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Presentation title
Insulin Initiation :
When We should Start with Basal Insuli
Dr Ali Santosa SPPD
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AGENDA
Diabetes is a progressive disease and is increasing
in prevalence The mapping of insulin treatment based recent guidelines
Insulin Initiation, when we should start with basal insulin
Conclusion
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20102000171 million1
2030
552 millio
2011
366 million2
Diabetes is a global diseaseEstimated global prevalence of diabetes
1. Wild. Diabetes Care. 2004. 27:1047-1053.2. International Diabetes Federation.IDF Diabetes Atlas. Fifth Edition. 2011
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Normal
The progressive nature oftype 2 diabetes
Impairedglucosetolerance
Type 2diabetes
Fasting plasma glucose
Insulin sensitivityInsulin secretion
Insulinsensitive
Normal insulinsecretion
Normoglycaemia
Late type 2diabetescomplications
Adapted from Bailey CJ et al. Int J Cl
Groo LC. Diabetes Obes Meta
Insulin resistance
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Insulin and Glucagon Response to a LargeCarbohydrate Meal in Type 2 Diabetes
Insulin
(U/ml)
Glucagon
(g/ml)
Glucose
(mg/100
ml)
*Insulin measured in five patientsAdapted from Mller WA et al N Engl J Med1970;283:109115.
Type 2 diabetes mellitus (n=12)*Nondiabetic controls (n=11)
150
0140
90
360
80
240
60
Time (minutes)
306090
120
110
270300330
100110120130
Meal
Nonsuppressed glucagon
0 60 120 180
Depressed/delayed insulin respo
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100
75
50
25
UKPDS : Progressive Deterioration of -Cell Functio
Years from Diagnosis
Adapted fromLebovitz H. Diabetes Review 1999;7
BetaCellF
unction(%)
-12 10 -6 -2 0 2 6 10
Th/Expectation withintensive treatment
Facts
Why ?
ETIOLOGY OF BETA CELL FAILURE IN T2DM
Age5. Incretin
Effect
Genetic(TCF 7L2)
4. Amyloid
Deposition
1. Glucose
toxicity
2. Lipotoxicity
FFA
3. Insulin
Resistanc
Beta-cell
Failure
De Fronzo Banting Lecture (submitted ADA Meeting 2008 /Claude Bernard Awar
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-Cell Function Continues to Decline
Regardless of Intervention in T2DM
T2DM = type 2 diabetes mellitus
*-cell function measured by homeostasis model assessment (HOMA)
0
20
40
60
80
100
5 4 3 2 1 0 1 2 3 4
Years Since Diagnosis
-CellFunction(%)*
Progressive loss of -cell function
occurs prior to diagnosisMetformin
Diet (n = 1
Sulfonylur
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AGENDA
Diabetes is a progressive disease and is increasing
in prevalence The mapping of insulin treatment based recent guidelines
Insulin Initiation, when we should start with basal insulin
Conclusion
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Treat T2DM early for long-term benefits1
Long-term benefits in reducing cardiovascular risk can be achievgood control from diagnosis1
-14%
-37%
-21%
Myocardial infarction
Microvascular complic
Death related to diabe
Each HbA1cpercentage
point
reductioncounts3
HbA1c-1%
1. Holman, et al. NEJM 2008;359:1577892. UKPDS 6. Diabetes Res1990;13(1):1-113. Stratton, et al. BMJ2000;321(7258):405-12
50% of patients with T2DM with complicatalready have them at diagnosis2
http://images.google.dk/imgres?imgurl=http://www.buytaert.net/cache/images-miscellaneous-2006-eye-500x500.jpg&imgrefurl=http://buytaert.net/tag/photography?page=5&h=333&w=500&sz=200&hl=da&start=22&tbnid=XP6aV9751NDPgM:&tbnh=87&tbnw=130&prev=/images?q=eye&start=20&gbv=2&ndsp=20&svnum=10&hl=da&sa=Nhttp://images.google.dk/imgres?imgurl=http://www.barco.com/barcoview/downloads/BarcoVoxar3DCardia.jpg&imgrefurl=http://www.barco.com/corporate/en/pressreleases/show.asp?index=1662&h=680&w=680&sz=57&hl=da&start=7&tbnid=Arh6Yt46rdsIOM:&tbnh=139&tbnw=139&prev=/images?q=cardiac&gbv=2&svnum=10&hl=da8/11/2019 Levemir IDI UNMU 2014
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What is the optimal target HbA1clevel?
Goals of optimum HbA1clevels:
Good glycaemic control
Minimise development and progression of microvascularand macrovascular complications
HbA1c
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AGENDA
Diabetes is a progressive disease and is increasing
in prevalence The mapping of insulin treatment based recent guidelines
Insulin Initiation, when we should start with basal insulin
Conclusion
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Gaya hidup +
Metformin+Pioglitazon
Gaya hidup +
Metformin+
GLP-1 agonis
Gaya hidup +
Metformin+Pioglitazon +
sulfonilurea
Gaya hidup +
Metformin+
Insulin Basal
Less well validatedtherapies
Saat diagnosis:
Gaya hidup
+Metformin
Gaya hidup +
Metformin+
Insulin Basal
Gaya hidup +
Metformin+
SulfonilureaWell validated
therapies
Tahap 1 Tahap 2 ADA-EASD 2009
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Insulin remains the most efficacious glucoselowering agent
Decrease in HbA1c: Potency of monotherapy
HbA1c
%
Nathan et al., Diabetes Care 2009;32:193-203.
CHOOSING INSULIN EARLIERFOR BETTER EFFICACY
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Choosing Insulin
for your Patient?
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Insulin can be initiated anytim
Inadequate
Lifestyle+1 OAD
+2 OAD
+3 O
InitiateInsulin
Traditionally, insulin had been reserved as the last line o
Considering the benefits of normal glycemic status,
insulin can be initiated earlier, as soon as is required.
1. Fasting BG > 250 mg/dL
2. Random BG > 300 mg/d
3. Hb A1c > 10 %
4. Weight loss ++
5. Ketonuria
Indication:
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Once daily injection, anytime injection but in same time per each day
How to start basal insulin
Titrate the dose every3 days, if FPG >110mg/dl increased 3units and if FPG < 80mg/dl decrease 3units
Start with basalinsulin (InsulinDetemir) 10 U or 0,1-0,2 U per Kg BB
TitrateStart
Meneghini L et al. Diabetes Obes Metab, 9, 2007, 902-913
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How to titrate basal insulin
Levemir Dose Titration Guidelines:3-0-3 Algorithm
FPG>110 mg/dL + 3 U
80-110 mg/dL 0
FPG
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Levemirprovide optimal HbA1c reducti
Reference: 1. Soewondo P et al. Clinical experience with insulin detemir: Result from the Indonesian cohort of the international A1chieve study. Diabetes Res Clin Pract;suppl.S192013) S47-S53.
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Levemir reduces nocturnal hypoglycaemia by up65% compared to NPH
Phillis-Tsimikas. Clin Ther 2006;28(10):156981; Riddle et al 2003. Diabetes Care; 26 (11): 3080-
6; Asakura T et al, 2008. Expert Opin Pharmacother; 10 (9): 1-5; Hanel H et al 2008. J DiabetesSci Technol; 2 (3): 478-81
In
In
In
RelativeRisk
Riddleet al., 2003 Phillis-Tsimikas et al., 2006
-29% -44% -53% -65%
NPH vs. glargine NPH vs. detemir
Levemir Demonstrated More Consistent Insulin A
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LevemirDemonstrated More Consistent Insulin A54 Type 1 Diabetic Subjects Randomly Assigned to receive one type of Idose 0.4 u/kg, 4 Different Times
Adapted from Heise T et al. Diabetes. 2004;53:1614-20.
NPH NPH
Glargine Glargine
Detemir Detemir
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Levemir is approved in pregnancy and childrenyears
EMEA, FDA and BPOM has been approved Levemirin diabetes
(B category)and children 2 years
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Observational study of people with T2DM in
routine clinical practice
Study objectives Primary: number of attributed adreactions (includes major hypogly
Secondary: other safety and effemeasures
BASELINEWeek 0
INTERIMWeek 12
FW
Start a studyinsulin
Biphasic insulinaspart 30
Insulin detemir Insulin aspart
A1chieve study overview and desig
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HbA1c(%) FPG (mg/dl) PPG
Baseline values 9.5 219 263
n 147 317 295
Levemir OAD:Indonesia efficacy results
-101*
-
-120
-100
-80
-2.2*
-3.0
-2.0
-1.0
0.0
Changefromb
aselineto
week
24
*p
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Levemir OAD:Indonesia hypoglycaemia results
5,10
0,30
4,80
0,00 0,00 0,000,0
1,0
2,0
3,0
4,0
5,0
6,0
Overall Major Nocturnal
Insulin nave Insulin nave Insulin nave
No. of pt w/hypo 19 0 1 0 18 0
Percentwithatlea
stoneevent
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AGENDA
Diabetes is a progressive disease and is increasingin prevalence
The mapping of insulin treatment based recent guidelines
Insulin Initiation, when we should start with basal insulin
Conclusion
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The association between post cha
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The association between post-chaglycaemia and mortality
Adjusted for age, centre, sex, cholesterol, BMI, SBP, smoking
2.5
0
Hazardratio
formortality
2.0
1.5
1.0
0.5
2.5
0
2.0
1.5
1.0
0.5
>7.87-7.7
6.1-6.9
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Plasma Insulin
Normal 24 Hr Insulin Profiles & Bd prem
Bd premix Bd premix
NovoMix 30 provides better
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NovoMix 30 provides betterHbA1c reduction than Mixtard 30
65%
35%
30%
13.3%
0%
10%
20%
30%
40%
50%
60%
70%
ADA target (HbA1c < 7.0%) AACE target (HbA1c > 6.5%)
Proporti
onsachieving
HbA1ctar
gets
N
M
p
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Low risk of major hypoglycemia
Boehm et al. Eur J Interna
0
2
4
6
8
10
12
1st year 2nd year
Year of study
Patient
swithatleastonem
ajor
episode(%)
p= NS
p= 0.04
BIHu
5%
8%
0%
10%
Two Ye
Long-te
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Basal-Bolus Strategy as IdeConceptLevemir-Novorapid
Date
The Basal/Basal Plus strategy for T2DM
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Stepwise intensification of treatment for continuity o
Progressive deterioration of -cell function
Lifestyle changes
Oral agents
BasalAdd basal insulin and titra
Basal Add prandial insul
HbA1cabove target
FBG above target
HbA1cabove target
BAd
d
FBG at target
HbA1cabove target
Adapted from Raccah D, et al. Diabetes Metab Res Rev 2007 (in press).
Date
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Starting Basal-Bolus Program
In general
Calculate Total Daily Dose by using 0.5to Patient Body Weight (kg)
Example :
Patients Body weight : 60 kg
Total daily dose is : 0.5 x 60 kg : 30 iu
Use 60% of Total Daily Dose as Prandi(divided by 3) and 40% of TDD as Bas
PERKENI, Petunjuk praktis terapi insulin pada pasien DM, 2007
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Suntikkan 10 iu Levemir sekali sebelum tidur. Adosisnya (+3 atau 3) setiap 3 hari sd GDP men
Tambahkan Injeksi NovoRapid di setiap makan (2-
t k d lik G l d h 2 j PP
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Time of day (hours)
400
300
200
100
006.00 06.0010.00 14.00 18.00 22.00 02.00
Plasm
aglucose
(mg/dl)
NormalMeal Meal Meal
2
1
1
5
0
dosisnya (+3 atau -3) setiap 3 hari sd. GDP men
target GDP 80-110 mg/dL (Perkeni 2006)
Hyperglycaemia due to an increase in fasting glucose
T2DM
untuk mengendalikan Gula darah 2 jam PP menca
< 180 mg/dL (Perkeni 2006)BasalBolus Concept dengan Levemir -
NovoRapid
Profile T2
Conclusion
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Conclusion
Diabetes is a progressive disease that is increasing in prevalence world
Starting with basal insulin detemir is easy way to reach better glycontrol
In Indonesia, in real life clinical practice (A1chieve study) Levemisignificant improvements in overall glycaemic control in terms of and PPG.
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