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Insulin Glargine
(Lantus) & Insulin
Glulisine (Apidra) for
treatment of Diabetes
Patients
Insulin Glargine
(Lantus ):
The True Once Daily
24 hour
Basal Insulin
Analogue
-10
-5
Onset
10
15
Diagnosis
Insulin resistance
Insulin secretion
Impaired Fasting
Glucose
Post-Meal glucose
Fasting
glucose
Microvascular complications
Cardiovascular Complications
Pre-diabetes
Type 2 diabetes
Ramlo-Halsted BA, Edelman SV. Prim Care. 1999;26:771Nathan DM. N Engl J Med. 2002;347:1342-1
Stroke or TIA: 1%
NEWLY
DIABET
ES
Plasma creatinine
>120mol/l: 3%
Intermittent
Claudicasio: 3%
Foot skin ischemia : 6%
Retinopathy: 21%
Hypertension: 35%
Kumamoto
UKPDS
A1c
9% 7,2%
9% 7%
8% 7%
Retinopath
y
Nephropat
hy
63 %
69 %
54 %
70 %
17% 21%
24% 33%
Neuropath
y
CVD
60 %
improve
41 %
16%
50
Insulin
(U/mL) 25
Basal Insulin
0
Breakfast
150
Lunch
Dinner
Glucose
(mg/dL) 100
50
07
Basal Glucose
8 9 101112 1 2 3 4 5 6 7 8 9
AM
PM
Time of day
Adapted from Kruszynska Y et al. Diabetologia 1987;30:16.
Lunch
Dinner
Insulin (mU/L)
45
Physiological insulin
Ideal basal insulin
Ideal prandial insulin
30
15
0
06:00
12:00
18:00
Time
24:00
06:00
History !
100
80
30%
50%
55%
60%
45%
40%
60
40
70%
Basal
hyperglycemia
70%
50%
20
30%
Postprandial
hyperglycemia
0
<7.3
7.3-8.4
8.5-9.2
9.3-10.2
>10.2
A1c ranges (quintiles)
Postprandial hyperglycemia is most important except at high A1c
Monnier L et al. Diabetes Care 2003;26:881-885
Basal
hyperglycemia
Postprandial
hyperglycemia
<8.0
9.5
8.0-8.4
8.5-8.9
9.0-9.4
Baseline A1c ranges
On oral therapy, fasting hyperglycemia dominates over a wide range of A1c
20
T2DM
300
15
Hyperglycaemia due to an increase in fasting glucose
200
10
100
Normal
0
6
Meal
Meal
10
14
Meal
18
400
0
22
Basal Insulin
Once daily
(optimized)
OHA
mono or
combination
therapy
Diet and
exercise
HbA1c
uncontrolled
Basal Bolus
Basal Plus
Basal Plus
One prandial
for largest
glucose
excursion
Two prandial
for largest
glucose
excursion
Basal +
three prandial
Basal Insulin
akan berperan terhadap gula darah puasa
(fasting) & diantara makan (between meal)
24 hours
(Lantus)
Stabilit
y
Pergeseran titik
isolelektrik
Mikropresipitasi insulin
glargine dalam jaringan 3
Glargine (Lantus) :
Insulin Analog Kerja Panjang (Long Acting)
Insulin Glargine
(Lantus)
Peakless (Hampir
tanpa puncak)
Cairan jernih
Basal Insulin
Dapat diberikan
satu kali sehari
Tidak untuk
penggunaan IV
55%
Twice-daily
45%
Once-daily
Baseline
Study endpoint (after insulin glargine treatment)
TTT1
LANMET2
APOLLO3
4
LAPTOP
Triple
Therapy5 INITIATE6
1. Riddle M, et al. Diabetes Care 2003;26:30806. 2. Yki-Jrvinen H, et al. Diabetes Care 2006;49:44251.
3. Bretzel RG, et al. Lancet 2008;371:107384. 4. Janka H, et al. Diabetes Care 2005;28:2549.
5. Rosenstock J, et al. Diabetes Care 2006;29:5549. 6. Yki-Jrvinen H, et al. Diabetes Care
T2basal
bolus
T2-Lantus +
OADs
12months
24 weeks
24 weeks
(n=60) (n=206) p=0.0007 (n=367)
p<0.05 vs NPH
vs
NS vs NPH
conventional
therapy
44 weeks
(n=174)
NS vs 3 lispro
24 weeks
(n=58)
24
weeks
(n=273)
R
as
lo
va
T2Detemir
+ Bolus
H
aa
k
er
H
er
m
an
se
n
St
ud
y
13
37
St
ud
y
11
66
St
ud
y
13
73
Pi
eb
St
an
dl
T2-Detemir+OADs
Va
gu
e
an
se
n
er
H
er
m
Pi
eb
Le
eu
w
D
e
on
e
llJ
R
us
se
H
om
e
T1-basal bolus
9%
30%
Lantus
n=5,68
3
Detemir
N=694
P>0.05,
1. Currie CJ et al. Curr Med Res Opin 2007;23(Suppl 1): S33-S39
Type of hypoglycaemia
Insulin
glargine
NPH
(% of patients) (% of patients)
Risk
reduction
(%)
Nocturnal
PG 4.0 mmol/L (72 mg/dL)
PG 3.1 mmol/L (56 mg/dL)
23.9
16.3
33.9
23.1
<0.0001
<0.0001
29
29
Severe nocturnal
PG 4.0 mmol/L (72 mg/dL)
PG 3.1 mmol/L (56 mg/dL)
0.6
0.5
1.5
1.3
0.042
0.046
60
62
PG=plasma glucose
Rosenstock J, et al. Diabetes Care 2005;28:950-5.
35
*p<0.001;
p<0.012
Rosenstock J, et al. Diabetologia
Insulin
detemir
Low variability
39
Insulin Glulisine
(Apidra) :
A Unique Molecule & ZincFree
Glu+ Lys=
Gluisine
Insulin glulisine:
Substitution of asparagine B3
with lysine, and of lysine B29
with glutamic acid
A chain
Gly
B chain
20
Gln
Lys
Lys
Phe
=substitution
Cys
5
Ile
Asn
His
Gln
15
10
Glu
Glu
Ala
Pro
Lys
Thr
30
Phe
25
Gly
His
10
20
Leu
15
Qualitative composition
Human
mula unik dari insulin glulisine (Apidra)
Lispro
Aspart
Glulisine
Insulin
Components
Function
Glycerol (85%)
tonicity agent
---
Zinc
complexing agent
---
Polysorbate 20
stabilising agent
---
---
---
Kecepatan penyerapan
tergantung pada berat molekul
1.Becker RHA . Diabetes Ther & Tech 2007;9(1)109-21. 2. Hollemen F, et al. N Engl J Med 1997;337:17683
(adapted from Brange 1988)
Rapidacting
T
insulin
analogues:
Phenol
Insulin
lispro
Insulin
Structures
R-formatHexamers T-format
aspart
T T
Zn2+
Dimer
RapidNo added
acting
zinc
insulin
analogue: Polysorbate 20 (Tween 20)
Insulin
glulisine
Phenolic residues (
Capillary
ions ( )
Monomer
) Zn2+
Diabetes Ther & Tech 2007;9(1)109-21. 2. Hollemen F, et al. N Engl J Med 1997;337:17683
Insulin concentration
(mU/l)
200
150
N=18 non-diabetic
subjects; mean BMI: 34.7
kg/m2
(range: 3040); dose: 0.3
IU/kg
6
Glucose infusion rate
(mg/kg/min)
Insulin
glulisine
Insulin lispro
RHI
100
50
0
0
0
120 240
Time (minutes)
120
240
360
480
600
Time (minutes)
GIRmax-t10%
min
p=0.014
6
min
INSmax-t10%
p=0.000
5
GIRmax-t20%
p=0.043
5
min
INSmax-t20%
p=0.000
5
Insulin lispro
*p<0.05; **p<0.001 vs
Dose 0.2 U/kg
(N=80)
10
8
**
6
4
**
*
2
0
All
<25 25303035 35
BMI groups (kg/m2)
insulin lispro
10
**
8
6 **
**
4
2
0
All
<25 25303035 35
BMI groups (kg/m2)
HbA1c (%)
7.5
Insulin glulisine
RHI
7.4
7.3
7.2
7.1
7.0
6.9
Baseline
N=876 withT2DM;
BMI=34.6 kg/m2
and 34.51kg/m2 in
the insulin glulisine
and RHI groups
respectively;
NPH=basal insulin
*p<0.05
12 weeks
26 weeks
40
p=0.029*
9
p=0.049
9
30
20
22.
4
10
HbA1c (%)
Randomization
Endpoint
8.
0
7.
8
7.
8
7.5
8.8
0
6
Control
group
Glargine
+ glulisine
Control
group
Glargine
+ glulisine
60
52.2
40
20
36.
5
p=N
S
HbA1c (%)
Baseline
Endpoint
p<0.000
1
7.3
5
7.0
3
p<0.000
1
7.2
9
6.9
4
6
Breakfast Main meal
group
group
Breakfast
group
Main meal
group
ain meal group also included subjects whose main meal was breakfast
10
p=NS
0.
5
0.4
0.2
0.
2
0.0
p=NS
8
6
7.6
8
8.19
4
2
0
Contr
ol
group
Glargine
+
glulisine
Control Glargine
group + glulisine
0.6
Symptomatic hypo
(event/patient-year)
0.2
p=NS
0.2
0.1
0.0
0.0
Control
group
Glargine
+
glulisine
1.0
0.8
1.
0
0.6
0.
9
0.4
0.2
0.0
Breakfast
group
Main
meal
p=NS
3.6
9
0.05
2.7
2
Breakfast
group
Main
meal
Severe hypo
(event/patient-year)
p=NS
1.2
Confirmed hypo
(event/patient-year)
0.04
0.04
0.03
0.02
0.01
0.0
1
0.00
Breakfast Main
group
meal
Perbandingan harga
Summary (1)
Summary (2)
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