2. Basal Bolus Regimen in T2DM
Prof. Dr. Hala Aly Gamal El Din Professor Of internal medicine Faculty of Medicine - Cairo University

3. Goals of Glucose Management
Targets for glycemic (blood sugar) control
ADA
AACE
A1c (%)
<7*
≤6.5
Fasting (preprandial) plasma glucose
mg/dL
<110 mg/dL
Postprandial (after meal) plasma glucose
<180 mg/dL
<140 mg/dL
R36/p34/P1/L15
Both the ADA and the AACE recommend tight glucose control for persons with diabetes, although their definitions vary.
Despite the findings of two large-scale trials, the DCCT and UKPDS, a universally agreed-upon set of glucose management goals has yet to be defined. While almost every diabetes management guideline includes the hallmark variables of A1c and fasting plasma glucose, there are slight variations in specific target values. The American Diabetes Association (ADA) currently recommends a target A1c of <7%, while the American Association of Clinical Endocrinologists (AACE) suggests aiming for a value of 6.5% or lower. The ADA proposes a target range for fasting plasma glucose levels between 90 and 130 mg/dL, while the AACE recommends levels below 110 mg/dL. Postprandial plasma glucose recommendations put forth by the two organizations are <180 and <140 mg/dL, respectively.
In addition to these standard variables, there are other important aspects of diabetes management that deserve consideration. Other important issues identified in the two landmark trials, both medically and from a quality of life perspective, include reducing the frequency of hyperglycemic excursions, minimizing the risk of hypoglycemia, especially nocturnal, and minimizing weight gain. Addressing these issues could have an impact on patient motivation and/or treatment compliance, increasing the chance of attaining A1c and plasma glucose goals.
References:
American Diabetes Association. Standards of medical care in diabetes – Diabetes Care. 2006;29(suppl 1):S4-S42. Implementation Conference for ACE Outpatient Diabetes Mellitus Consensus Conference Recommendations: Position Statement at ImplementationPositionStatement.pdf. Accessed January 6, 2006.
R5/pS10/T6
*<6 for certain individuals
Implementation Conference for ACE Outpatient Diabetes Mellitus Consensus Conference Recommendations: Position Statement at Accessed January 6, 2006.
AACE Diabetes Guidelines – 2002 Update. Endocr Pract. 2002;8(suppl 1):40-82.
American Diabetes Association. Diabetes Care. 2009;32(suppl 1)
R2/p3/P2 3 3

4. Relation between PPG control & Achieving A1C Goal
Adapted from Monnier L, Lapinski H, Collette C. Contributions of fasting and postprandial plasnma glucose increments to the overall diurnal hyper glycemia of Type 2 diabetic patients: variations with increasing levels of HBA(1c). Diabetes Care. 2003;26: 4 4

5. Difficult and Important!!
Moving from A1C 8.0% to 7.0%
Difficult and Important!!
20-25% of Patients Have A1Cs between 8.0% and 7.0%
Moving from A1C 8.0% to 7.0% - Reduces Serious Complications
UKPDS Study Results
Reduced microvascular complications (kidney, eye, etc.) by %
Reduced risk of heart attack by 16%
Reduced diabetes-related deaths by 21%
Challenge: More difficult to make improvements as A1C gets closer to 7.0%

6. Improving control reduces risks of long term complications
Every 1% drop in HbA1c can reduce long-term diabetes complications
43%
Lower extremity amputation or fatal peripheral vascular disease
37%
Microvascular disease
19%
Cataract extraction
16%
Heart failure
14%
Myocardial infarction
12%
Stroke
UKPDS: Stratton et al. BMJ 2000;32:405–12

7. Parenteral/inhaled agents
A1C reduction with
glucose – lowering medications
Oral agents
A1C (%)*
Sulfonylureas
1.5
Biguanides (metformin)
Glinides
1.0–1.5
Thiazolidinediones
0.8–1.0
DPP-IV inhibitors
0.5–0.9
α-Glucosidase inhibitors
0.5–0.8
Parenteral/inhaled agents
Insulin
≥2.5
Inhaled insulin
GLP analogues
0.6
Amylin analogues
*Monotherapy
DPP = dipeptidyl peptidase; GLP = glucagon-like peptide
Nathan DM. N Engl J Med. 2007;356:

8. Insulin is the most effective anti diabetic agent
Nathan DM. N Engl J Med. 2007;356:

9. Insulin therapy in T2DM indications
Significant hyperglycemia at presentation
Hyperglycemia on maximal doses of oral agents
Decompensation
Acute injury, stress, infection, myocardial ischemia
Severe hyperglycemia with ketonemia and/or ketonuria
Uncontrolled weight loss
Use of diabetogenic medications (eg, corticosteroids)
Surgery
Pregnancy

10. A clinical fact
Most Patients with T2DM will eventually need exogenous insulin to maintain recommended targets for glycaemic control
Starting insulin treatment in adults with Type 2 diabetes
RCN guidance for nurses 2004

11. When to Start Insulin First
ADA-EASD Consensus
SEVERELY CATABOLIC PATIENT
Hemoglobin A1C > 10%
FBS > 250 mg/dl (13.9 mmol/l)
Random consistently > 300 mg/dl (16.7 mmol/l)
Nathan et al. Diabetes Care 2006;29:

12. T2DM treatment Old paradigm by A1C level 7% 8% 9% 10% 7% Insulin
Diet and
exercise
Combination
oral agents
7%
Monotherapy
Insulin

13. New ADA/EASD treatment algorithm for Type 2 diabetes
Tier 1: Well validated core therapies
Lifestyle + Metformin +
Basal insulin
Lifestyle + Metformin +
Intensive insulin
At diagnosis:
Lifestyle +
Metformin
Lifestyle + Metformin +
Sulfonylureaa
STEP 1
STEP 2
STEP 3
Tier 2: Less well validated therapies
Lifestyle + Metformin +
Pioglitazone
No hypoglycaemia
Oedema/CHF
Bone loss
Lifestyle + Metformin +
Pioglitazone
Sulfonylureaa
Nathan DM, Buse JB, Davidson MB, et al. Diabetologia. 2009;52:17-30
Lifestyle + Metformin +
GLP-1 agonistb
No hypoglycaemia
Weight loss
Nausea/vomiting
Lifestyle + Metformin +
Basal insulin
Reinforce lifestyle interventions at every visit and check HbA1c every 3 months until HbA1c is <7 % and then at least every 6 months. The interventions should be changed if HbA1c is ≥7 %
aSulfonylureas other than glibenclamide (glyburide) or chlorpropamide bInsufficient clinical use to be confident regarding safety

14. The Ideal Basal Insulin
Mimics normal pancreatic basal insulin secretion
Long-lasting effect – 24 hours
Smooth, peakless profile
Reproducible and predictable effects
Reduced risk of nocturnal hypoglycemia
Once-daily administration 14

15. Levemir® FlexPen® ? Welcome! Thank you for joining us here today…
This is a momentous day for Levemir® because, unusually, we now have a second chance for a new beginning…
And just in case you’re thinking… here we go again, same old, same old…
Let me set you straight. When we tell you this is a new beginning for Levemir®, we mean just that. Nothing will ever be the same again…
Are you ready to hear more…? 15

16. Insulin Detemir (Levemir®)
LysB29(N-tetradecanoyl)des(B30)human insulin
Detemir Properties:
Neutral pH
Albumin binding
Long extended action
More within patient consistency
Less hypoglycemia
Less weight gain
Thr
Glu
Lys
Val
Phe
Asn
Leu
Gln
Tyr
Ser
Cys
Ile
Gly
Pro
Arg
Ala
His B1
A21 A1
B29
C14 fatty acid chain
(Myristic acid)
In insulin detemir, a 14-carbon (myristic acid) FA side chain is attached to Lysine at residue B29, with threonine at residue B30 removed.
Insulin detemir takes its name from: Des threonine + myristic (mir) acid 16

17. Mode of Action Injection site Blood Tissue
Use of Serum Carrier Protein (e.g. Albumin) to Extend time of action
Injection
site
Blood
Tissue
Carrier
Protein
Receptor
Carrier
Protein
Receptor
Hormone
Hormone
Hormone
Hormone
Carrier
Protein

18. Levemir® FlexPen® Designed to bind specifically to albumin
Albumin binding protracts:
Absorption of insulin detemir from the subcutaneous depot
Residency of insulin detemir in the circulation
Albumin binding buffers variability of action of insulin detemir
There are no safety concerns with albumin binding of insulin detemir or with changes to its insulin structure

19. Albumin binding of Levemir®
Myristic acid binds at fatty-acid binding sites of albumin
98.8% binding in human plasma
Safety of albumin binding
At therapeutic doses, insulin detemir occupies a tiny fraction of available
albumin binding sites, with more
than 60,000-fold excess albumin
over insulin
This 3D cartoon illustrates albumin binding in a capillary. It can be used alongside the other screen grabs from the insulin detemir animation if a more ‘graphic’ presentation is required.

20. Mode of prolonging action
Self association (hexameric)
Fatty acid side chains bind to albumin in injection depot
Albumin binding in circulation
Protracted absorption
‘Buffering’ effect and minor contribution to protraction

21. Why do we say Levemir™ is “predictable”?
Solution, acid pH, pain
Precipitation & de-precipitation is the mechanism of protraction:
so factors of precipitation and absorption remain
Glargine
Precipitation
Solution, neutral pH, no pain
No precipitation mechanism of protraction depends on increased self -association
Levemir™
Precipitation
No absorption factor – albumin binding buffers absorption

22. Variability in time-action profile of basal insulin
Study 1450.
Importantly, the time-action profile of insulin detemir has also been shown to be reproducible – significantly more so than NPH insulin or insulin glargine.
These data are taken from a comparative study in which patients underwent glycaemic clamps following 4 injections on 4 separate visits. Here we see three typical examples of the GIR curves required to maintain a glycaemic target following injection in three patients – one receiving insulin glargine, one NPH insulin and one insulin detemir.
Abstract:
Lower Within-Subject Variability of Insulin Detemir in Comparison to NPH Insulin and Insulin Glargine in
Subjects with Type 1 Diabetes
TIM C. HEISE 1 , LESZEK NOSEK 1 , EBERHARD DRAEGER 2 , ANNETTE STENDER 2 , BIRGITTE BIILMANN RØNN 2 , CHRISTOPH KAPITZA 1 , LUTZ HEINEMANN 1 .
1 Neuss, Germany, 2 Bagsvaerd, Denmark.
We compared the within-subject variability of the effect of the novel long-acting
insulin analogue insulin detemir (IDet) with that of NPH insulin and insulin
glargine (GL) in a randomized, controlled, parallel group, double blind study.
Fifty-four patients with type 1 diabetes (32 males; age 38±10 years (mean±SD);
BMI 24±2 kg/m 2 ; HbA 1c 7.5±1.2%; diabetes duration 18±9 years) received the
same dose (0.4 U/kg) of either NPH insulin, GL or IDet s.c. on four identical
study days under euglycemic glucose clamp conditions (target blood glucose
concentration 5.5 mmol/L). The pharmacodynamic and pharmacokinetic effects of
the basal insulin preparations were recorded for 24 and 28 hours post-dose,
respectively. IDet showed significantly less within-subject variability compared to
NPH and GL (2.5 and 1.8 fold lower CV for GIR-AUC(0–24h), respectively), see
table. Similar findings were also observed for pharmacokinetic parameters.
In conclusion, this first systematic investigation of the variability in the
pharmacodynamic and pharmacokinetic properties of the most commonly used
basal insulin preparations in type 1 diabetes shows significantly less within-subject
variability for insulin detemir. This suggests that this novel basal insulin will
provide a more predictable therapeutic effect compared to both NPH insulin and
insulin glargine.
Within-Subject Variability, expressed as Coefficients of Variations (CV) in %
Insulin Detemir NPH Insulin Insulin Glargine
Pharmacodynamics (assessed by Glucose Infusion Rates (GIR))
GIR-AUC (0–12h) * 46*
GIR-AUC (0–24h) * 48*
GIR max * 36*
Pharmacokinetics (assessed by plasma concentrations of insulin (INS), insulin
glargine and insulin detemir)
INS-AUC (0–12h)
INS-AUC (0–)
*: p<0.001 compared with insulin detemir (no statistical analyses were performed to compare
pharmacokinetic CVs). CVs were determined using an ANOVA model after log-transformation of the parameters.
GIR profiles following four non-consecutive injections of identical doses (0.4U/kg, thigh) in three patients
Heise T et al. Diabetes 2004;53:

23. TITRATE™Study
Levemir® once daily
Self-adjusted target FPG mg/dl
Main inclusion criteria:
Type 2 diabetes, ≥3 months
7%≤HbA1c≤9%
BMI ≤45 kg/m2
Age ≥18 years
Insulin naïve
Prior OAD
therapy
(n=122)
Levemir® once daily
Self-adjusted target FPG mg/dl
Screening period
(n=122)
Levemir® was initiated at 0.1 to 0.2 unit/kg or 10 units once daily at dinner or bedtime
Dose titration was based on the PREDICTIVE® 303 patient-directed self-titration algorithm
Patients continued on OAD therapy
Study Design: Treat to Target
This study was designed to prove that Levemir® can be successfully dosed once daily in Type 2 patient population and to investigate the use of the 303 algorithm using lower target fasting glucose levels
244 insulin-naïve patients with type 2 diabetes treated with OAD therapy (metformin± sulfonylurea ± glinides ± TZDs) were randomized to 1 of 2 FPG target–titration arms: mmol/L or mmol/L 1
Levemir 0.1 to 0.2 unit/kg or 10 units was used once daily at dinner or bedtime1
Patients continued their OAD use and self-titrated their insulin dose every 3 days according to the mean of self-measured FPG values the 3 previous days, using the forced titration algorithm described in the PREDICTIVE® (Predictable Results and Experience in Diabetes Through Intensification and Control to Target: An International Variability Evaluation) 303 study2
Blonde L et al. 2009; [manuscript under review].
2. Meneghini L., Koenen C., Weng W., Selam J.L. The usage of a simplified self-titration dosing guideline (303 Algorithm) for Levemir in patients with type 2 diabetes - Results of the randomized, controlled PREDICTIVE 303 study. Diabestes obes metab 2007; 9:
Blonde L et al; Diabetes Obes Metab Jun;11(6):623-31 23

24. HbA1C Improvement Mean HbA1c (%) 8.2 -1.22% reduction in HbA1C
7.99
6.93
6.77*
Mean HbA1c (%)
8.0
7.8
7.6
7.4
7.2
7.0
6.8
6.6
6.4
6.2
6.0
7.94
7.04
7.00*
FPG mg/dl
Mean HbA1C Reduction by Week: ITT population
Mean HbA1c at the end of study was 6.9% for the combined target groups.
In the mmol/L target group, HbA1c values decreased by 1.22% from baseline, while HbA1cvalues decreased by 0.94% from baseline in the mmol/L group at Week 20, LOCF Decreases in HbA1c were significantly different both from baseline and between the 2 target groups (LS mean difference = ‑0.271; 95% CI: , ; P=0.0019)
Once-daily Levemir® decreased HbA1c to a mean of 6.9%
A reduction in HbA1C of -1.2% in patients as high as 9% (range 7-9)
FPG mg/dl
Baseline 12 20
Time (study week)
*Change in both groups , p=0.019 at 20 weeks
Blonde L et al; Diabetes Obes Metab Jun;11(6):623-31
Reference
Data on file. Novo Nordisk Inc., Princeton, NJ.

25. Low rates of hypoglycaemia with once-daily Levemir®
Hypoglycaemic Events
Low rates of hypoglycaemia with once-daily Levemir®
p=NS
FPG mg/dl
FPG mg/dl
Events per subject/year
p=NS
Hypoglycaemia occurred with very low rates
Rates of Overall and Nocturnal Hypoglycemia: Safety Analysis
The overall rates of hypoglycemia episodes were low and comparable between target groups
Nearly all hypoglycemic events were considered minor or symptoms only
A single major hypoglycemic event was reported by a subject in the mg/dL target group
Hypoglycaemic events
One major hypoglycaemic event was reported
by subject in the mg/dl target group
Blonde L et al; Diabetes Obes Metab Jun;11(6):623-31
References
Blonde L et al. 2009; [manuscript under review]. Data on file. Novo Nordisk Inc., Princeton, NJ.

26. Change in weight Insulin detemir NPH insulin 1 0.55 -0.06 -0.56 -1
25
>25-30
>30-35
>35
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5 1
0.55
-0.06
-0.56 -1
-0.96
-1.51
Data from the clinical study shown on the left side of the graph illustrates how insulin detemir incurs a weight sparing advantage that is correlated with BMI; patients in the highest BMI categories, gained the least weight.
On the right side of the slide, we can see how these data from a randomised controlled trial are, in fact, also seen in the everyday clinical setting.   -2 n=
<25
25–<27
27–<29
29–<31
≥31
Baseline BMI
Baseline BMI
Philis-Tsimikas et al. Clin Ther 2006
Dornhorst et al. Int J Clin Pract 2008 26

27. Titration at a once-daily dose
Mean 3-day FPG 3
3 units
Increase dose 3
Units
Above target
FPG Target range
70-90 mg/dL or mg/dL
no adjustment
Maintain dose
The 303 algorithm was shown to be effective and simple to use in the PREDICTIVE 303 study. This was therefore adopted in a study of patients driven titration with Levemir.
303 Titration Algorithm
In the original version of the 303 chart, the FPG titration target used by Meneghini et al ( mmol/L ) is represented as the target range with titration instructions positioned to the right of “0 maintain dose.” In this newly adapted version, the dual FPG targets from the Blonde trial are included, allowing physicians to choose the target ( mmol/L or mmol/L ) to better customize therapy for each patient. Physicians can help their patients with type 2 diabetes get to goal with either FPG target. 3
Below target
Units
Decrease dose
3 units
Patients who experienced hypoglycaemia reduced their daily dose by 3 units
Reference
Data on file. Novo Nordisk Inc., Princeton, NJ.

28. Insulin analogues compared
Insulin receptor affinity
IGF-1R affinity
Insulin receptor off rate
Metabolic potency
Mitogenic potency
Human insulin
=100
Insulin aspart
92 ± 6
81 ± 9
81 ± 8
101 ± 2
58 ± 22
Insulin detemir
18 ± 3
16 ± 1
204 ± 9 27 11
Kurtzhals P, et al. Diabetes 2000; 49: 999 28 28

29. Insulin analogues compared
Insulin receptor affinity
IGF-1R affinity
Insulin receptor off rate
Metabolic potency
Mitogenic potency
Human insulin
=100
Insulin aspart
92 ± 6
81 ± 9
81 ± 8
101 ± 2
58 ± 22
Insulin lispro
84 ± 6
156 ± 16
100 ± 11
82 ± 3
66 ± 10
Insulin glargine
86 ± 3
641 ± 51
152 ± 13
60 ± 3
783 ± 13
Insulin detemir
18 ± 3
16 ± 1
204 ± 9 27 11
Kurtzhals P, et al. Diabetes 2000; 49: 999 29 29

30. ONCE- DAILY DOSING1,3 OPTIMAL HbA1c Control1,2 LOW RISK OF HYPOS3,4
FlexPen® TRUSTED BY MILLIONS6,7
LESS
WEIGHT
GAIN4,5
LOW RISK OF HYPOS3,4
OPTIMAL HbA1c
Control1,2
ONCE-
DAILY DOSING1,3

31. Summary
Treatment with basal analogues enables patients to reach HbA1c target with low rate of hypoglycaemia
HbA1c improves but some patients need more
Levemir® + OD is associated with:
reduced hypoglycemia in comparison to NPH, and
reduced weight gain in comparison to any other basal insulin.
Initiation of Levemir® + OD with algorithm is effective, simple and safe.

32. Bolus Insulin
Today I’m going to show you results from real-world observational studies that analyzed Levemir® compared to glargine. 32

33. Physiologic Insulin Secretion: 24-hour Profile
(µU/mL)
Basal insulin
Breakfast Lunch Dinner 50 25
Prandial insulin
150
Time of day
Glucose
(mg/dL)
100 50 7 8 9 10 11 12 1 2 3 4 5 6 AM PM
Basal glucose
Prandial glucose
When we consider glucose control, we need to focus on both postprandial and basal requirements. This slide illustrates the normal physiologic response of glucose and insulin to meals, which highlights the need for both basal and meal-time insulin.
Meal insulin release occurs in response to nutrient ingestion.
Basal insulin is continuously secreted over a 24-hour period.
In the past, we have had to make due with various insulin formulations that did not have adequate pharmacokinetics to duplicate these profiles. However, within the past few years, new insulin analogs that provide more physiologic profiles have been developed. 33

34. Limitations of Human Regular Insulin
Slow onset of action
Requires inconvenient administration: 20 to 40 minutes prior to meal
Risk of hypoglycemia if meal is further delayed
Mismatch with postprandial hyperglycemic peak 34

35. Structure of insulin aspart (NovoRapid®)
NovoRapid® is designed for low self-association
to allow rapid absorption
Read from slide. 35 35

36. Absorption: human insulin vs. Insulin aspart- t
ype
concent r
ation (M)
hexamer 10 –3 10 T - t
ype –4
hexamer
This is purely schematic to illustrate
absorption of molecules 10 –6
Dimer
Absorption 10 –8
Monomer
Capillary membrane

37. NovoRapid® is designed for rapid, flexible control
Rapid absorption
Meal time flexibility
Rapid time to maximum effect
Efficacy
Rapid return to baseline insulin level
Safety (Less Hypos)
BI Yu- fang, ZHAO Lie-bin et al. Compare efficacy and safety of insulin aspart and Novolin R delivered with
CSII in 21 Chinese diabetic patients.Chin Med 2007;120(19): 37

38. Estimated Pharmacokinetics of Current Insulin Preparations
Onset
Peak
Effective Duration
Rapid acting analog
<15 min hr
3 hr
Human Regular Insulin
0.5-1 hr
2-3 hr
3-6 hr
Barnett AH, Owens DR. Lancet. 1997;349: White JR, et al. Postgrad Med. 1997;101:58-70.
Kahn CR, Schechter Y. In: Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 1990:
Coates PA, et al. Diabetes. 1995;44(Suppl 1):130A. 38

39. Bolus Insulin for Pre-prandial Administration
Clinical Benefits
Precise dosing
Optimal glucodynamics
Reduced risk of hypoglycemia (day and night)
Desirable Kinetic Characteristics
Predictable, reproducible time- action profile
Rapid onset of action
Short duration of action
In type 2 diabetes there is an impairment of beta cell (ß-cell) function resulting in a decrease in insulin secretion and an impairment of insulin with subsequent insulin resistance. 39

40. NovoRapid® FlexPen®
Today I’m going to show you results from real-world observational studies that analyzed Levemir® compared to glargine. 40

41. Insulin Aspart vs. Regular Human Insulin: Effect on A1C
8.5
8.0
7.5
Insulin Aspart
Regular Insulin
A1C (%) • * 3 6
Time (months)
Data represent mean ± SEM
* P < 0.05 41

42. Effect of NovoRapid® versus Actrapid® on PP myocardial perfusion in type 2 diabetes
Blood-
Flow
Healthy group people
T2D Patients
Fasting
Posprandial
Scognamiglio R et. al. Diab Care 2006;29:95–100

43. Cumulative CV events in 374 Japanese T2 patients after 4.5 years
Nippon ultrarapid Insulin and diabetic Complication Evaluation (NICE) Studie
Cumulative CV events in 374 Japanese T2 patients after 4.5 years
Nishimura M et al. Diabetologia 2008;51(Suppl1):S ;51(Suppl1):S543

44. NovoRapid®: approved for every stage of life, from children aged 2 years to the elderly2
Approved for use in abroad range of patients
For patients with Type 1 diabetes2
For patients with Type 2 diabetes2
For patients using an insulin pump2
Even patients requiring special consideration
For use in pregnancy- can be used during lactation2
For use in the elderly2
For use in children aged 2 years and above2
For use in special population with renal or hepatic imparement2,3
Read from slide. 44 44

45. NovoRapid® : helps T2DM patients attain and maintain their HbA1c goals4
6.9% median HbA1c
achieved by patients at 3 years
1.2% reduction in HbA1c from baseline4
63% of patients achieved ADA target <7% over 3 years4
Reduced mean PPG levels4
The addition of NovoRapid® significantly reduced the mean
PPG level by 67 mg/dL (3.72 mmol/L)4 45

46. NovoRapid® : Reduced rate of nocturnal hypoglycaemia
72% less major nocturnal
hypoglycaemia in patients with
type 1 diabetes6
24% Lower risk of nocturnal hypoglycaemia was confirmed by a meta-analysis of 3,727 T1DM patients in randomized, controlled trials conducted over 10 years of clinical experience with NovoRapid®7
Reduced rates of hypoglycaemia, even in pregnant women8
Initiation of NovoRapid® preconception may result in lower risk of severe hypoglycaemia in pregnant women with type 1 diabetes8
Nocturnal events 46

47. NovoRapid® :pre and post meal dosing allows patients to treat according to lifestyle9
Depending on their lifestyle and eating habits, some patients require more treatment flexibility10-12
NovoRapid® enabled an overall improved quality of life with increased flexibility compared with regular human insulin T1DM10
Since children may have unpredictable eating habits, parents preferred NovoRapid® over regular human insulin11
Pregnant women with T1DM preferred NovoRapid® for more flexibility12 in their treatment9
Read from slide. 47 47

48. FlexPen® : trusted by millions worldwide13,14
Next Generation FlexPen® from Novo Nordisk offers
Read from slide. 48 48

49. New features of FlexPen

50. Glulisine “zinc-free” counter - what data do we have?
Approved shelf-life: aspart vs. glulisine
The approved shelf-life is greater for NovoRapid® than for Apidra® in both the Europe and US
Furthermore, once in use NovoRapid® remain stable for 28 days at 30°C while Apidra® must be stored at no greater than 25°C
European Label
US Label
Shelf-life (2-8°C)
In-use
NovoRapid®/NovoLog®
30 months
28 days <30°C
Insulin glulisine
24 months
28 days <25°C
Glulisine US label April 07, European label July 05
NovoRapid Core Data Sheet, version 10, 2007

51. After 10 years of study and use2, no other rapid- acting insulin is part of so many lives1
Approved for every stage of life, from children aged 2 years to the elderly2
Helps patients attain and maintain their HbA1c goals4
NovoRapid® significantly reduced major nocturnal hypoglycaemia versus regular human insulin by 72%6,7
Pre- and post-meal dosing allows patients to treat according to lifestyle10
FlexPen®: trusted by millions worldwide14,15
Read from slide. 51 51

52. Summary
Today I’m going to show you results from real-world observational studies that analyzed Levemir® compared to glargine. 52

53. Timely addition of prandial insulin reflects a meal plus basal insulin coverage
Tight glycaemic control can be achieved and maintained with low rates of hypoglycaemia and minimal weight gain, using insulin Detemir (Levemir®) OD first, then adding short acting analogue insulin (insulin Aspart, NovoRapid®), stepwise or with all meals according to 1-0-1
Initiation and intensification of insulin therapy in type 2 diabetes can be done safely, effectively and conveniently

54. References:
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