • No other safety concerns were raised

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


    Improved glycaemic control with novomix 30 combination

    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 2002;51(Suppl 2):A104


    Once daily dinnertime novomix 30 with metformin

    Once-daily (dinnertime) NovoMix® 30 with metformin

    Metformin + NovoMix® 30 od (n = 46)

    Run-in period – metformin (up to 2550 mg/day)

    Metformin + human insulin NPH od (n = 47) Follow-up

    Metformin + BHI 30 od (n = 47)

    Eligible patients: FPG  126 mg/dl

    –4 0 12 14Weeks

    Kilo C et al. J Diabetes Complications 2003;17(6):307-13


    Addition of insulin to metformin improves glycaemic control

    Addition of insulin to metformin improves glycaemic control

    Treatment group (+metformin)

    NovoMix® 30

    NPH

    BHI 30

    -1

    (%)

    1c

    -1.2

    Reduction in HbA

    -1.4

    Kilo C et al. J Diabetes Complications 2003;17(6):307-13


    Benefits of reaching fasting glycaemic targets

    Benefits of reaching fastingglycaemic targets

    Treatment (+ metformin)

    NovoMix® 30

    NPH

    BHI30

    0

    -0.5

    -1

    (%)

    Change in HbA1c from baseline

    -1.5

    -2

    FPG <7 mmol/l (n = 26)

    -2.5

    Kilo C et al. J Diabetes Complications 2003;17(6):307-13


    No major hypoglycaemic events during the study

    No major hypoglycaemic events during the study

    Kilo C et al. J Diabetes Complications 2003;17(6):307-13


    Addition of second therapy when glibenclamide fails i

    Addition of second therapy when glibenclamide fails (I)

    NovoMix®30 (BID) +

    glibenclamide (n = 22)

    Glibenclamide

    (7.5–15 mg/day)

    Type 2 patients, HbA1c 813%

    Metformin (850 mg OD) +

    glibenclamide (n = 24)

    Weeks

    0 6

    Raz I et al. Diabetologia 2002;45(Suppl. 2): A263


    Improved glycaemic control with addition of novomix 30 vs metformin

    Improved glycaemic control with addition of NovoMix® 30 vs. metformin

    GLI+NovoMix® 30

    GLI+NovoMix® 30

    GLI+MET

    GLI+MET

    0.0

    0.0

    –0.5

    –0.3

    –1.0

    –1.5

    –0.6

    Mean glucose reduction

    (mmol/l)

    –2.0

    HbA1c reduction (%)

    –0.9

    –2.5

    –3.0

    –1.2

    –3.5

    *

    p < 0.05

    –4.0

    –1.5

    Raz I et al. Diabetologia 2002;45(Suppl. 2): A263


    Addition of second therapy when glibenclamide fails ii

    Addition of second therapy when glibenclamide fails (II)

    NovoMix®30 (BID) +

    rosiglitazone (4 mg OD) (n = 26)

    Glibenclamide

    (7–15 mg)

    Type 2 patients, HbA1c (813%)

    Glibenclamide +

    rosiglitazone (4mg OD) (n = 23)

    Weeks

    0 6

    Raz I et al. Clin Ther 2003;25:3109-3123


    Improved glycaemic control with novomix 30 combination1

    Improved glycaemic control with NovoMix® 30 combination

    ROS+NovoMix® 30

    ROS+NovoMix® 30

    ROS+GLI

    ROS+GLI

    0.0

    0.0

    –0.5

    –0.3

    –1.0

    –1.5

    –0.6

    Mean glucose reduction

    (mmol/l)

    –2.0

    HbA1c reduction (%)

    –2.5

    –0.9

    –3.0

    –1.2

    –3.5

    –4.0

    –1.5

    *

    p < 0.05

    Raz I et al. Clin Ther 2003;25:3109-3123


    Treatment options when metformin fails

    Treatment options when metformin fails

    NovoMix®30 (BID) + metformin (OD) (n = 23)

    Metformin

    (1700–2550 mg)

    NovoMix® 30 (BID) + repaglinide 1 mg (OD) + metformin (OD) (n = 24)

    Glibenclamide 5 mg (OD) + metformin (OD) (n = 23)

    Weeks

    0 6

    Raz I et al. Manuscript in preparation


    Reduction in hba 1c after 6 weeks treatment

    Reduction in HbA1c after 6 weeks’ treatment

    MET+

    REP+

    NovoMix® 30

    MET+

    REP+NovoMix® 30

    MET+NovoMix® 30

    MET+

    GLI

    MET+NovoMix® 30

    MET+

    GLI

    0.0

    0.0

    –0.5

    –0.3

    –1.0

    –1.5

    Mean glucose reduction

    (mmol/l)

    –0.6

    HbA1c reduction (%)

    –2.0

    –0.9

    –2.5

    –3.0

    –1.2

    –3.5

    –1.5

    –4.0

    Raz I et al. Manuscript in preparation


    Novomix 30 oral agent is preferable to a second oral agent

    NovoMix® 30 + oral agent is preferable to a second oral agent

    • The addition of NovoMix® 30 to an oral agent was more effective in lowering average glucose than when a second oral agent was added

    • Addition of NovoMix® 30 also showed a trend to decrease HbA1c

    • All treatment therapies showed improvements in HbA1c

    Raz I et al. Diabetologia 2002;45(Suppl 2):A263


    Treatment options with novomix 30 when su therapy fails

    Treatment options with NovoMix® 30 when SU therapy fails

    NovoMix® 30 (BID) + pioglitazone (30 mg OD)

    SU mono or combination therapy

    (HbA1c 7.513.0%)

    NovoMix® (BID)

    Glibenclamide (515 mg, OD) +

    pioglitazone (30 mg OD)

    0 1 2 4 8 12 18

    Time (weeks)

    Screening

    Randomisation

    (SU therapy discontinued)

    Discontinuation of trial product

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


    Lower hba 1c with novomix 30 combination treatment

    Lower HbA1c with NovoMix® 30 combination treatment

    11.0

    NovoMix® 30

    10.5

    NovoMix® 30 + pioglitazone

    Glibenclamide + pioglitazone

    10.0

    9.5

    HbA1c (%)

    *

    *

    9.0

    8.5

    8.0

    7.5

    *p < 0.01

    7.0

    Week 18

    Screening

    Week 8

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


    Superior glycaemic control with novomix 30 combination therapy

    Superior glycaemic control with NovoMix® 30 combination therapy

    • At end of trial, NovoMix® 30 + pioglitazone was superior to glibenclamide + pioglitazone on almost all measures of blood glucose (p < 0.05–p < 0.001)

    • Significantly lower prandial BG increment for NovoMix® 30 + pioglitazone versus glibenclamide + pioglitazone (p < 0.05)

    • NovoMix® + pioglitazone superior to NovoMix® 30 in reducing dinner-related glucose

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


    Novomix 30 pioglitazone is effective in type 2 diabetes

    NovoMix® 30 + pioglitazone is effective in type 2 diabetes

    • NovoMix® 30 and pioglitazone is an effective treatment combination in type 2 diabetic patients

    • The combination of NovoMix® 30 and pioglitazone offers better glycaemic control than the combination of glibenclamide and pioglitazone and NovoMix® 30 only

    • The combination of NovoMix® 30 and pioglitazone is well tolerated and associated with a low incidence of nocturnal hypoglycaemia

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


    Novomix 30 is an effective add on therapy

    NovoMix® 30 is an effective add-on therapy

    • Superior glycaemic improvements when NovoMix® 30 added to metformin vs. addition of SU

    • Adding NovoMix® 30 (once-daily) to metformin is more effective for controlling blood glucose levels compared with adding NPH or BHI 30

    • Overall, adding NovoMix® 30 to a failing oral agent provides superior glycaemic control than adding another oral therapy


    The dual release insulin preparation

    Return to contents slide

    Convenience and flexibility


    Patient preference for novomix 30 compared with bhi 30

    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 (p<0.05)

    Home P et al, Diab Res Clin Pract 2000;50(Suppl 1):S37


    Postprandial dosing with novomix 30

    Postprandial dosing with NovoMix® 30

    NovoMix® 30, 0 min

    NovoMix® 30, +15 min

    BHI 30, –15 min

    BHI 30, 0 min

    Visit 1 2 3 4 5 6

    (Screening) (Randomisation) (Follow-up)

    Days

    between

    visits

    5–21 3–21 3–21 3–21 1–14

    Kapitza C et al. Diabet Med 2004;21(5):500-1


    Postprandial dosing efficacy with novomix 30

    Postprandial dosing efficacy with NovoMix® 30

    BHI 30(t = –15 min)

    6

    BHI 30(t = 0 min)

    NovoMix®30(t = 0 min)

    4

    NovoMix®30( t= +15 min)

    2

    Blood glucose (mmol/l)

    0

    –2

    –4

    0

    60

    120

    180

    240

    300

    Time (min)

    Kapitza C et al. Diabet Med 2004;21(5):500-1


    Postprandial dosing with novomix 301

    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 2004;21(5):500-1


    Novomix 30 allows flexible dosing

    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 2004;21(5):500-1


    Postprandial novomix 30 dosing in elderly patients

    Postprandial NovoMix® 30 dosing in elderly patients

    Run-in (n = 91)

    Preprandial dosing

    Preprandial dosing

    Postprandial dosing

    Postprandial dosing

    NovoMix® 30, bid, preprandial

    0 4 8 12 Weeks

    Warren et al.Diab Res Clin Pract, in press 2004


    Blood glucose levels did not differ between treatment groups

    Blood glucose levels did not differ between treatment groups

    200

    Preprandial dosing(NovoMix® 30, bid)

    180

    Postprandial dosing(NovoMix® 30, bid)

    160

    140

    n = 91

    p = NS in all cases

    120

    Blood glucose levels (mg/dl)

    100

    80

    60

    40

    20

    0

    Before

    breakfast

    Before

    dinner

    2 hrs after

    breakfast

    2 hrs after

    dinner

    Warren et al.Diab Res Clin Pract, in press 2004


    Postprandial novomix 30 is effective in elderly type 2 patients

    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 et al.Diab Res Clin Pract, in press 2004


    Comparison of novomix 30 flexpen with humalog mix25 tm pen

    Run-in (n = 133)

    NovoMix® 30 FlexPen®

    NovoMix® 30 FlexPen®

    Humalog® Mix25TM Pen

    Humalog® Mix25TM Pen

    –3

    0

    12

    24

    Weeks

    Comparison of NovoMix® 30 FlexPen® with Humalog® Mix25TM Pen

    Niskanen et al. Clin Ther 2004;26(4):531-540


    Novomix 30 flexpen is simple to use

    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 < 0.001

    Niskanen et al. Clin Ther 2004;26(4):531-540


    Novomix 30 flexpen is preferred over humalog mix25 tm pen

    NovoMix® 30 FlexPen® is preferred over Humalog® Mix25TM Pen

    Equally easy/

    either

    NovoMix® 30

    FlexPen®

    Humalog®

    Mix25TM

    Equally difficult/

    neither

    100

    90

    *

    *

    80

    70

    60

    50

    % of patients

    40

    30

    20

    10

    0

    Overall, which pen device do

    Overall, which pen device would

    you find easiest to use?

    you prefer to continue to use

    after this trial?

    * p < 0.001 compared with Humalog® Mix25TM Pen

    Niskanen et al. Clin Ther 2004;26(4):531-540


    Comparable efficacy and safety vs humalog mix25 tm

    Comparable efficacy and safety vs. Humalog® Mix25TM

    • A similar reduction in HbA1c was seen in the NovoMix® 30 and Humalog® Mix25TM treatment groups

    • Both treatments lowered postprandial glucose to a similar extent

    • The number of hypoglycaemic events did not differ significantly between treatment groups

    • Both treatment groups experienced few adverse events

    Niskanen et al. Clin Ther 2004;26(4):531-540


    Higher patient satisfaction with novomix 30 flexpen

    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 et al. Clin Ther 2004;26(4):531-540


    Comparison of flexpen with humalog kit tm

    Comparison of FlexPen® with Humalog® KitTM

    ”Device-naïve” patients

    Run-in (n = 58)

    FlexPen®

    FlexPen®

    Humalog® KitTM

    Humalog® KitTM

    0

    2

    4

    Days

    Both pens contained rapid-acting analogues, however, no insulin was injected during the testing procedure

    Asakura T & Seino H Diabetes Metab 2003;29:4S236


    Flexpen is more user friendly than humalog kit

    FlexPen® is more user-friendly than Humalog® Kit

    **

    **

    *

    *

    *

    250

    FlexPen®

    Humalog® Kit

    200

    * p < 0.01

    ** p < 0.001

    150

    100

    Total score

    50

    0

    Ease of

    pressing

    release

    button

    Ease of

    dose setting

    Number

    legibility

    Injection

    confirmation

    Simplicity

    Pen feature

    Asakura T & Seino H Diabetes Metab 2003;29:4S236


    More patients prefer flexpen to humalog kit

    More patients prefer FlexPen® to Humalog® Kit

    * p < 0.01

    90

    80

    70

    60

    50

    Patients (%)

    40

    30

    20

    10

    0

    FlexPen®

    Humalog® Kit

    No preference

    Device preference

    Asakura T & Seino H Diabetes Metab 2003;29:4S236


    Flexpen is simple to use

    FlexPen® is simple to use

    Patients preferred FlexPen® to Humalog® Kit 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 2003;29:4S236


    Comparison of flexpen vs vial syringe

    Comparison of FlexPen® vs vial/syringe

    Run-in

    Type 1 and type 2 patients

    (using vial/syringe)

    FlexPen® FlexPen®

    Vial/syringe Vial/syringe

    Randomisation (n = 108)

    0 4 8 12

    Weeks

    Korytkowski M et al. Clinical Therapeutics 2003;25(11):2836-48


    Patients prefer flexpen to vial syringe

    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 (p<0.05) preferred to continue using FlexPen®vs. vial/syringe

    74%*

    Korytkowski M et al. Clinical Therapeutics 2003;25(11):2836-48


    Flexpen is preferred to vial syringe in a number of injection parameters

    FlexPen® is preferred to vial/syringe in a number of injection parameters

    Easier to read dose

    FlexPen®

    Vial/syringe

    No preference

    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. Clinical Therapeutics 2003;25(11):2836-48


    Reduction in hba 1c with novomix 30

    * p<0.05

    Reduction in HbA1cwith NovoMix® 30

    9.5

    9

    (%)

    8.5

    1c

    8

    7.5

    Absolute HbA

    7

    6.5

    0

    Baseline (week 0)

    End of trial (week 12)

    Time point

    Korytkowski M et al. Clinical Therapeutics 2003;25(11):2836-48


    Flexpen is preferred to vial syringe

    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. Clinical Therapeutics 2003;25(11):2836-48


    Health care professionals opinion

    Health care professionals’ opinion

    82% of healthcare professionals preferred FlexPen®

    compared with two other prefilled pens

    100

    * p<0.01 vs. Humalog® pen and OptiSet® (n=102)

    82%*

    80

    Proportion of patients (%)

    60

    40

    14%

    20

    3%

    0

    FlexPen®

    Humalog® Pen**

    OptiSet®

    ** Same device as Humalog® Mix 25 pen

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


    Convenient and flexible dosing with novomix 30 flexpen

    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® toHumalog® Mix25TM

    • Patients with impaired manual dexterity and vision prefer FlexPen® to Humalog® Kit


    Efficacy and safety of novomix 30 in type 1 adolescents

    Efficacy and safety of NovoMix® 30 in type 1 adolescents

    NovoMix®30 (TID) + NPH (bedtime)

    Snack insulin (IAsp) was administered when required (n = male/female 37/49)

    Type 1 patients, 10-17 yrs

    HI + BHI + NPH (bedtime)

    Snack insulin (HI) was administered when required (n = male/female 43/38)

    0 2 weeks 16 weeks (Time)

    Mortensen H et al.Diabetes Metab 2003;29:4S227


    Efficacy of novomix 30 in adolescents

    Efficacy of NovoMix® 30 in adolescents

    • NovoMix® 30 significantly improved BMI in boys, but not in girls

    • Both treatments improved glycaemic control during the 16-week period : HbA1c decreased by ~0.2%

    • NovoMix® 30 tended to improve prandial glucose control more in boys than in girls

    • There was no between-treatment difference in rate of hypoglycaemia

    Mortensen H et al.Diabetes Metab 2003;29:4S227


    Novomix 30

    NovoMix® 30:

    • NovoMix® 30 provides improved postprandial glycaemic control compared to biphasic human insulin and Humalog® Mix25TM

    • NovoMix® 30 provides a superior hypoglycaemic profile to biphasic human insulin

    • NovoMix® 30 improves HbA1c when used in combination with oral medications

    • NovoMix® 30 is simple and convenient to use in clinical practice

    • NovoMix® 30 is effective and well tolerated in adolescents


    Publications abstracts used in this slide kit

    Brange J et al. Nature 1988;333:679–682

    Jacobsen L et al. Eur J Clin Pharm 2000;56:399–403

    Weyer et al. Diabetes Care 1997;20:1612–1614

    McSorley PT et al. Clin Ther 2002;24(4):530–539

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

    Hermansen K et al. Diabetes Care 2002; 25:883–888

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

    Christiansen JS et al.Diabetes, Obesity & Metabolism 2003;5(6):445-452

    Boehm B et al. Submitted to Eur J Int Med

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

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

    Kilo C et al. J Diabetes Complications 2003;17(6):307-13

    Raz I et al. Clin Ther 2003;25:3109–3123

    Raz I et al. Manuscript in preparation

    Raz I et al. Diabetologia 2002;45(Suppl 2):A263

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

    Kapitza C et al. Diabet Med 2004;21(5):500-1

    Warren et al.Diabetes Res Clin Pract, in press 2004

    Niskanen et al. Clin Ther 2004;26(4):531-540

    Asakura T & Seino H Diabetes Metab 2003;29:4S236

    Korytkowski M et al. Clinical Therapeutics 2003;25(11):2836-48

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

    Mortensen H et al.Diabetes Metab 2003;29:4S227

    Publications/abstracts used in this slide kit


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