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Insulin
in DM Patient: Are All Basal Insulin
Same ?
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Content
Basal insulin: Asian perspective
Content
Basal insulin: Asian perspective
HK
(n=83
2)
India
(n=78
8)
Korea
(n=29
5)
Philippine
s
(n=1186)
Singapor
e
(n=256)
35.3
61.8
13.8
40.7
31.3
No
targe
ts
32.6
14.3
38.3
28.1
1
targe
t
38.7
37.1
40.6
2
targe
ts
23.4
36.3
19.2
n
(n=55
)
d
(n=275
)
35.2
25.5
29.8
42.2
42.8
40.0
23.3
36.6
39.2
37.9
43.6
37.5
29.8
16.2
15.2
12.7
29.8
HbA
1C
<7%
HK, Hong Kong; JADE, Joint Asia Diabetes Evaluation; T2DM, type 2
diabetes mellitus
CREDIT study2
T2DM patients were also poorly controlled, with a
diabetes duration of 9 years and an HbA1c level of 9.2% at
insulin initiation in the CREDIT study
Basal hyperglycemia
100
80
60
76
78
79
79
80
24
22
21
21
20
<8.0
8.0<8.5
8.5<9.0
9.0<9.5
9.5
40
20
0
Baseline HbA
ranges
Riddle M, et al. Diabetes Care 2011;
34:250814.
HbA1c (%)
10
Intervention!
Basal
Basal insulin
insulin
Intervention!
Intervention!
Intervention!
Content
Basal insulin: Asian perspective
How to
Start?
Glukosa Darah
A1c > 9 %
GHS: Gaya Hidup
Sehat
Konsensus Perkeni 2015
Stabilit
y
Pergeseran titik
isolelektrik
(membantu mendekati pH
16 hours
24 hours
Peakless
Clear solution
Basal Insulin
Could be given 1 2
times a day
Not for intravenous
use
T2-basal
bolus
T2-Lantus + OADs
12months
24 weeks
24 weeks
(n=60)
(n=206) p=0.0007 vs
(n=367)
p<0.05 vs NPH conventional therapy NS vs NPH
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
Efficacy Results
Parameter
A1C at endpoint
(baseline adjusted)
Insulin dose at
endpoint
(median doses)
Detemir
Glargine
7.16%
7.12%
0.40 IU/kg
Completion rate
80%
87%
129.6
129.6
52
Percent of patients
50
40
34
35
30
Detemir
Glargine
20
10
0
A1c <7%
Efficacy Results
To reach efficacy to a similar level to once-daily Insulin Glargine, detemir requires
higher dose (77%) and often two injections
Efficacy Results
To reach efficacy of a similar level to Insulin Glargine, detemir is given
twice daily in 55% of patients
55%
Twice-daily
45%
Once-daily
28
DaileyG,etal.ADA2009,abstractaccepted
Efficacy Results
similar weight gain versus Insulin Glargine when used twice daily
*p<0.001;
Rosenstock J, et al. Diabetologia 2008;51(3):408416
p<0.012
Safety Results
Event
Detemir
QD-BID
Glargine
QD
Hypoglycemia*
5.8
6.2
Nocturnal Hypoglycemia*
1.3
1.3
Major**
Requiring assistance
At Night
23 (7.9)
11 (3.85)
13 (13)
4 (5)
9%
30%
Glargine
n=5,683
P<0.05
Detemir
N=694
P>0.05,
1. Currie CJ et al. Curr Med Res Opin 2007;23(Suppl 1): S33-S39
Study
Study Design
N=12,537; 573 sites; 40 countries; Median (IQR) Follow-up:
6.2 y (5.8-6.6)
Early addition of basal insulin glargine for > 6 yrs.
o is possible & feasible
o has a neutral effect on CVD, cancers, other outcomes
o reduces progression of diabetes
o modestly increases weight & hypoglycemia incidence
Insulin glargine is now the best-studied of all glucoselowering drugs
No new side effects of basal insulin over 6-7 years
Section 4
Insulin
detemir
Low variability
35
If not
controlled after
FBG target is reached
Add 1 rapid insulin
Change to premix
(or if dose >0.5 U/kg/day),
injection before
insulin twice daily
treat PPG excursions with
largest
meal
Start: 4 U/day or 0.1 U/kg, or 10%
mealtime insulin
Start: Divide current basal dose into
basal dose. If A1C <8%, consider
(Consider initial
AM, PM or AM, PM
bolus by same amount
GLP-1-RA trial)
Adjust: dose by 1-2 U or 10-15%
3+
Compl exity
Low
Basal Insulin
(usually with metformin +/1 other noninsulin
agent(s)
Start: 10 U/day or
0.1-0.2 U/kg/day
If not
If not
controlled,
controlled,
Add 2 rapid insulin injections
consider
basalconsider basal(basal-bolus)
Start: 4 U/day orbefore
0.1 U/kg,meals
or 10% basal
dose/meal. If A1C <8%, consider
bolus
bolus
bolus by same amount
Mod
High
Flexibility More
FBG, fasting blood glucose; GLP-1-RA, GLP-1
receptor agonist;
Less
ADA. Diabetes Care 2016; 39 (Suppl. 1): S60-S71
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
Initial dose
per day
Titration
Target FPG,
mg/dL
Target
HbA1c, %
Down
with
hypoglycem
10 U/day or
0.1
0.2/kg/day
increase
dose 24 U
once or
twice
weekly
Self-titration
regimen: insulin dose
increases of 2 U every 3
days
Physician led:
biweekly or more
frequent contact with a
health-care professional
<110
<115
<7
<7
<7
Decrease
dose by 41.
2.
U
3.
titration
of dose
titration
with hypoglycemia
INSIGH
T1
Until 5.5
Add 1 unit
Daily
LANME
T2
>10
>5.5
TTT3
Every 3
days
Add 8
Weekly
Severe hypoglycaemia:
units
decrease in insulin dose 24
U/day per adjustment
Add 6
units
Add 4
FPG, fasting plasma glucose; INSIGHT, Implementing
New
Strategies with Insulin Glargine for Hyperglycaemia
Treatment;
units
LANMET, Insulin glargine or NPH combined with metformin in type 1.Gerstein HC, et al. Diabetes Med 2006;23:73642;
2. Yki-Jrvinen H, et al. Diabetologia 2006;49:44251;
2 diabetes; TTT, Treat-to-Target Trial
Add 2
3. Riddle MC, et al. Diabetes Care 2003;26:30806.
units
10
7.810
6.77.8
5.66.7
Add 4
units
Add 2
units
8.6
8.6
HbA1c%
8
7
Study end
8.7
1.6
7.0
8.8
1.6
7.0
8.7
1.7
7.0
6.8
2.0
1.7
7.0
6
5
1
Study name TTT
Patient
population n=367
Study duration
24 weeks
INSIGHT
n=206
24 weeks
Typically ~50%
2
3
4
5
APOLLO
INITIATE
Observational
n=174
n=581. Riddlen=11,511
MC, et al. Diabetes Care 2003;26:3080
6;
44
weeks
24
weeks
9
months 15
of patients attain HbA <7%15
2. Gerstein
et al. Diabetes Med 2006;23:736
Typically ~50% of patients attain
HbAHC,<7%
1c
1c
42;
APOLLO, Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people
3. Bretzel RG, et al. Lancet 2008;371:107384;
with type 2 diabetes on oral hypoglycaemic agents; INITIATE, Initiate Insulin by Aggressive
4. Yki-Jrvinen H, et al. Diabetes Care
Titration and Education; TTT, Treat-to-Target Trial; INSIGHT, Implementing New Strategies with
Insulin Glargine for Hyperglycaemia Treatment; Observational, Insulin glargine benefits
2007;30:13649;
patients with type 2 diabetes inadequately controlled on oral antidiabetic treatment.
5. Schreiber SA & Haak T. Diabetes Obes Metab
2007;9:318.
2015;38:1409;
2. Barnett A. Clin Ther 2007;29:98799;
3. Agarwal SK, et al. J Indian Med Assoc
2013;111:6268.
Content
Basal insulin: Asian perspective
10
9
9.0
8.7
8.8
8.7
1.4%
8
7
6
1.7%
1.6%
7.6
7.1
Baseli 24
Gla + weeks
Met
ne
(n=593)
Baseli
Gla
ne
24
+weeks
SU
(n=867)
Baseli
24
Gla
+ SU
ne + Met
weeks
(n=1,268)
1.6%
7.2
Baseli 24
Overall
ne
weeks
(n=2,728)
44.6
39.8
35.4
34
24.1
26.4
24.3
15.9
HbA1c
<7%
HbA1c
<7.5%
Gla + Met
(n=634)
HbA1c
<7%
HbA1c
<7.5%
Gla + SU
(n=906)
HbA1c
<7%
HbA1c
<7.5%
Gla + Met + SU
(n=1,297)
HbA1c
<7%
HbA1c
<7.5%
Overall
(n=2,837)
with 24 study
weeks analysis of Gla + Met + SU treatment
Single
(12
1.5
wks)
(24
1.6
wks)
1.3
1.4
1.4
1.5
10.0
9.0
1.4
1.6
1.5
1.6
0.7
0.8
1.4
1.7
1.8
1.7
1.8
1.8
0.9
1.6
Baseline
Week 12
Week 24
9.7
9.1
8.7
8.8
8.5
8.5
8.0
7.37.2
7.0
7.27.1
8.9
7.17.0
7.4
7.1
7.5
7.2
7.4
7.1
9.0
8.7
8.7
7.5
7.1
6.9
7.27.1
7.2
6.86.7
6.0
B
ne as
el
W i
12 k
W
24 k
PG-cutoff
(mmol/L):
<3.9<3.1<3.9<3.1<2.0
<3.9<3.1<3.9<3.1<2.0
<3.9<3.1<3.9<3.1<2.0
7.0
6.0
5.0
4.1
4.0 3.6
3.9
3.0
2.0
1.0
0.0
1.1
1.4
0.5
0.2
0.3
1.3
0.7
0.00.3
0.6
0.0
0.0
012 weeks1
(titration)
1224 weeks1
(maintenance)
1.
024 weeks2
(n=2837)
Summary (1)
Insulin glargine is ideally titrated from a low starting dose to
an appropriate dose/kg/day to achieve glycemic goals with
various titration algorithms
Starting dose at 10 U/day or 0.10.2/kg/day1
In patients on Gla + Met* a 1.7% HbA1c reduction has been
demonstrated and 56.8% reached target HbA1c <7%2* with dose
titration to 0.52 U/kg2, 3 from 15 TTT studies pooled patient level
analysis
With Treat-to-Target titration algorithms: by Week 12, >80% of the
maximum treatment effect (in terms of reductions in HbA1c) had
been achieved compared with glycemic control at Week 24 for
each concomitant OAD treatment regimen with insulin glargine
* At Week
24
Gla, insulin glargine; Met, metformin; OAD, oral antidiabetic drug
Summary (2)
Pathophysiology of
Fasting:Three Stages
1) Post-absorptive phase: 6-24 hours
after beginning the fast
2) Gluconeogenic phase: from 2-10
days
of fasting
3) The protein conservation phase,>10
days of fasting
Pathophysiology of
Fasting
After an overnight fast, average rate of
glucose utilization in healthy adults is
approx. 7 g/hr
70-80 g glycogen in liver can provide
glucose to the brain and peripheral
tissues for about 12 hrs
High risk
Moderate risk
Severe hypoglycemia
within the 3 months prior
to Ramadan
A history of recurrent
hypoglycemia
Hypoglycemia
unawareness
Sustained poor glycemic
control
Ketoacidosis within the 3
months prior to Ramadan
Type 1 diabetes
Acute illness
Hyperosmolar
hyperglycemic coma within
the previous 3 months
Performing intense
physical labor
Pregnancy
Chronic dialysis
Moderate hyperglycemia
(average blood glucose
150300 mg/dl or A1C 7.5
9.0%)
Renal insufficiency
Advanced macrovascular
complications
Living alone and treated
with insulin or
sulfonylureas
Patients with comorbid
conditions that present
additional risk factors
Old age with ill health
Treatment with drugs that
may affect mentation
Well-controlled diabetes
treated with short-acting
insulin secretagogues
(repaglinide or nateglinide)
Low risk
Well-controlled diabetes
treated with lifestyle
therapy, metformin,
acarbose,
thiazolidinediones, and/or
incretin-based therapies in
otherwise healthy patients
PERKENI 2015
:
Rekomendasi
Terapi DM
tipe 2
Ubah premixed
ataupun
Intermediate
insulin ke
Insulin kerja
panjang tanpa
penyesuaian
dosis.
Untuk rapid
insulin tidak
perlu ada
penyesuaian
Clinical Evidence
Summary
Fasting during Ramadan has risk for
patients with diabetes
Very high risk of complications for T1DM
Poorly controlled = high risk of
hypoglycemia
Excessive reduction in insulin
= risk for hyperglycemia and ketoacidosis
Summary
Need dose adjustment in some
pharmacological agent during Ramadan
Insulin basal (Glargine ) provide
good safety
Thank you