Post on 29-Jan-2018
Riwayat Hidup :
• Nama : Dr Eddy Supriadi, Sp.PD, FINASIM
• Tempat/ Tgl. Lahir : Jakarta, 19 Feb 1968
• Pendidikan : Dokter, FKUI 1993, Penyakit Dalam FKUI 2006
• Tempat Kerja : RS Dr H. MARZOEKI MAHDI KOTA BOGOR
• Pengalaman :
- Inspire Diabetes Program. PERKENI Indonesia-STENO Denmark. Jakarta 2013.
- Workshop and Symposium on the Diabetic Foot. Noordwijkerhout, The Netherlands, 2011
- dll.
Slide no 1
Insulin intensification : the usage of premixed insulin after basal fails
EDDY SUPRIADI, MD.MARZOEKI MAHDI , MD. HOSPITAL.BOGOR
OutlinesPresentation structure
• What recent guideline say
• Addresing post prandial glucose excursion
• Minimising hypoglycaemia
• A1chieve observational study: real life experience including Indonesia
• Insulin Intensification : how simple ?
• Conclusion
1. Fonseca. Br J Diab Vasc Dis 2008;8(Suppl 2):S3; 2. Holman et al. N Engl J Med 2007;357:1716–30; 3. Inzucchi et al. Diabetologia 2012;55:1577–96.. 4. Garber AJ, et al. Diabetes, Obesity and Metabolism, 8, 2006, 58–66
The ADA/EASD have found that basal plus two or more
bolus injections is a highly complex regimen3
4
• Type 2 diabetes progression is characterised by a decline in ß-cell function and worsening insulin resistance1
• Within 1 year, the majority of basal insulin patients will need another insulin to reach target2
• Premix Insulin offer a simple intensification of one insulin in one device4
Background
Slide 5
Type 2 diabetes is a progressive disease
Lebovitz. Diabetes Reviews 1999;7:139–53 (data are from the UKPDS population: UKPDS 16. Diabetes 1995;44:1249–58)
HOMA: homeostasis model assessment
ADA/EASD Position on Sequential Insulin Strategy in Type 2 Diabetes
Non-Insulin Regimes
Basal Insulin OnlyUsually with OAD
Basal Insulin + 1 mealtime rapid-acting injection
Pre-mixed Insulin twice-daily
Basal Insulin + >2 mealtime rapid-acting injection
1
2
+3
Low
Mod.
High
Number of Injections
Regimen Complexity
FlexibilityLess FlexibleMore Flexible
Convenience*More ConvenientLess Convenient
Inzucci SE, et al. Diabetologia. 2012. * Gumprecht et al. Intensification to to biphasic insulin aspart 30/70. Int J Clin Pract 2009
Lifestyle measuresIf not at target (generally HbA1c <7%)
1. Adapted from the IDF Treatment algorithm for people with type 2 diabetes. Accessed at: http://www.idf.org/treatment-algorithm-people-type-2-diabetes (accessed May 2012)
treatments that can help to address PPG are included at every stage of the IDF treatment algorithm1
• Sulphonylurea
Second line
• Metformin• a-glucosidase
inhibitor• DPP-4 inhibitor• Thiazolidinedione
• Premix insulin• Basal insulin• Basal-bolus insulin
Fourth line:insulin intensification
• Premix insulin• Basal insulin• a-glucosidase inhibitor• DPP-4 inhibitor• Thiazolidinedione
Third line:insulin start
• GLP-1 agonist
First line
• Metformin
• Sulphonylurea• a-glucosidase
inhibitor
IDF recommends premix or basal insulin at start
and intensification
Standard approach
Alternative approach
7
APROM ID# 5069 approval date: May 2013
OutlinesPresentation structure
• What recent guideline say
• Addresing post prandial glucose excursion
• Minimising hypoglycaemia
• A1chieve observational study: real life experience including Indonesia
• Insulin Intensification : how simple ?
• Conclusion
Treatment therapies for Type 2 diabetes: Achieving HbA1c < 7%
Adapted from Raccah et al. Diabetes Metab Res Rev 2007;23:257.
Lifestyle + Metformin
+-other OAD or GLP-1 agonists
Basal Insulin
(Once-daily treat-to-target)
PremixedInsulin
(Twice dailyTreat to target)
Basal Insulin
(Basal + 1 or 2 prandial)
Basal Insulin
(Basal + 3 prandial)
HbA1c ≥7.0% HbA1c ≥7.0%, FPG on target, PPG ≥160 mg/dl
Every 1% drop in HbA1c can reduce long-term diabetes
complications1
37%
Microvascular complications*
21%
Deaths relatedto diabetes*
14%
Myocardialinfarction*
*p<0.0001. 1. Adapted from Stratton et al. BMJ 2000;321:405–12 (UKPDS 35)
10
Slide 11
The benefits of good blood glucose control are clear
Good control is ≤ 7.0% HbA1c
HbA1c measures the average blood glucose level over thelast three months
Source: UKPDS = United Kingdom Prospective Diabetes Study. Stratton IM et al. BMJ. 2000;321(7258):405-412.
Deaths related to diabetes
Microvascular complications
Myocardial infarction
-14%
-37%
-21%
HbA1c
-1%
Yet good glycaemic control is not achieved
Adapted from Unger et al. Am J Med 2008;121:S3–S8.
12.4% have HbA1c>10.0 %
20.2% have HbA1c>9.0 %
37.2% have HbA1c>8.0 %
HbA1c (%)
10.0
9.5
9.0
8.5
8.0
7.5
7.0
6.5
6.0
5.5
64.2% of patients with type 2 diabetes have HbA1c≥7.0 %
PPG control is vital to achieving HbA1c targets1
1. Adapted from Monnier et al. Diabetes Care 2003;26:881–5
Rela
tive c
on
trib
uti
on
to
o
verall h
yp
erg
lycaem
ia(%
)
HbA1c quintiles
0
20
40
60
80
100
<7.3 7.3–8.4 8.5–9.2 9.3–10.2 >10.2
to overall hyperglycaemia as patients approach HbA1c
targets1
PPG has an
FPG PPG
APROM ID# 5069 approval date: May 2013
13
Patients spend 50% of their day in the postprandial state1
1. Adapted from Monnier. Eur J Clin Invest 2000;30(Suppl. 2):3–11
4 h4 h
4 h
MIDNIGHT
6 PM
Breakfast
Evening meal
Lunch
6 AM
MID-DAY
Fasting state
Postprandial state
14
Is postprandial hyperglycaemia harmful?
Postprandial hyperglycaemia is harmful, and should be addressed
• Postprandial hyperglycaemia are independent risk factors for macrovascular disease
• Postprandial hyperglycaemia is associated with:
• Increased risk of retinopathy, increased CIMT, decreased myocardial blood volume/blood flow, increased risk of cancer, impaired cognitive function in the elderly
• Postprandial hyperglycaemia causes oxidative stress, inflammation and endothelial dysfunction
IDF Recommendation:
Physiological insulin
profile:
• Basal component
• Meal-related peaks
The dual-release insulin concept: Premix Insulin
targets both FPG and PPG1
1. Garber et al. Diabetes Obes Metab 2006;8:58–66; 2. Garber et al. Diabetes Obes Metab 2007;9:630–9
Basal insulin
BiAsp 30
Physiological insulin profile
Time
Pla
sm
a insulin level
APROM ID# 5069 approval date: May 2013
Adapted from Garber2
16
The IMPROVE™ study - reduced FPG and PPG with BiAsp 301
*p<0.001
1. Adapted from Valensi et al. Int J Clin Pract 2009;63:522–31
Pre-breakfast FPG Post-dinner PPG
Baseline Week 26
FPG and PPG from baseline at Week 26 following initiation or switch to BiAsp301
14
12
10
8
6
4
2
0
10.9
6.6
12.6
7.9
Blo
od
glu
co
se
(mm
ol/
L)
APROM ID# 5069 approval date: May 2013
1 1
17
INITiation of Insulin to reach A1c TargEt (INITIATE): BIAsp 30 (BID) vs. glargine (OD)
n=233Type 2 diabetesBMI <40 kg/m2
Body weight <125 kgHbA1c >8%on metformin ± TZD
Insulin glargine OD (12 U, bedtime) + metformin ± pioglitazone
BIAsp 30, pre-breakfast (6 U) and pre-dinner (6 U) + metformin ± pioglitazone
4-week run-in:Stop insulin secretagogues (SUs, nateglinide, repaglinide) and -glucosidase inhibitors (acarbose)Optimise metformin to ≥1500 mg/daySwitch rosiglitazone for 30 mg pioglitazone
–4 0 28Time (weeks)
SUs, sulphonylureasRaskin et al. Diabetes Care 2005;28(2):260–5
BIAsp 30 (n=100)Insulin glargine (n=109)
66%
42%40%
28%
0
10
20
30
40
50
60
70
HbA1c <7.0% (ADA goal)
HbA1c ≤6.5% (ACE and IDF goal)
HbA1c target
Pati
ents
rea
chin
g ta
rget
at W
eek
28
(%
)p=0.0002
p=0.0356
INITIATE: significantly more patients met HbA1c targets with BIAsp 30
Raskin et al. Diabetes Care 2005;28(2):260–5
Dif
fere
nce
in p
ran
dia
l glu
cose
in
crem
ent
bet
wee
n t
reat
men
ts
(mm
ol/
L)
Total meanprandial glucose
increment
Favours glargine
Favours BIAsp 30
Breakfast
–1.17
0.66
–1.25
–0.59
**
ns
*
*
*p<0.05**p<0.01
–2.5
–2.0
–1.5
–1.0
–0.5
0.0
0.5
1.0
INITIATE: improved control of PPG with BIAsp 30
ns, not significant
Lunch Dinner
Raskin et al. Diabetes Care 2005;28(2):260–5
OutlinesPresentation structure
• What recent guideline say
• Addresing post prandial glucose excursion
• Minimising hypoglycaemia
• A1chieve observational study: real life experience including Indonesia
• Insulin Intensification : how simple ?
• Conclusion
A well-documented tolerability profile
* PubMed search using term ‘biphasic insulin aspart’ and the limit ‘randomised controlled trial’. 1. Sharma et al. Curr Med Res Opin 2008;24:645–52; 2. Almustafa et al. Diabetes Res Clin Pract 2008;81(Suppl. 1):S10–5; 3. Güler et al. Arch Drug Inf 2009;2:23–33; 4. Valensi et al. Int J Clin Pract 2009;63:522–31; 5. Wenying et al. Curr Med Res Opin 2009;25:2643–54; 6. Gumprecht et al. Int J Clin Pract 2009;63:966–72; 7. Home et al. Diabetes Res Clin Pract 2011;94:352–63; 8. El Naggar et al. Diabetes Res Clin Pract 2012;98:408–13
2002–2012In at least 68 BiAsp 30 RCTs*
2007–10 PRESENT observational study1–3
>22,000 patients
2008–2012 IMPROVE™ observational study4–6
>51,000 patients
2010–2012A1chieve®
observational study7,8
>66,000 patients
of clinical experience*1–8
BiAsp 30 tolerability profile demonstrated over
22
Hypoglycaemia following intensification from basal
insulin analogue to BiAsp 301
1. Adapted from Gumprecht et al. Int J Clin Pract 2009;62:1809–19
Baseline Final visit
in the rate of hypoglycaemia following intensification to BiAsp 301Hypoglycaemia
8
6
4
2
0Even
ts/
pati
en
t year
0.197
Major
0.016
7.8
6.1
Minor
APROM ID# 5069 approval date: May 2013
23
10
OutlinesPresentation structure
• What recent guideline say
• Addresing post prandial glucose excursion
• Minimising hypoglycaemia
• A1chieve observational study: real life experience including Indonesia
• Insulin Intensification : how simple ?
• Conclusion
Presentation title Slide no 26Date
Role of observational studies and RCTs
Observational studies . . .
" . . . complement (the data) from RCTs by
providing an insight into how treatments perform
in day-to-day practice in more clinically
representative patient populations ”
Home, Diabetes Res Clin Pract, 2010
Presentation title Slide no 27Date
Strengths of observational studies
1. Yang et al Diabetes Res Clin Pract, 2010 2. Home Diabetes Res Clin Pract, 2010 3. Dreyer et al Health Affairs 2010
• Observational study of people with T2DM in routine clinical practice
• Study objectives• Primary: number of attributed adverse drug reactions
(includes major hypoglycaemia)
• Secondary: other safety and effectiveness measures
BASELINEWeek 0
INTERIMWeek 12
FINALWeek 24
Start a study insulin
• Biphasic insulin aspart 30
• Insulin detemir• Insulin aspart
A1chieve study overview and design
BiAsp 30± OAD: Indonesia efficacy results Insulin users
HbA1c (%) FPG (mg/dl) PPG (mg/dl)
Baseline values 10.0 9.4 232 204 303 278
n 385 92 769 383 752 328
*p<0.001
-2.1*
-3,0
-2,0
-1,0
0,0
Cha
nge
from
bas
elin
e to
w
eek
24
-72*
-110*
-150
-130
-110
-90
-70
-50
-30
-10
BiAsp 30± OAD: Indonesia hypoglycaemia results
1.64
0.00
0.51
0.03 0.00 0.00 0.0
1.0
2.0
3.0
Overall Major Nocturnal
Insulin users Insulin users Insulin users
No. of pt w/hypo 29 1 0 0 16 0
Events
/patient-
year
Baseline
24 weeks
A1chieve: Self-rated health in insulin users (BiAsp 30)
24 weeks
Baseline
Best imaginable health
Worst imaginable health0
10
20
30
40
50
60
70
80
90
100
Baseline 24 weeks
Patients on BiAsp 30
BiAsp 30: real world
improvement in patients
quality of life
A1chieve study overall summary
• Significant HbA1c, FPG and PPG reductions for BiAsp
• 2.1% HbA1c reduction in insulin users
• Indonesian patients reported a reduction in hypoglycaemia during treatment with BiAsp at 24 weeks in term of:
• Minor
• Major
• Nocturnal
• Patient quality of life increased significantly with BiAsp following 24 weeks of treatment
OutlinesPresentation structure
• What recent guideline say
• Addresing post prandial glucose excursion
• Minimising hypoglycaemia
• A1chieve observational study: real life experience including Indonesia
• Insulin Intensification : how simple?
• Conclusion
How do we define insulin intensification?
Modification of the insulin regimen, e.g. adding to or changing the therapy in order to maintain glycaemic control
INTENSIFY
Starting insulin therapy
Dose titration to ensure that the patient receives the maximum benefit from the prescribed treatment
OPTIMISE
INITIATE
Slide 35
Basic Insulin Start Recommendation
If Fasting Blood Glucose is elevated • Start with Basal Insulin
If both Fasting and Prandial Blood Glucose are elevated
• Start with Premix Insulin• OR add Basal Insulin to OAD
• OR Start Basal/Bolus Therapy
Source: ADA Guidelines
Insulin Treatment OptimizationHow to Optimize Treatment with Pre-mix
Basal Once-DailyUsually with OAD
Start with basal 10u / day and titrate accordingly if glycemic target is not reached.
Pre-mix Twice-DailyUsually with OAD
Source: PERKENI Insulin Guidelines 2011
Pre-mix Thrice-DailyUsually with OAD
Switch to Pre-mix twice-daily ifglycemic target is not reached.Initially keep the dose equalfrom basal but split it in halfand inject at morning anddinner time. If high bloodglucose before evening mealincrease morning dose of pre-mix and if high fasting Bloodglucose increase evening dosepre-mix.
Switch to Pre-mix thrice-daily if glycemic target isnot reached. Add 2-6 unit or10% of daily dose to thetotal dose and inject atlunch. Reduce morning dosewith 2-4 units after staringlunch time injections
Practical guideline on intensification of insulin therapy with BIAsp 30
A simple algorithm for the intensification of basal insulin OD or BiD to BIAsp 30 BID
Basal insulin OD or BID
Switch to BIAsp 30 BID
HbA1c 7-8%
Titrate basal insulin to achieveFPG <110 mg/dl
FPG >110 mg/dl FPG: 73-110 mg/dl
HbA1c >8%
1. Adapted from Unnikrishnan et al. Int J Clin Pract 2009;63:1571–7
Intensifying basal insulin patients to Premix
is simple
• BiAsp 30 can be intensified to three-times daily* to achieve glycaemic control2
• The morning dose can be split into morning and lunchtime doses for three-times-daily dosing3
• BIAsp 30 TID: alternative to basal-bolus (fewer daily injection and only one device need)
*Guideline for the recommended dose adjustment included in the NovoMix® 30 SmPC3. 1. Unnikrishnan et al. Int J of Clin Prac 2009; 63:1571–7; 2. Garber et al. Diabetes Obes Metab 2006;8:58–66; 3. Novo Nordisk. NovoMix® 30 summary of product characteristics
Adapted from Unnikrishan1
Breakfast Dinner
Split total daily dose 50% 50%
In basal insulin patients: start with the same total daily dose1
unitbasal insulin
Intensify to
unitBiAsp 30
38
Twice daily BiAsp 30
Adjusting the dose of BiAsp 30
1. Novo Nordisk. NovoMix® 30 summary of product characteristics. May 2012
Adapted from NovoMix® 30 SmPC1
Pre-meal bloodglucose level
mg/dL
BiAsp 30dose adjustment
Units
<80 -2
80–110 0
111–140 +2
>180 +6
141–180 +4
Recommended dose adjustments
39
OutlinesPresentation structure
• What recent guideline say
• Addresing post prandial glucose excursion
• Minimising hypoglycaemia
• A1chieve observational study: real life experience including Indonesia
• Insulin Intensification : how simple?
• Conclusion
Conclusion
• Because of the progessiveness of diabetes, Insulin regimen and dosage needs to be monitored and intensified
• BiAsp 30 provides effective glycaemic control with significant HbA1c
reduction, FPG and PPG reduction with additional convenience for patients
• In Indonesia, in a real life clinical practice, A1chieve study results for BiAsp 30 show significant improvements in overall glycaemic control in terms of HbA1c, FPG and PPG, reductions in hypoglycemia and a significant improvement in patient quality of life
Thank You