Insulin degludec/insulin aspart-an overview of co-formulation insulin analogue and use in Ramadan by Dr Shahjada Selim_BSMMU

1. Insulin degludec/insulin aspart-
an overview of co-formulation insulin
analogue and use in Ramadan
Dr Shahjada Selim
Assistant Professor
Department of Endocrinology
Bangabandhu Sheikh Mujib Medical University, Dhaka
Presentation title Date 1

2. Diabetes is a huge and growing problem, and
the costs to society are high and escalating
382 million people have
diabetes
By 2035, this number will
rise to 592 million

3. Diabetes: Facts and figures
Almost half of all people with
diabetes live in just three
countries
China
Indian Subcontinent
USA
About 6 Million people of
Bangladesh are affected
by Diabetes
(5.9 million as per IDF 2014)
Source: IDF Diabetes Atlas Sixth Edition, International Diabetes Federation 2013

4. 4
Better HbA1c control is associated with reductions
in long-term health 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
14%
Myocardial
infarction
16%
Heart failure
12%
Stroke
UKPDS 35: Stratton et al. BMJ 2000;32:405–12

5. 5
The worldwide challenge of
glycaemic control: mean
HbA1C in type 2 diabetes
Canada 7.36–8.7%11
Latin America 7.6%1
US 7.2%7
China 9.5%11
India 8.7–9.6%9,11
Japan 7.05–9.6%11
Korea 7.9–8.7%4
Russia 9.6%11
Spain 9.2%8
Sweden 8.7%3
Turkey 10.6%3
UK 8.510–9.8%2
Germany 8.42–9.2%8
Greece 8.911–9.7%3,8
Italy 8.4%11
Poland 9.0%11
Portugal 9.7%3
Romania 9.9%3
1. Lopez Stewart et al. Rev Panam Salud Publica 2007;22:12–20; 2. Kostev & Rathmann Primary Care Diabetes 2013;7:229–33; 3. Oguz et al. Curr Med Res Opin
2013;29:911–20; 4. Ko et al. Diabet Med 2007;24:55–62; 5. Arai et al. Diabetes Res Clin Prac 2009;83:397–401; 6. Harris et al. Diabetes Res Clin Pract 2005;70:90–7;
7. Hoerger et.al. Diabetes Care 2008;31:81–6; 8. Liebl et al. Diabetes Ther 2012;3:e1–10; 9. Shah et al. Adv Ther 2009;26:325–35; 10. Blak et al. Diabet Med
2012;29:e13–20; 11. Valensi et al. Int J Clin Pract 2008;62:1809–19

6. Progressive treatment should follow
progressive disease

7. 7
Type 2 diabetes is a progressive disease
HOMA, homeostasis model assessment
Adapted from: UKPDS 16. Diabetes 1995;44:1249–58

8. 8
30
49 55 60
70
70
51 45 40
30
<7.3 7.3-6.4 8.5-9.2 9.3-10.2 >10.2
Recommended insulin therapy considers the
contribution of FPG and PPG in driving HbA1c
levels
Contributiontooverall
hyperglycaemia(%)
HbA1c value quintiles (%)
FPG
PPG
• The relative contribution of
PPG becomes increasingly
important for maintaining
overall glycaemic control with
lower HbA1c
1
• When glycaemic goals are not
obtained despite successful
basal insulin dose titration,
treatment should be intensified
by the addition of a prandial or
biphasic insulin2
FPG, fasting plasma glucose; PPG, postprandial glucose
1. Monnier et al. Diabetes Care 2003;26:881-5; 2. Swinnen et al Diabetes Care 2009;32 (Suppl. 2):S253-9

9. 9
The addition of mealtime coverage is needed
when basal insulin is no longer enough
8:00
75
8:004:00 12:00 16:00 20:00 24:00 4:00
50
25
0
Time
PlasmaInsulin
(μU/mL)
Basal Insulin
DinnerLunch
Breakfast
This may lead to hypoglycaemia
if food changes or meals are missed
Mealtime insulin response is missing;
high postprandial readings at every meal
Garber et al. DOM 2009;11(Suppl. 5):14-8

10. 10
Insulin optimisation and intensification should
follow disease progression
Betacell
function(%)
Treatment optimisation and intensification
Lifestyle + OADs
Basal and 1-4 bolus Or Premix
Basal insulin + OADs
Titrate dose to reach/maintain glycaemic targets
Intensify for mealtime insulin coverage
Initiate
Optimise
Intensify
Schematic diagram adapted from Kahn et al. Diabetologia 2003;46:3–19; Inzucchi et al. Diabetologia 2012;55:1577-96

11. ADA/EASD 2015 – guidelines for managing hyperglycaemia

12. Rationale for combining basal and bolus
insulin in a single injection
• Type 2 diabetes is a progressive disease
• The addition of insulin to provide mealtime coverage is needed when
basal insulin is no longer enough1
• Existing basal and bolus regimens offer basal and precise
postprandial glucose control but as separate injections2,3
• A combination of basal and bolus insulin could allow for a simple
regimen with fewer injections 2
1. Garber et al. Diabetes Obes Metab 2009;11(suppl 5):14–18; 2. Inzucchi et al. Diabetes Care 2012;35:1364–1379; 3. Nathan et al. Diabetes Care
2009;32:193–203

13. 1. Summary of Product Characteristics (SPC)
2. Jonassen I et al., Ultra-long acting insulin degludec can be combined with rapid-acting insulin aspart in a soluble co-formulation (Abstract). J Pept Sci
2010;16:32
3. De Rycke A et al., Degludec – First of a New Generation of Insulins. European Endocrinology 2011;7(2):84–7
…basal insulin with an ultra-long
duration of action, degludec, and a
well-established mealtime insulin,
aspart 1,2,3
In one pen, for people with
type 2 diabetes
IDegAsp is the first combination of two
Insulin analogues…

14. Co-formulation vs premixed preparation
Preparation Co-formulation Premixed preparation
Definition Formulation of two separate
components, which maintain distinct
identity
Mixture of two components, which
are unable to maintain distinct
identity
Appearance Clear Cloudy
Proportion Pre-determined Pre-determined
Kinetics/Dynamics Both components maintain distinct
PK/PD profiles
PK/PD profile of both components
may merge
Scope Allows co-formulation of separate
classes of drugs
Does not allow mixing of different
classes of drugs
Examples degludec+ aspart;
degludec+liraglutide;
glargine+lixisenatide
Biphasic human Insulin / Insulin
aspart/ lispro

15. Insulin detemir and insulin glargine cannot be
co-formulated with commercially available
rapid-acting analogues
1. Lantus® US Prescribing Information. Sanofi April 2010; 2. Jonassen et al. Pharm Res 2012;29:2104–2114
Insulin detemir2
Insulin detemir Insulin aspart
Mixed hexamers
pH 7.00.0 14.0
Insulin glargine is
soluble at pH 4
Rapid-acting analogues
soluble at pH 7.4
Insulin glargine1

16. • Forms stable dihexamers and does not interact with hexamers of insulin aspart
• Has a flat and stable glucose-lowering effect at steady state
• Formulated at neutral PH similar to rapid-acting insulin analogues
Ultra-long-acting insulin degludec- candidate
for co-formulation

17. Half-life of insulin degludec is twice as
long as that of insulin glargine
1. Heise et al. Diabetes Obes Metab 2012;14:944–950; 2. Heise et al. Diabetes 2012;61(suppl 1):A259;
3. Heise et al. Diabetes Obes Metab 2012;14:859–864
Flat time-action profile in type 2
diabetes at steady state1
Day-to-dayvariability
(coefficientofvariation%)
Variability in glucose-lowering effect
over 24 hours at steady state3
IDeg variability is four-fold
lower than IGlar
54320 1 6
Days since first dose
IDegserumconcentration
ProportionofDay6level
(%)
0
Type 2 diabetes
0 1 2 3 4
ProportionofDay4level
(%)
120
0
Days since first dose
Type 1 diabetes
Insulin degludec concentration reaches
steady state in 3 days2
120
The mean half-life of insulin
degludec is 25.4 hours
compared with insulin
glargine, which has a half-
life of 12.1 hours1

18. IDegAsp
A soluble co-formulation of insulin degludec and insulin aspart
Havelund et al. Pharm Res 2015 Jan 8 [Epub ahead of print]
IAsp
hexamers
Phenol1
IDeg
dihexamers
IDeg
multihexamers IAsp
monomers
No phenol1
Slow
dissociation
Subcutis
Capillary
Rapid
dissociation
IDeg IAsp
In subcutaneous depot
IDeg di-hexamers (70%)
IAsp hexamers (30%)
Formulation
It is not a premix insulin

19. 19
Ryzodeg® 0.3 U/kg BID
Injections
The flat and stable
basal coverage beyond 24
hours of insulin degludec
Time (in hours)
Glucoseinfusionrate
(mg/kg*min)intype1patients
The mealtime control of insulin aspart
8
6
4
2
0
0 24
Ryzodeg® dosed twice daily for type 2 patients
provides basal coverage and control for two main
meals13,14,19
Simulation of glucose-lowering effect of Ryzodeg® dosed twice daily19
Please see study design 1 on slide 26

20. IDegAsp shows distinct prandial and basal
glucose lowering effects compared with BIAsp30
n=22 for IDegAsp; n=24 for BIAsp 30
T1DM, type 1 diabetes
1. Heise et al. Diabetes Ther 2014;5:255–265; 2. Heise et al. Diabetes 2013;62 (suppl 1):A241 (abstract 947-P)
Mean glucose infusion rates for IDegAsp and BIAsp 30 in subjects with T1DM
Dose: 0.6 U/kg
IDegAsp (steady state)110
0
Glucoseinfusionrate(mg/([kg•min])
4 8 12 16
8
6
4
0
2
Time since injection (hours)
20 24
Glucoseinfusionrate(mg/[kg•min])
Time since injection (hours)
BIAsp 30 (single dose)210
0 4 8 12 16
8
6
4
0
2
20 24
Shoulder effect

21. 21Results from studies NN2004-1418 and NN5401-1959 in patients with T1DM
Profile: IDegAsp vs BIAsp 30 & BHI30
BHI 30
IDegAsp
11
Nominal time (h)
0 1 2 3 4 5 6 7 8 9 10 12 13 14 15 16 17 18 19 20 21 22 23 24
Glucoseinfusionrate
(mg/kg/min)
0
1
2
3
4
5
6
7
8
9
10
BIAsp 30

22. PK profiles of IDeg were similar for subjects
with normal and impaired renal function
• Kiss I et al. Clin Pharmacokinet. 2014; 53: 175–183
Mean total exposure to IDeg (AUCIDeg,0-120) following single
dose of IDeg in different renal function groups
1,000,000
100,000
10,000
Normal
Renal function group
Mild
Moderate
Severe
Creatinine clearance (mL/min)
10 100 1000
AUCIDeg,0–120h,SD

23. IDeg pharmacokinetics at steady state are similar to
simulated data from hepatic and renal impairment
studies
• 1. Kiss I et al. Clin Pharmacokinet. 2014; 53: 175–1832. Arold G et al. Clin Drug Investig. 2014 Feb;34(2):127-3
IDeg at
steady
state1
Simulated
steady state in
renal
impairment1
Simulated
steady state in
hepatic
impairment2
0
0
4 8 12 16 20 24
2000
4000
6000
8000
10000
Renal function group
Normal
Mild
Moderate
Severe
Hepatic function group
Normal
Child–Pugh A
Child–Pugh B
Child–Pugh C
Time since injection (hours)
0
0
4 8 12 16 20 24
2000
4000
6000
8000
10000
Insulindegludecserumconcentration(pmol/L)
0
0
4 8 12 16 20 24
2000
4000
6000
8000
10000
IDeg 0.4 U/kg

24. Total daily starting dose for
IDegAsp is 10 units with
main meal(s) followed by
individual dosage
adjustments
Type 2 diabetes Type 1 diabetes
The recommended starting
dose of IDegAsp is 60–70%
of the total daily insulin
requirements
IDegAsp should be used once
daily with the main meal and
short-/rapid-acting insulin
should be used at the
remaining meals, followed by
individual dosage
adjustments
Dosing of IDegAsp: Initiation
Ryzodeg® Summary of Product Characteristics 2013

25. Patients can be converted to
IDegAsp at the same total
insulin dose as the patient’s
previous total daily dose1
Patients can be converted
unit-to-unit to IDegAsp dosed
twice daily at the same total
insulin dose as the patient’s
previous total daily dose1
OD
1:1
OD
Basal/Premix IDegAsp
BID
1:1
≥BID
Basal/Premix IDegAsp
Dosing of IDegAsp: Transfer from
other insulins
Ryzodeg® Summary of Product Characteristics 2013

26. Phase 3 BID: Titration algorithm1,2
Pre-breakfast/pre-main evening
meal plasma glucose*
Adjustment
mmol/L mg/dL U
<3.1† <56† –4 (If dose >45U, reduce by 10%)
3.1–3.9† 56–69† –2 (If dose >45U, reduce by 5%)
4.0–4.9 70–89 0
5.0–6.9 90–125 +2
7.0–7.9 126–143 +4
8.0–8.9 144–161 +6
≥9.0 ≥162 +8
*Mean of three consecutive days’ measurements; †Unless there is an obvious explanation for the low value, such as a missed meal
1. Fulcher et al. IDF 2013. Poster P-1399; 2. Christiansen et al. IDF 2013. Poster P-1395

27. Ramadan Guidelines
for Patients with Diabetes Mellitus

28. Fasting is a worldwide custom practiced for
religious and cultural reasons122
28
Religion Examples of fasting practices2–5
Muslim Ramadan: fasting during daylight hours for 29–30 days2,3
Jewish Yom Kippur and Tish’ah B’av: single days of fasting4
Hinduism Single days of fasting4
Christianity Ash Wednesday and Good Friday: single days of fasting4
Mormon Fasting once a month for a single day5
Healthy adult Muslims fasting during the month of Ramadan abstain from food,
water, or use of oral medications between dawn and sunset for 29–30 days every
year2,3
1Fasting can range from restricting certain foods to complete abstinence from all food and drink: 1Fazel M . J R Soc Med 1998;91:260–63;
2Al-Arouj M et al. Diabetes Care 2010;33:1895–902; 3Salti I et al. Diabetes Care 2004;27:2306–11; 4Green V. Br J Nursing 2004;13:658–
62; 5Horne BD et al. Am J Cardiol 2008; 102:814–19.

29. A large number of Muslim patients with diabetes fast
during Ramadan
29
• The global prevalence of diabetes is projected to increase in emerging economies,
including those with large Muslim populations4,5
• The pattern of daytime fasting and night-time meals and use of anti-diabetic
treatment increases the risk of complications, including hypoglycaemia in patients
with diabetes2,3
• Although the consensus from religious and medical leaders is that Muslims with
diabetes are generally not obliged to fast6 many choose to do so2,3
1.6 billion
(2010)
2.2 billion
(2030)
Global Muslim population1
1The Pew Forum on Religion & Public Life. http://www.pewforum.org/The-Future-of-the-Global-Muslim-Population.aspx (Accessed
March 2013); 2Al-Arouj M et al. Diabetes Care 2010;33:1895–902; 3Salti I et al. Diabetes Care 2004;27:2306–11; 4IDF Diabetes
Atlas 5th edition. www.idf.org/diabetesatlas/5e/the-global-burden (Accessed March 2013); 5Whiting DR et al. Diabetes Res Clin Pract
2011; 94: 311–21; 6Beshyah SA. Ibnosina J Med Biomed Sci 2009;1:58–60

30. There are risks associated with fasting in patients
with diabetes
30
Hypoglycaemia:
due to decreased or irregular food
intake together with the use of anti-
diabetic medication;1–3 this has a
negative impact on patient morbidity,
mortality & QoL3–9
Hyperglycaemia:
due to excessive glycogen breakdown,
increased gluconeogenesis and
reduced doses of antidiabetic
medication1,2
Dehydration:
caused by limited fluid intake, as well
as osmotic diuresis produced by
hyperglycaemia1
Ketoacidosis:
due to increased ketogenesis1,2
Risks of fasting in patients with diabetes :
21
3 4
1Al-Arouj M et al. Diabetes Care 2010;33:1895–902;2Salti I et al. Diabetes Care 2004;27:2306–11; 3Amiel SA et al. Diabet Med
2007;25:245–54; 4Whitmer RA et al. JAMA 2009;301:1565–72; 5Bonds DE et al. BMJ 2010;340:b4909; 6Barnett AH. Curr Med Res
Opin 2010;26:1333–42; 7Foley JE et al. Vasc Health Risk Manag 2010;6:541–8; 8Begg IS et al. Can J Diabetes 2003;27:128–40;

31. 31
1Begg IS et al. Can J Diabetes 2003;27:128–40 2Bonds DE et al. BMJ 2010;340:b4909; 3Barnett AH. Curr Med Res Opin
2010;26:1333–42;
4Jönsson L et al. Value Health 2006;9:193–8; 5Foley JE et al. Vasc Health Risk Manag 2010;6:541–8; 6Whitmer RA et al. JAMA
2009;301:1565–72;
7McEwan P et al. Diabetes Obes Metab 2010;12:431–6
The consequences of hypoglycaemia
Hypoglycaemia
Cardiovascular
complications3
Weight gain by
defensive eating5
Coma3
Increased risk
of dementia6
Hospitalization
costs4
Loss of
consciousness3
Increased risk
of seizures3
Death2,3
Increased risk
of car accident1
Reduced
quality of life7
31

32. Ramadan Guidelines for patient with
Type I Diabetes mellitus
Very High Risk :
• Brittle DM.
• Patients on insulin pump
• Patients on multiple insulin injections per day
• Ketoacidosis or severe hypoglycaemia
• Advance micro vascular or macro vascular complication.

33. Consensus From
International Meetings On Fasting
TYPE 1 DIABETES
• Do not have to fast
• If insistent on fasting require very careful supervision if on
Basal Bolus. (Someone experienced and knowledgeable in
Diabetes Management.)

34. Fast with risk
• Well controlled DM
• No DKA
• No Recent hypoglycemia
• Not more than 2 injections per day

35. Ramadan guidelines for Type 2 DM
Very high risk:
• Severe hypoglycemia within the Last 3 months prior to Ramadan
patient with a history of recurrent hypoglycemia.
• Patient with hypoglycemia unawareness/alertness problem.
• Patient with sustained poor glycemic control .
• Ketoacidosis within the last 3 months prior to Ramadan.
• Hyperosmolar hyperglycemic coma within the last 3 months prior to
Ramadan & Acute illness.
• Patient on dialysis.

36. High Risk:
• Patient with renal insufficiency
• Patient with advance macrovascular complications -
Coronary, cerebrovascular & severe retinopathy
• Autonomic neuropathy- Gastro paresis and postural
hypotension
• Patient living alone and treated with multiple insulin
injection or sulfonylureas.
• Old age with ill health.
Ramadan guidelines for Type 2 DM

37. Categories of risks in patients with type 1 or type
2 diabetes who fast during Ramadan
(ADA Position Statement on Ramadan )
Moderate risk
• Well-controlled patients treated with short-acting insulin,
secretagogues such as repaglinide or nateglinide
Low risk
• Well-controlled patients treated with diet alone, metformin, or a
thiazolidinedione who are otherwise healthy
Physiological condition:
• Pregnancy, Lactation

38. Co-existing major medical conditions
• Acute peptic ulcer,
• Severe bronchial asthma, Pulmonary Tuberculosis,
• Cancer
• Overt cardiovascular diseases-
- Recent MI, Sustained angina.
• Hepatic dysfunction.

39. Guideline for Ramadan
Educational Counseling
• Plan at least 3 months before
• Education of diabetic patients and their families
• Must focus on:
- The situations contraindicating fasting
- Treatment of diabetes and it’s modification: *Meal planning
*physical activities *medication
- Importance and tool of self monitoring skills and adjustment
• Must insist on:
- The risk of acute complication and means to prevent
them

40. Lifestyle management:
Physical activity : exercise
1. Reduce physical activities during the day
2. Physical exercise can be performed about one hour after
Iftaar.
3. Taraweih prayer should be considered a part of daily exercise
program.

41. Dietary assessment: Nutrition
• Ensure adequate hydration and electrolyte
• No significant difference, from a healthy and balanced diet.
• Take sahur close to predawn time.
• Change in the schedule, amount and composition of meals
according to individual choice.
• Plan the diet chart considering carb counting according to
patient habit and social customs.
• Keep the daily total calorie same, divide into 2/3 schedule
according to choice and tradition

42. Dietary guidelines:
• Divide your food in to 2-3 meal –
- Iftaar, Dinner & Sahur/predawn.
• Limit the amount of sweet food taken at iftaar –
- Jelapi, laddoo, burfi, sweets, sugar containing sarbat
• Limit fried food-
- Samosas , pakoras, puri, parata, fried kababs.
• Choose sugar free type drinks and drink plenty water. Use sugar free
sweetner where needed-Canderal, Equal, Sweetex
• Fill up on starchy food during-Dinner and Sahur –rice, capati, nan,
vegetables, dhal, fish, meat, geg, milk, yoghurt and fruits.

43. Before Ramadan During Ramadan
• IdegAsp insulin twice daily, e.g., 30
units in morning and 20 units in
evening
• Use the usual morning dose at the
sunset meal (Iftaar) and half the
usual evening dose at predawn
(Sahur), e.g. IdegAsp insulin, 30
units in evening and 10 units in
morning.
Recommended changes to treatment regimen in
patients with type 2 diabetes who fast during
Ramadan
(ADA Position Statement on Ramadan )
• Patients’ on Ryzodeg®

44. Consensus From International Meetings On
Fasting
If on IdegAsp+ Metformin
• Give Iftaar (evening dose) as same as for breakfast
premixed dose but
• Take Metformin at Sahur (early morning meal) and Iftaar and
patient may be okay and may not require premixed at Sahur
• But if midday blood sugar control not good, add premixed
50% of normal evening dose at Sahur (early morning meal)

45. Before Ramadan
IdegAsp 30/70 twice
daily
Morning Dinner
30 U 20 U
During Ramadan
Iftaar Dinner Sahur
M 30-full dose 0 D 10- ½ dose
Ryzodeg®dosing
Patient on insulin

46. Monitoring during Ramadan
• Blood glucose level during the fast
- to recognize subclinical hypo and hyperglycemia.
• 2hour post Sahur and one/two hour pre Iftaar
- to pick subclinical hypoglycemia.
• 2 hour post Iftar/ Dinner
- to pick sub clinical hyperglycemia
Adjust insulin dose 3 days interval
Pre-iftaar- Adjust Detemir/Glagine
Mid day-Adjust NPH
2 h Post iftaar-Adjust iftar aspart
2 h Post dinner- Adjust dinner aspart
2 h Post sahur-Adjust sahur aspart

47. Monitoring during Ramadan
• If blood glucose is noted to be low, the fast must be broken.
• If blood glucose > 300 mg /dl or, 16.66 m.mol/dl,
- ketones in urine should be checked.

48. Consensus From International Meetings On
Fasting
Monitoring
• Finger stick BG after Iftaar and before sahur
• BG if feeling bad (low)
• Terminate fast if BS below 60 mg/dl or over 400 mg/dl
• No exercise before Iftaar
• Drink plenty of water at iftaar and Sahur

49. 49
Hypoglycaemia continues to be a main obstacle for
HCPs to effectively treat with insulin
Results from the GAPP™ study
GAPP™
• A global internet survey of patient and
physician beliefs regarding insulin therapy
• n=1250 physicians
GAPP, Global Attitudes of Patients and Physicians; HCP, health care provider
Peyrot et al. Diabetic Med 2012;29:682–9
72%
79%
0 20 40 60 80 100
Percentage
I would treat my patients more
aggressively if there was no
concern about hypoglycaemia
p<0.05
Diabetes specialistsPrimary care physicians

50. Fear of hypoglycaemia reduces patient adherence and
may affect glycaemic control
Many patients decrease their insulin dose
following a hypoglycaemic event
74%
79%
43%
58%
0%
20%
40%
60%
80%
100%
Non-severe episodes Severe episodes
Patients
modifying insulin
dose
Type 1 diabetes
Type 2 diabetes
Total patient sample, n=335 (type 1 diabetes, n=202; type 2 diabetes, n=133)
Leiter et al. Can J Diabetes 2005;29:186–92

51. 51
Hypoglycaemia is a problem with diabetes therapy
0%
5%
10%
15%
20%
25%
30%
35%
0
5,000
10,000
15,000
20,000
25,000
30,000
35,000
Percentageofestimated
numberofhospitalisations
Estimatednumberof
hospitalisations
95% of all endocrine emergency hospitalisations
in people >65 years are caused by hypoglycaemia
Medications most commonly associated with emergency hospitalisation
Data given are number and percentage of annual national estimates of hospitalisations. Data from the NEISS-CADES project.
ER visits n=265,802/Total cases n=12,666. ER, emergency room
Budnitz et al. N Engl J Med 2011;365:2002–12

52. 52
52
Presentation title Date

53. 53
Patient might get confused to manage diabetes during Ramadan
53
Presentation title Date

55. Novo Nordisk® introduces
A novel co-formulation insulin analogue
for managing Diabetes Mellitus

56. BOOST: INTENSIFY PREMIX I
Hypoglycaemia
SAS. Comparisons: Estimates adjusted for multiple covariates
Severe hypoglycaemia occured in 3.1% (7/224) of patients on IDegAsp (rate 0.09 episodes/PYE) compared to 7.2% (13/222) of patients on BIAsp 30 (rate 0.25
episodes/PYE), IDegAsp vs. BIAsp 30 rate ratio: 0.50
Fulcher et al. IDF 2013. Poster P-1399
73% lower
rate with
IDegAsp,
p<0.0001
32%
lower rate
with
IDegAsp,
p=0.0049
Time (weeks)
0
1
2
3
4
5
6
7
8
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Confirmedhypoglycaemia
(cumulativeeventsperpatient)
Overall confirmed
hypoglycaemia
Confirmed nocturnal
hypoglycaemia
IDegAsp BID (n=224)
BIAsp30 BID (n=222)
0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Nocturnalconfirmed
hypoglycaemia
(cumulativeeventsperpatient)
Time (weeks)

57. BOOST: INTENSIFY ALL
Hypoglycaemia
SAS. Comparisons: Estimates adjusted for multiple covariates
Severe hypoglycaemia occured in 1.4% (4/279) of patients on IDegAsp (rate 0.05 episodes/PYE) compared to 1.4% (2/141) of patients on BIAsp 30 (rate 0.03 episodes/PYE)
Christiansen et al. IDF 2013. Poster P-1395
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Confirmedhypoglycaemia
(cumulativeeventsperpatient)
Similar
estimated rate
in the 2 trial
arms (ns)
Time (weeks)
Confirmed hypoglycaemia
33% lower
rate with
IDegAsp (ns)
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0 2 4 6 8 10 12 14 16 18 20 22 24 26
Nocturnalconfirmedhypoglycaemia
(cumulativeeventsperpatient)
Time (weeks)
Confirmed nocturnal
hypoglycaemia
IDegAsp BID (n=279)
BIAsp30 BID (n=141)

58. 1.28%
HbA1c
Reduction
Treatment difference:
Non-inferior
Ryzodeg® successfully achieved HbA1c
reductions in a multinational study…13,14
Mean HbA1c vs BIAsp 30 in a type 2 diabetes study13,14
6.5
7.0
8.0
HbA1c(%)
0
0 2 4 6 8 10 12 14 16 18 20 22 24
BIAsp 30 BID
Ryzodeg® BID
7.5
8.5
9.0
7.1%
26
Time (weeks)
In a type 2 diabetes study
• Similar reductions in HbA1c vs. BIAsp30 BID as expected in treat-to-target study14
Ref.: 13. Ryzodeg® [summary of product characteristics]. Bagsværd, Denmark: Novo Nordisk
A/S; 2014. 14. Fulcher G, Christiansen JS, Bantwal G, et al; on behalf of the BOOST: Intensify
Premix I Investigators. Comparison of insulin degludec/insulin aspart and biphasic insulin
aspart 30 in uncontrolled, insulin-treated type 2 diabetes: a phase 3a, randomized, treat-to-
target trial. Diabetes Care. 2014;37(8):
2084–2090.