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Insulin degludec/insulin aspart-an overview of co-formulation insulin
analogue and use in Ramadan
Dr Shahjada Selim Assistant Professor
Department of EndocrinologyBangabandhu Sheikh Mujib Medical University, Dhaka
Presentation title Date 1
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
Diabetes: Facts and figures
Almost half of all people with diabetes live in just three countries
ChinaIndian 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
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
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
Progressive treatment should follow progressive disease
7
Type 2 diabetes is a progressive disease
HOMA, homeostasis model assessmentAdapted from: UKPDS 16. Diabetes 1995;44:1249–58
8
3049 55 60 70
7051 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
Contr
ibuti
on t
o o
vera
llhyperg
lyca
em
ia (
%)
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 glucose1. Monnier et al. Diabetes Care 2003;26:881-5; 2. Swinnen et al Diabetes Care 2009;32 (Suppl. 2):S253-9
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
Pla
sma Insu
lin(μ
U/m
L)
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
Insulin optimisation and intensification should follow disease progression
Beta
cell
funct
ion
(%
)
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
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
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;16:323. 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…
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
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
• 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
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-d
ay v
ari
ab
ility
(coeffi
cien
t of
vari
ati
on
%)
Variability in glucose-lowering effect over 24 hours at steady state3
IDeg variability is four-fold lower than IGlar
54320 1 6Days since first dose
IDeg
seru
m c
on
cen
trati
on
Prop
ort
ion
of
Day 6
level (%
)
0
Type 2 diabetes
0 1 2 3 4Prop
ort
ion
of
Day 4
level
(%)
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
IDegAspA soluble co-formulation of insulin degludec and insulin aspart
Havelund et al. Pharm Res 2015 Jan 8 [Epub ahead of print]
IAsphexamers
Phenol1
IDegdihexamers
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
Ryzodeg® 0.3 U/kg BIDInjections
The flat and stablebasal coverage beyond 24 hours of insulin degludec
Time (in hours)
Glu
cose
in
fusi
on
rate
(m
g/k
g*m
in)
in t
yp
e 1
pati
en
ts
The mealtime control of insulin aspart
8
6
4
2
00 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
IDegAsp shows distinct prandial and basal glucose lowering effects compared with BIAsp30
n=22 for IDegAsp; n=24 for BIAsp 30T1DM, type 1 diabetes1. 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
Glu
cose
in
fusi
on
rate
(m
g/(
[kg
•m
in])
4 8 12 16
8
6
4
0
2
Time since injection (hours)
20 24
Glu
cose
in
fusi
on
rate
(m
g/[
kg
•m
in])
Time since injection (hours)
BIAsp 30 (single dose)210
0 4 8 12 16
8
6
4
0
2
20 24
Shoulder effect
21Results from studies NN2004-1418 and NN5401-1959 in patients with T1DM
Profile: IDegAsp vs BIAsp 30 & BHI30
BHI 30IDegAsp
11Nominal 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
Glu
cose
infu
sion r
ate
(m
g/k
g/m
in)
0
1
2
3
4
5
6
7
8
9
10
BIAsp 30
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
NormalRenal function group
MildModerateSevere
Creatinine clearance (mL/min)10 100 1000
AU
CID
eg
,0–1
20
h,S
D
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
00
4 8 12 16 20 24
2000400060008000
10000
Renal function groupNormalMildModerateSevere
Hepatic function groupNormalChild–Pugh AChild–Pugh BChild–Pugh C
Time since injection (hours)
00
4 8 12 16 20 24
2000400060008000
10000In
sulin
deg
lud
ec
seru
m c
on
cen
trati
on
(p
mol/L)
00
4 8 12 16 20 24
2000400060008000
10000
IDeg 0.4 U/kg
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 requirementsIDegAsp 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
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
1:1OD
Basal/Premix IDegAsp
BID
1:1≥BID
Basal/Premix IDegAsp
Dosing of IDegAsp: Transfer fromother insulins
Ryzodeg® Summary of Product Characteristics 2013
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 meal1. Fulcher et al. IDF 2013. Poster P-1399; 2. Christiansen et al. IDF 2013. Poster P-1395
Ramadan Guidelines for Patients with Diabetes Mellitus
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.
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
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; 9McEwan P et al. Diabetes Obes Metab 2010;12:431–6
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
Cardiovascularcomplications3
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
Ramadan Guidelines for patient withType 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.
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.)
Fast with risk
• Well controlled DM • No DKA• No Recent hypoglycemia • Not more than 2 injections per day
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.
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
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 nateglinideLow risk• Well-controlled patients treated with diet alone, metformin, or a
thiazolidinedione who are otherwise healthyPhysiological condition: • Pregnancy, Lactation
Co-existing major medical conditions
• Acute peptic ulcer,• Severe bronchial asthma, Pulmonary Tuberculosis,• Cancer• Overt cardiovascular diseases- - Recent MI, Sustained angina.• Hepatic dysfunction.
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
Lifestyle management:
Physical activity : exercise
1. Reduce physical activities during the day2. Physical exercise can be performed about one hour after
Iftaar. 3. Taraweih prayer should be considered a part of daily exercise
program.
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
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.
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®
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)
Before Ramadan
IdegAsp 30/70 twice dailyMorning Dinner30 U 20 U
During Ramadan
Iftaar Dinner SahurM 30-full dose 0 D 10- ½ dose
Ryzodeg®dosing
Patient on insulin
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
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.
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
Hypoglycaemia continues to be a main obstacle for HCPs to effectively treat with insulinResults 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 providerPeyrot et al. Diabetic Med 2012;29:682–9
0 10 20 30 40 50 60 70 80 90 100
72%
79%
Percentage
I would treat my patients more aggressively if there was no
concern about hypoglycaemia
p<0.05
Diabetes specialistsPrimary care physicians
Fear of hypoglycaemia reduces patient adherence and may affect glycaemic control
Many patients decrease their insulin dose following a hypoglycaemic event
Non-severe episodes Severe episodes0%
20%
40%
60%
80%
100%
74%79%
43%
58%
Patients modify-ing insulin dose
Type 1 diabetesType 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
Hypoglycaemia is a problem with diabetes therapy
War
farin
Insu
lins
Oral a
ntip
late
let a
gent
s
OADs
Opiod
s
Antib
iotic
s
Digox
in
Antin
eopl
astic
age
nts
Antia
dren
ergi
c ag
ents
Reni
n-an
giot
ensin
inhi
bito
rs
Seda
tives
or h
ypno
tics
Antic
onvu
lsant
s
Diure
tics
0
5,000
10,000
15,000
20,000
25,000
30,000
35,000
0%
5%
10%
15%
20%
25%
30%
35%
Est
imate
d n
um
ber
of
hosp
italisa
tions
Perce
nta
ge o
f estim
ate
d
num
ber o
f hosp
italisa
tions
Opioi
ds
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 roomBudnitz et al. N Engl J Med 2011;365:2002–12
52
52Presentation title Date
53
Patient might get confused to manage diabetes during Ramadan
53Presentation title Date
Is there any solution?
Novo Nordisk® introduces
A novel co-formulation insulin analogue for managing Diabetes Mellitus
BOOST: INTENSIFY PREMIX I Hypoglycaemia
SAS. Comparisons: Estimates adjusted for multiple covariatesSevere 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 2 4 6 8 10 12 14 16 18 20 22 24 260
1
2
3
4
5
6
7
8
Confirm
ed h
ypogly
caem
ia
(cum
ula
tive e
vents
per
pati
ent)
Overall confirmed hypoglycaemia
Confirmed nocturnal hypoglycaemia
IDegAsp BID (n=224)
BIAsp30 BID (n=222)
0 2 4 6 8 10 12 14 16 18 20 22 24 260.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
Noctu
rnal con
firm
ed
hy-
pog
lycaem
ia
(cu
mu
lati
ve e
ven
ts p
er
pati
en
t)
Time (weeks)
BOOST: INTENSIFY ALLHypoglycaemia
SAS. Comparisons: Estimates adjusted for multiple covariatesSevere 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 2 4 6 8 10 12 14 16 18 20 22 24 260.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
Confirm
ed h
ypogly
caem
ia
(cum
ula
tive e
vents
per
pati
ent)
Similar estimated rate
in the 2 trial arms (ns)
Time (weeks)
Confirmed hypoglycaemia
33% lower rate with
IDegAsp (ns)
0 2 4 6 8 10 12 14 16 18 20 22 24 260.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
Noct
urn
al co
nfirm
ed h
ypogly
caem
ia
(cum
ula
tive e
vents
per
pati
ent)
Time (weeks)
Confirmed nocturnal hypoglycaemia
IDegAsp BID (n=279)
BIAsp30 BID (n=141)
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
Hb
A1
c(%
)
00 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.
The right choice of insulin therapy
during Holy Ramdan
