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Inititation and Dose Optimization Basal

Insulin
in DM Patient: Are All Basal Insulin
Same ?

Speaker: __________________

Content
Basal insulin: Asian perspective

Insulin glargine: initation & dose titration

Insulin glargine: dose optimization

Content
Basal insulin: Asian perspective

Insulin glargine: initiation & dose titration

Insulin glargine: dose optimization

Majority of T2DM patients in Asia fail to


achieve glycemic targets (HbA1c <7%)
The JADE program
Significant proportion of patients with diabetes do not achieve any
target
Taiwa Thailan
Total
(n=368
7)

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

So WY, et al. J Diabetes


2011;3:10918.

Initiation of basal insulin is often


delayed in Asia
FINE Asia study1
T2DM patients were poorly controlled, with a diabetes
duration of 9.3 years and an HbA1c level of 9.8% at basal
insulin initiation in the FINE Asia study

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

International guidelines recommend considering


initiation of basal insulin soon after the failure of
monotherapy;3 despite this, evidence suggests that
insulin initiation in Asia is often delayed
The average time to initiation of insulin is 9 years 1,2
CREDIT, Cardiovascular Risk Evaluation in people with Type 2 Diabetes on
Insulin Therapy;
FINE, First Basal Insulin Evaluation; T2DM, type 2 diabetes mellitus

1. Tsai ST, et al. J Diabetes 2011;3:20816;


2. Balkau B, et al. Diabetes Res Clin Pract 2015;
108:43240;
3. Inzucchi SE, et al. Diabetes Care 2015;38:140
9.

Contributions of basal and postprandial


hyperglycemia in insulin-nave T2DM patients

On OAD therapy, fasting (basal) hyperglycemia dominates


over a wide range of HbA1c*
Postprandial hyperglycemia

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

OAD, oral antidiabetic drug; T2DM, type 2 diabetes mellitus


*Pooled baseline data from six treat-to-target studies (n=1699 T2DM patients on
1cdiet
OADs). Mean HbA1
8.69%, FPG 10.8 mmol/L (194 mg/dL). Calculations assume hyperglycemia is >5.6
mmol/L (100 mg/dL)

Baseline HbA

ranges
Riddle M, et al. Diabetes Care 2011;
34:250814.

Early intervention with basal insulin


maintains glycemic control in the long term
Clinical
Clinical inertia
inertia
OAD
OAD
OAD
OAD
OAD
monotherapy
+ multiple daily
Diet
Intervention
monotherapy uptitration combination+ basal insulin insulin injections
!

HbA1c (%)

10

Intervention!

Basal
Basal insulin
insulin
Intervention!
Intervention!

Intervention!

Duration of diabetes (years)


OAD, oral antidiabetic drug;

Del Prato S, et al. Int J Clin Pract


2005;59:134555.

ADA/EASD position statement 2015


ADA/EASD guidelines recommend that if target
HbA1c (<7%) is not achieved within 3 months of
monotherapy with metformin along with healthy
eating, weight control, increased physical activity
and diabetes education treatment intensification
with a two-drug combination should be initiated.
Among the different options for dual therapy with
metformin, the guidelines state that basal insulin is
of the highest efficacy

ADA, American Diabetes Association;


EASD, European Association for the Study
of Diabetes

Inzucchi SE, et al. Diabetes Care


2015;38:1409.

Insulin glargine is an extensively


studied basal insulin used for diabetes
treatment
Indication: Insulin glargine (Lantus) is a long-acting
insulin analog indicated to improve glycemic control
in adults and pediatric patients with type 1 diabetes
mellitus and in adults with T2DM. Insulin glargine
can be administered at any time of the day but
should be administered once a day at the same time
every day1
Insulin glargine offers flexible dose adjustments to meet
individual patients needs2,3

T2DM, type 2 diabetes


mellitus

1. Sanofi. LANTUS (Insulin Glargine) Prescribing


Information. USA, 2015;
2. Strange P. J Diabetes Sci Technol 2007;1;5408;
3. Barnett A. Clin Ther 2007;29:98799.

Content
Basal insulin: Asian perspective

Insulin glargine: initiation & dose titration

Insulin glargine: dose optimization

How to
Start?

APAN MEMULAI TERAPI INSULIN?


sedikitnya 3 bulan
terapi GHS + 2 OHO:

A1c >7 % dan


Glukosa Puasa>100

Glukosa Darah

A1c > 9 %
GHS: Gaya Hidup
Sehat
Konsensus Perkeni 2015

ADA/EASD 2015: approach to starting


and adjusting insulin in T2DM
Basal insulin alone is the most convenient initial
regimen, beginning at 10 U or 0.10.2 U/kg,
depending on the degree of hyperglycemia. It is
usually prescribed in conjunction with metformin
and possibly one additional non-insulin agent.
Once insulin is initiated, dose titration is
important

ADA, American Diabetes Association;


EASD, European Association for the Study
of Diabetes;
T2DM, type 2 diabetes mellitus

Inzucchi SE, et al. Diabetes Care


2015;38:1409.

Dose titration of insulin


glargine
The dose of insulin glargine should be adjusted
according to an individuals metabolic needs and
blood glucose measurements to reach their
glycemic control goal
The dosage of insulin glargine should be
individualized under the supervision of a treating
healthcare professional

Sanofi. LANTUS (Insulin Glargine) Prescribing


Information. USA, 2015.

Are All Basal Insulin the same?

Lantus includes one amino acid

substitution and two amino acid additions


(compared to human insulin)
Asparagine #21, A chain, replaced by
glycine
2 ARGININE added to end of B chain

Stabilit
y
Pergeseran titik
isolelektrik
(membantu mendekati pH

Ideal Basal Insulin


A basal insulin that closely mimics normal
pancreatic basal insulin secretion
Continued effect over 24 hours
No distinct peak
Reduced nocturnal hypoglycemia
Once daily administration for patient compliance
Predictable absorption pattern with a consistent
onset and duration of action

16 hours
24 hours

Long Acting Insulin Analog


Insulin Glargine

Peakless
Clear solution
Basal Insulin
Could be given 1 2
times a day
Not for intravenous
use

Insulin Activity Profile

Plasma Glucose Throughout the


Clamp Study

Insulin Detemir vs Insulin Glargine


in a Basal-bolus Regimen: A1C
levels at 26 weeks.

Insulin Detemir vs Insulin Glargine


in a Basal-Bolus Regimen:
Glycemic Control Achieved

HbA1c is reduced to 7% with once daily administration


in the majority of Lantus studies
T1-basal
bolus

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)

Porcellati F, et al. Diabet Med 2004;21:12131220


APOLLO study. Bretzel RG. Diabetes 2006;55(Suppl 1): Abstract 326-OR
INSIGHT study. Gerstein H, et al. Diabet Med 2006;23(7):736742.
INITIATE study. Yki-Jarvinen H, Diabetes 2006;55(Suppl 1): Abstract 125Treat-to-target study. Riddle M, et al. Diabetes Care 2003;26:30803086
OR
CHO counting study. Bergenstal R, et al. Diabetes 2006;55(Suppl 1): 441-

Insulin detemir: HbA1c is < 7% in only one study

Home P, et al. Diabetes Care 2004;27:10811087


Russell-Jones, D et al. Clin Ther 2004;26:724736
De Leeuw I, et al. Diabetes Obes Metab 2005;7:7382
Pieber TR, et al. Diabet Med 2005;22:850857
Hermansen, K et al. Diabetologia 2004;47:622629
Vague P, et al. Diabetes Care 2003;26:590596
Standl E, et al. Diabetes Technol Ther 2004;6:579588
Hermansen K, et al. Diabetes Care 2006;29:12691274

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

Study 1337. EMEA European public assessment report. Scientific


discussion
http://www.emea.eu.int/humandocs/PDFs/EPAR/levemir/093604en6.pdf
Study 1166. EMEA European public assessment report. Scientific
discussion
http://www.emea.eu.int/humandocs/PDFs/EPAR/levemir/093604en6.pdf
Study 1373. Rosenstock J, et al. Diabetes 2006;55(Suppl 1): Abstract 555-P
Haak T, et al. Diabetes Obes Metab 2005;7:5664.

Efficacy Results
Parameter
A1C at endpoint
(baseline adjusted)
Insulin dose at
endpoint
(median doses)

Detemir

Glargine

7.16%

7.12%

0.63 U/kg (0.02-3.96)


Total (QD & BID)
0.43 U/kg (0.02-1.98)
QD (45% of pts)

0.40 IU/kg

0.85 U/kg (0.14-3.96)


BID (55% of pts)

Completion rate

80%

87%

In-clinic FPG (mg/dl)

129.6

129.6

Rosenstock J, et al. Diabetologia 2008;51(3):408416

Glycemic Control Achieved


60
52

52

Percent of patients

50
40

34

35

30

Detemir
Glargine

20
10
0
A1c <7%

Rosenstock J, et al. Diabetologia 2008;51(3):408416

A1c <7 % w/o hypo

Efficacy Results
To reach efficacy to a similar level to once-daily Insulin Glargine, detemir requires
higher dose (77%) and often two injections

Baseline HbA1c=8.6% in both groups


Rosenstock J, et al. Diabetologia 2008;51(3):408416

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

Baseline HbA1c=8.6% in both groups


Rosenstock J, et al. Diabetologia 2008;51(3):408416

28

Dailey et al: to reach a similar HbA1c efficacy as Insulin


Glargine, detemir required a significantly higher dose
Compared with Insulin Glargine, patients using detemir required a significantly
higher dose to achieve the same HbA1c

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

Pts withdrawals due to adverse event N (%)

23 (7.9)

11 (3.85)

Injection site disorders


# of pts (# of events)

13 (13)

4 (5)

* Episodes / pt-year; **Total episodes


Rosenstock J, et al. Diabetologia 2008;51(3):408416

Glargine is associated with significant


lower risk of hypoglycemia
Reduction in reported hypoglycaemia following initiation of
basal insulin

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

Insulin Detemir Dosing and Insulin


Cost in T2DM: Mean Daily Insulin
Cost

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

After 90 yrs of uncertainty regarding the


safety of insulin in type 2 diabetes we
now know its long-term (6-7 year) effect on
important health
outcomes
The ORIGIN Trial investigators. N Engl J Med 2012;367;319-28

Section 4

Comparison of insulin glargine and insulin detemir


against the ideal insulin profile
Insulin
glargine

Insulin
detemir

Peakless, 24-hour profile enabling once-daily dosing

Low variability

Good glycaemic control with low incidence of hypoglycaemia

Easy titration to ambitious targets


Minimal weight change
Improved HRQoL and treatment satisfaction
Proven long-term safety

evidence to support this claim


weak or inconclusive evidence to support this claim
no evidence to support this claim

35

Approach to Starting and Adjusting Insulin in Type 2 Diabetes


#
Inj
1

Adjust: 10%-15% or 2-4 U once-twice weekly to reach


FBG target
For hypoglycemia: Determine and address cause; dose
by 4 U or 10-20%

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

Adjust: dose by 1-2 U or 10-15%


once-twice weekly until SMBG target
reached
For hypoglycemia: Determine and
address cause; corresponding
dose by 2-4 U or 10-20%

once-twice weekly until SMBG target


reached
For hypoglycemia: Determine and
address cause; corresponding
dose by 2-4 U or 10-20%

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

Adjust: dose by 1-2 U or 10-15% once-twice weekly until SMBG target


reached
For hypoglycemia: Determine and address cause; corresponding dose by
2-4 U or 10-20%

Flexibility More
FBG, fasting blood glucose; GLP-1-RA, GLP-1
receptor agonist;

Less
ADA. Diabetes Care 2016; 39 (Suppl. 1): S60-S71

A stepwise approach for the treatment of


patients with type 2 diabetes
A1C
<7.0%
Preprandial capillary PG
80130 mg/dl
Peak postprandial capillary PG
<180 mg/dl
ADA-2015

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

HbA1c uncontrolled, FBG on target


PPBG>8.8 mmol/l (>160 mg/dl)
Time
Raccah D. Diabetes Ob Met 2008; 10: 76-82
Adapted from ADA. Diabetes Care 2015;38(Suppl.1)

Insulin titration according to the


guidelines

Once initiated, basal insulin is ideally titrated from a low starting


dose (usually
10 U/day) toADA/EASD
achieve therapeutic efficacy using various titration
AACE/ACE 2015
IDF 2012
2015
algorithms
2

Initial dose
per day

Titration

Target FPG,
mg/dL
Target
HbA1c, %
Down

FPG, fasting plasma


titrationglucose;
FBG, fasting
blood
dealing
glucose

with
hypoglycem

10 U/day or
0.1
0.2/kg/day

HbA1c <8%: 0.10.2 U/kg


HbA1c >8%: 0.20.3 U/kg

Starting doses of insulin


for safety reasons
should be low

increase
dose 24 U
once or
twice
weekly

Fixed regime: increase dose 2


U/day
Adjustable regime:
FBG> 180 mg/dL: increase dose
by 4 U
FBG 140180 mg/dL: increase
dose by 2 U
FBG 110139 mg/dL: increase
dose by 1 U

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.

BG <70 mg/dL: decrease dose by

Inzucchi SE, et al. Diabetes Care 2015;38:1409;


1020%
Handelsman Y, et al. Endo Pract 2015;21:1-87;
BG <40Diabetes
mg/dL:
decrease
byfor Type 2 Diabetes. 2012;
International
Federation.
Globaldose
Guideline
Available
at: http://www.idf.org/sites/default/files/IDF-Guideline-for-Type-2-Diabetes.pdf
2040%
(accessed October 2015).

Simple up/down treat-to-target titration


algorithms with insulin glargine for individual
dose adjustments

Different titration algorithms based on FPG values have proven to


be effective
in numerous
clinical
studies Down titration- dealing
Study
FPG
Dose
Frequency
(mmol/L)

titration

of dose
titration

with hypoglycemia

INSIGH
T1

Until 5.5

Add 1 unit

Daily

Doses were reduced at the


discretion of the investigator
in response to biochemical
or
clinical hypoglycaemia

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

HbA1c goals are attained with insulin glargine


using simple titration algorithms
Mean HbA1c
attained in various Treat-to-Target trials
Baseline
9

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.

Optimized titration can lead to


effective glycemic control
Once insulin is initiated, dose titration is
important1,2
Dose titration is patient-specific and should be
done in order to achieve target fasting blood
glucose3
Adequate titration of the insulin dose, either by
physicians or by patients, can help patients reach
treatment goals, including HbA1c <7% and FBG <5.5
mmol/L (<100 mg/dL)2
The choice between algorithms may depend on
clinical circumstances
and a patients willingness and ability to become
2
more involved in management of therapy
1.Inzucchi SE, et al. Diabetes Care
FBG, fasting blood
glucose;

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

Insulin glargine: initiation & dose titration


Insulin glargine: dose optimization

Mean HbA1c reduction with insulin


glargine in T2DM
Glycemic control in insulin-nave T2DM on OADs

Mean HbA1c (%)

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)

a, insulin glargine; Met, metformin; OADs, oral antidiabetic drugs;


DM, type 2 diabetes mellitus; SU, sulfonylurea

Baseli

24

Gla
+ SU
ne + Met
weeks
(n=1,268)

1.6%

7.2

Baseli 24
Overall
ne
weeks

(n=2,728)

DeVries H, et al. Eur Endocrinol 2014;


10: 2330.

Proportion of patients achieving target


HbA1c
at Week 24
Patients (%) achieving HbA1c
endpoint at 24 weeks

Responder rates for glargine/OAD pools and overall


50
45
40
35
30
25
20
15
10
5
0

44.6
39.8

35.4

34
24.1

26.4

24.3

15.9
HbA1c
<7%

HbA1c
<7.5%

Gla + Met
(n=634)

Gla, insulin glargine; Met, metformin;


OAD, oral antidiabetic drug; SU, sulfonylurea

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)

Owens DR, et al. Diabetes Res Clin Pract


2014;106:26474 (suppl).

Reduction of HbA1c at 12 and 24 weeks with


Gla + metformin + SU
By Week 12, about 88% of max. HbA1c effect achieved compared

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

Mean HbA1c (%)

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

Gla, insulin glargine; Met,


metformin; SU, sulfonylurea

Owens DR, et al. Diabetes Res Clin Pract


2014;106:26474 (suppl).

B
ne as
el
W i
12 k
W
24 k

Insulin dose profiles by weight


(U/kg) over time

Gla, insulin glargine; Met, metformin; SU,


sulfonylurea

Owens DR, et al. Diabetes Res Clin Pract


2014;106:26474.

Rates of hypoglycemia with insulin glargine


during titration and maintenance period
Insulin glargine therapy is well tolerated during
uptitration and maintenance
Episodes per patient-year

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

PG, plasma glucose

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)

Owens DR, et al. Diabetes Res Clin Pract 2014;106:26474 (su


2. DeVries H, et al. Endocrinol 2014;10:23

There is a need to better understand basal


insulin dose titration in the Asian population
Asia is characterized by a relatively young onset of T2DM and low
BMI1
Asian individuals show a higher percentage of body fat and
greater abdominal obesity compared with Western patients with
an equivalent BMI1
Asian patients with T2DM may require a lower insulin dose
compared with non-Asian populations
In the FINE Asia study, initiation of basal insulin resulted in reduction of
mean HbA1c levels from 9.8 to 7.7% over 6 months. Mean basal insulin
dose titration of 0.220.24 U/kg/day was required to achieve this 2%
reduction in HbA1c1
A Global Patient-level analysis (that included regions like Europe, America,
Australia and Asia) showed 1.7% HbA1c reduction on patients on Gla +
Met**
and 56.8% reached target HbA1c <7%2** with dose titration to 0.52 U/kg2
* 15 TTT studies pooled patient level analysis
BMI, body mass index; FINE, FINE, First Basal Insulin
Evaluation;
Gla, insulin glargine; Met, metformin; SU,
sulfonylurea
T2DM, type 2 diabetes mellitus
** At Week 24

1. Tsai ST, et al. J Diabetes 2011;3:20816;


2. Owens DR, et al. Diabetes Res Clin Pract
2014;106:26474 (suppl).

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

No increased hypoglycemia risk with insulin glargine during


titration period compared with maintenance period2,3

* At Week
24
Gla, insulin glargine; Met, metformin; OAD, oral antidiabetic drug

1. Inzucchi SE, et al. Diabetes Care 2015;38:1409;


2. DeVries H, et al. Eur Endocrinol 2014;10:2330;
3. Owens DR, et al. Diabetes Res Clin Pract
2014;106:26474 (suupl).

Summary (2)

Treating diabetes with insulin means trying to mimic normal


physiology
In comparison Glargine vs Detemir:
Glargine: has greater biological acitivity & higher potency
Glargine : has more patient to achieve HbA1C
Glargine : has less dosing insulin requirement; the real
once daily
Glargine: has lower daily cost therapy for patients
Glargine: has significant lower risk of hypoglycemia
Glargine: has long term safety data
Insulin glargine is the true once daily 24 hour basal insulin
analogue with peakless profile
Once-daily injection of insulin glargine is convenient and
improves patients compliance so they can achieve their HbA 1c
goals

Recommendation for Management


of Diabetes During Ramadan:
How to Achieve Glycemic Control and Safety

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

Al-arouj M, et al. Diabetes Care 2010;33(8):1895-902.

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

Al-arouj M, et al. Diabetes Care 2010;33(8):1895-902.

Major Risks with Fasting


Hypoglycemia
Hyperglycemia
Diabetic ketoacidosis
Dehydration and thrombosis

Al-arouj M, et al. Diabetes Care 2010;33(8):1895-902.

Risk Stratification Before


Ramadan Fasting

Assessment before RamadanRisk Stratification

Very high risk

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)

Al-arouj M, et al. Diabetes Care 2010;33 (8) 1895-902

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

Risk for hypo- and hyperglycemia also in


T2DM, but risk not as high
Need medical assesment on the patient
clinical profile prior to face Ramadan
Al-arouj M, et al. Diabetes Care 2010;33(8):1895-902.

Summary
Need dose adjustment in some
pharmacological agent during Ramadan
Insulin basal (Glargine ) provide
good safety

Al-arouj M, et al. Diabetes Care 2010;33(8):1895-902.

Thank you