Initiation and Titration Basal Insulin

in Type 2 DM:
Fccus on Insulin Glargine
 Content

Basal insulin: Asian perspective

Insulin glargine: dose titration

Insulin glargine: dose optimization

 Content

Basal insulin: Asian perspective

Insulin glargine: 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

Total HK India Korea Philippines Singapore Taiwan Thailand

(n=3687) (n=832) (n=788) (n=295) (n=1186) (n=256) (n=55) (n=275)

HbA1C
35.3 61.8 13.8 40.7 31.3 35.2 25.5 29.8
<7%

No
32.6 14.3 38.3 28.1 42.2 42.8 40.0 23.3
targets
1
38.7 37.1 40.6 36.6 39.2 37.9 43.6 37.5
target
2
23.4 36.3 19.2 29.8 16.2 15.2 12.7 29.8
targets
3
5.4 12.3 1.9 5.4 2.5 3.1 3.6 9.5
targets
HK, Hong Kong; JADE, Joint Asia Diabetes Evaluation; T2DM, type 2 diabetes mellitus So WY, et al. J Diabetes 2011;3:109–18.
 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 years1,2

1. Tsai ST, et al. J Diabetes 2011;3:208–16;
CREDIT, Cardiovascular Risk Evaluation in people with Type 2 Diabetes on Insulin Therapy; 2. Balkau B, et al. Diabetes Res Clin Pract 2015; 108:432–40;
FINE, First Basal Insulin Evaluation; T2DM, type 2 diabetes mellitus 3. Inzucchi SE, et al. Diabetes Care 2015;38:140–9.
 Contributions of basal and postprandial
hyperglycemia in insulin-naïve 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%

40

20
24% 22% 21% 21% 20%
0
<8.0 8.0–<8.5 8.5–<9.0 9.0–<9.5 ≥9.5
Baseline HbA1c ranges
OAD, oral antidiabetic drug; T2DM, type 2 diabetes mellitus
*Pooled baseline data from six treat-to-target studies (n=1699 T2DM patients on diet ± OADs). Mean HbA1
8.69%, FPG 10.8 mmol/L (194 mg/dL). Calculations assume hyperglycemia is >5.6 mmol/L (100 mg/dL)
Riddle M, et al. Diabetes Care 2011; 34:2508–14.
 Early intervention with basal insulin maintains glycemic
control in the long term
Clinical inertia

OAD OAD
OAD monotherapy OAD OAD
Diet
Intervention! + multiple daily
monotherapy uptitration combination + basal insulin insulin injections
Intervention!
10 Basal insulin

9 Intervention!
HbA1c (%)

Intervention!
8
Intervention!

Duration of diabetes (years)

OAD, oral antidiabetic drug; Del Prato S, et al. Int J Clin Pract 2005;59:1345–55.
 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;38:140–9.
 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;540–8;
3. Barnett A. Clin Ther 2007;29:987–99.
 Content

Basal insulin: Asian perspective

Insulin glargine: dose titration

Insulin glargine: dose optimization

How to
Start?
 KAPAN 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 0.1–0.2 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;38:140–9.
 Dose titration of insulin glargine
• The dose of insulin glargine should be adjusted according to
an individual’s 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.

 Basal Insulin Analogue
● 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

Stability

Pergeseran titik isolelektrik

(membantu mendekati pH tubuh)
 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
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 T2-basal
bolus bolus
8
T2-Lantus + OADs

6.96 6.96 6.96

7 6.80
6.60 6.60
HbA1c(%)

5
Porcellati INSIGHT Treat-to- APOLLO INITIATE CHO counting
target
12months 24 weeks 24 weeks 44 weeks 24 weeks 24 weeks
(n=60) (n=206) p=0.0007 vs (n=367) (n=174) (n=58) (n=273)
p<0.05 vs NPH conventional therapy NS vs NPH NS vs 3 lispro

Porcellati F, et al. Diabet Med 2004;21:1213–1220 APOLLO study. Bretzel RG. Diabetes 2006;55(Suppl 1): Abstract 326-OR
INSIGHT study. Gerstein H, et al. Diabet Med 2006;23(7):736–742. INITIATE study. Yki-Jarvinen H, Diabetes 2006;55(Suppl 1): Abstract 125-
Treat-to-target study. Riddle M, et al. Diabetes Care 2003;26:3080–3086 OR
CHO counting study. Bergenstal R, et al. Diabetes 2006;55(Suppl 1): 441-
 Insulin detemir: HbA1c is < 7% in only one study

10 T1-basal bolus T2-Detemir+OADs T2-

Detemir
9.26 + Bolus

9
8.30 8.41
8.20
HbA1c (%)

7.75 7.88 7.88

8
7.53 7.65 7.60 7.60
7.46
7.20
7 6.80

Home P, et al. Diabetes Care 2004;27:1081–1087

Russell-Jones, D et al. Clin Ther 2004;26:724–736 Study 1337. EMEA – European public assessment report. Scientific
De Leeuw I, et al. Diabetes Obes Metab 2005;7:73–82 discussion
Pieber TR, et al. Diabet Med 2005;22:850–857 http://www.emea.eu.int/humandocs/PDFs/EPAR/levemir/093604en6.pdf
Hermansen, K et al. Diabetologia 2004;47:622–629 Study 1166. EMEA – European public assessment report. Scientific
Vague P, et al. Diabetes Care 2003;26:590–596 discussion
Standl E, et al. Diabetes Technol Ther 2004;6:579–588 http://www.emea.eu.int/humandocs/PDFs/EPAR/levemir/093604en6.pdf
Hermansen K, et al. Diabetes Care 2006;29:1269–1274 Study 1373. Rosenstock J, et al. Diabetes 2006;55(Suppl 1): Abstract 555-P
Haak T, et al. Diabetes Obes Metab 2005;7:56–64.
Section 4

Comparison of insulin glargine and insulin detemir

against the ideal insulin profile

Insulin Insulin
glargine 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
23
Approach to Starting and Adjusting Insulin in Type 2 Diabetes
# Basal Insulin Compl exity
Inj (usually with metformin +/1 other non-insulin agent(s) Low
1
• Start: 10 U/day or 0.1-0.2 U/kg/day
• 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
2 Add 1 rapid insulin injection Change to premix insulin
(or if dose >0.5 U/kg/day), treat PPG
before largest meal twice daily Mod
excursions with mealtime insulin
(Consider initial
• Start: 4 U/day or 0.1 U/kg, or 10% basal dose. If GLP-1-RA trial) • Start: Divide current basal dose into ⅔ AM, ⅓ PM
A1C <8%, consider  bolus by same amount or ½ AM, ½ PM
• Adjust:  dose by 1-2 U or 10-15% once-twice • Adjust:  dose by 1-2 U or 10-15% once-twice
weekly until SMBG target reached weekly until SMBG target reached
• For hypoglycemia: Determine and address cause; • For hypoglycemia: Determine and address cause;
 corresponding dose by 2-4 U or 10-20%  corresponding dose by 2-4 U or 10-20%

If not If not
3+ controlled, consider Add ≥2 rapid insulin injections before meals controlled, consider High
basal-bolus (“basal-bolus”) basal-bolus

• Start: 4 U/day or 0.1 U/kg, or 10% basal dose/meal. If A1C <8%, consider  bolus by same amount
• 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 Less

FBG, fasting blood glucose; GLP-1-RA, GLP-1 receptor agonist; ADA. Diabetes Care 2016; 39 (Suppl. 1): S60-S71
hypo, hypoglycemia; mod., moderate; PPG, postprandial glucose
 A stepwise approach for the treatment of
patients with type 2 diabetes

A1C <7.0% Basal Bolus

Preprandial capillary PG 80–130 mg/dl
Peak postprandial capillary PG <180 mg/dl Basal Plus
ADA-2015 Basal Plus Basal +
Two prandial three prandial
for largest
One prandial glucose
Basal Insulin for largest excursion
glucose
excursion
Once daily
OHA (optimized)
mono or
combination
therapy
Diet and
exercise
HbA1c HbA1c uncontrolled, FBG on target
uncontrolled 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) to achieve therapeutic efficacy using various titration algorithms
ADA/EASD
AACE/ACE 20152 IDF 20123
20151

10 U/day or HbA1c <8%: 0.1–0.2 U/kg Starting doses of insulin for

Initial dose per
0.1– HbA1c >8%: 0.2–0.3 U/kg safety reasons should be low
day
0.2/kg/day
increase dose Fixed regime: increase dose 2 U/day Self-titration regimen: insulin
2–4 U once or Adjustable regime: dose increases of 2 U every 3
twice weekly FBG> 180 mg/dL: increase dose by 4 U days
Titration
FBG 140–180 mg/dL: increase dose by 2 U Physician led: biweekly or
FBG 110–139 mg/dL: increase dose by 1 U more frequent contact with a
health-care professional
Target FPG,
mg/dL
- <110 <115

Target HbA1c, % <7 <7 <7

Down titration- Decrease BG <70 mg/dL: decrease dose by 10–20%

dealing with dose by 4 U BG <40 mg/dL: decrease dose by 20–40%
hypoglycemia

FPG, fasting plasma glucose; 1. Inzucchi SE, et al. Diabetes Care 2015;38:140–9;
FBG, fasting blood glucose 2. Handelsman Y, et al. Endo Pract 2015;21:1-87;
3. International Diabetes Federation. Global Guideline for Type 2 Diabetes. 2012;
Available at: http://www.idf.org/sites/default/files/IDF-Guideline-for-Type-2-Diabetes.pdf (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
Studynumerous clinical studies
FPG (mmol/L) Dose titration Frequency of Down titration- dealing with
dose titration hypoglycemia

INSIGHT1 Until ≤5.5 Add 1 unit Daily Doses were reduced at the
discretion of the investigator in
response to biochemical or
clinical hypoglycaemia
LANMET2 • >10 • Add 4 units Every 3 days
• >5.5 • Add 2 units

TTT3 • ≥10 • Add 8 units Weekly Severe hypoglycaemia: decrease in

• 7.8–10 • Add 6 units insulin dose 2–4 U/day per
• 6.7–7.8 • Add 4 units adjustment
• 5.6–6.7 • Add 2 units

FPG, fasting plasma glucose; INSIGHT, Implementing New Strategies with Insulin
Glargine for Hyperglycaemia Treatment; LANMET, Insulin glargine or NPH 1.Gerstein HC, et al. Diabetes Med 2006;23:736–42;
2. Yki-Järvinen H, et al. Diabetologia 2006;49:442–51;
combined with metformin in type 2 diabetes; TTT, Treat-to-Target Trial 3. Riddle MC, et al. Diabetes Care 2003;26:3080–6.
 HbA1c goals are attained with insulin glargine using
simple titration algorithms
Mean HbA1c attained in various Treat-to-Target trials
Baseline Study end
9 8.7 8.8 8.7
8.6 8.6

8  –1.6  –1.6  –1.7  –2.0  –1.7

7.0 7.0 7.0 7.0

HbA1c%

7 6.8

5
1 2 3 4 5
Study name
Patient population
INSIGHT Observational
Study duration n=206… n=11,511…
Typically ~50% of patients attain HbA1c<7%1–5
APOLLO, Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on 1. Riddle MC, et al. Diabetes Care 2003;26:3080–6;
oral hypoglycaemic agents; INITIATE, Initiate Insulin by Aggressive Titration and Education; TTT, Treat-to-Target Trial; 2. Gerstein HC, et al. Diabetes Med 2006;23:736–42;
INSIGHT, Implementing New Strategies with Insulin Glargine for Hyperglycaemia Treatment; Observational, Insulin 3. Bretzel RG, et al. Lancet 2008;371:1073–84;
glargine benefits patients with type 2 diabetes inadequately controlled on oral antidiabetic treatment. 4. Yki-Järvinen H, et al. Diabetes Care 2007;30:1364–9;
5. Schreiber SA & Haak T. Diabetes Obes Metab 2007;9:31–8.
 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 patient’s willingness and ability to become more involved in
management of therapy2

1.Inzucchi SE, et al. Diabetes Care 2015;38:140–9;

FBG, fasting blood glucose; 2. Barnett A. Clin Ther 2007;29:987–99;
3. Agarwal SK, et al. J Indian Med Assoc 2013;111:626–8.
 Efficacy Results
Parameter Detemir Glargine
A1C at endpoint
7.16% 7.12%
(baseline adjusted)
Insulin dose at 0.63 U/kg (0.02-3.96)
endpoint Total (QD & BID)
(median doses) 0.43 U/kg (0.02-1.98)
0.40 IU/kg
QD (45% of pts)
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):408–416

 Glycemic Control Achieved

60
52 52

50
Percent of patients

40 34 35

30 Detemir
Glargine
20

10

0
A1c <7% A1c <7 % w/o hypo
Rosenstock J, et al. Diabetologia 2008;51(3):408–416
 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):408–416
 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):408–416 33

 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

Dailey G, et al. ADA 2009, abstract accepted

 Efficacy Results
similar weight gain versus Insulin Glargine when used twice daily

*p<0.001; †p<0.012

Rosenstock J, et al. Diabetologia 2008;51(3):408–416

 Safety Results
Event Detemir Glargine
QD-BID QD
Hypoglycemia* 5.8 6.2
Nocturnal Hypoglycemia* 1.3 1.3
Major**
Requiring assistance 9 8

At Night 5 4
Pts withdrawals due to adverse event N (%) 23 (7.9) 11 (3.85)
Injection site disorders
13 (13) 4 (5)
# of pts (# of events)

* Episodes / pt-year; **Total episodes

Rosenstock J, et al. Diabetologia 2008;51(3):408–416
 Glargine is associated with significant lower risk of
hypoglycemia

Reduction in reported hypoglycaemia following initiation of basal insulin

9%

30%

Glargine® Detemir®
n=5,683 N=694
P<0.05 P>0.05, NS
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 glucose-lowering 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
 Content

Basal insulin: Asian perspective

Insulin glargine: dose titration

Insulin glargine: dose optimization

 Mean HbA1c reduction with insulin glargine in T2DM

Glycemic control in insulin-naïve T2DM on OADs

10

9.0
9 8.7 8.7 8.8
Mean HbA1c (%)

–1.4%
8 –1.6%
–1.7% –1.6%
7.6
7.1 7.2
7.0
7

6 Baseline 24 weeks Baseline 24 weeks Baseline 24 weeks Baseline 24 weeks

Gla + Met Gla + SU Gla + Met + SU Overall
(n=593) (n=867) (n=1,268) (n=2,728)

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

T2DM, type 2 diabetes mellitus; SU, sulfonylurea DeVries H, et al. Eur Endocrinol 2014; 10: 23–30.
 Proportion of patients achieving target HbA1c
at Week 24
Responder rates for glargine/OAD pools and overall

50
44.6
Patients (%) achieving HbA1c

45
39.8
endpoint at 24 weeks

40 35.4 34
35
30 26.4
24.1 24.3
25
20 15.9
15
10
HbA1c HbA1c HbA1c HbA1c HbA1c HbA1c HbA1c HbA1c
5 <7% <7.5% <7% <7.5% <7% <7.5% <7% <7.5%
0
Gla + Met Gla + SU Gla + Met + SU Overall
(n=634) (n=906) (n=1,297) (n=2,837)

Gla, insulin glargine; Met, metformin;

OAD, oral antidiabetic drug; SU, sulfonylurea
Owens DR, et al. Diabetes Res Clin Pract 2014;106:264–74 (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 weeks
Single study analysis of Gla + Met + SU treatment
 (12 wks) –1.5 –1.3 –1.4 –1.4 –1.6 –1.5 –1.6 –0.7 –0.8 –1.4
 (24 wks) –1.6 –1.4 –1.5 –1.7 –1.8 –1.7 –1.8 –1.8 –0.9 –1.6
Baseline Week 12 Week 24
10.0 9.7

9.1 9.0
Mean HbA1c (%)

8.9
9.0 8.7 8.8 8.7 8.7
8.5 8.5

8.0
7.4 7.5 7.4 7.5
7.3 7.2 7.2 7.1 7.2 7.2 7.2 7.1
7.1 7.0 7.1 7.1 7.1
6.9
7.0 6.8 6.7

6.0
L2T3 INSIGHT TTT TRIPLE 4021 LAPTOP APOLLO INITIATE TULIP Pooled
Therapy n=1,297
Gla, insulin glargine; Met, metformin;
SU, sulfonylurea Owens DR, et al. Diabetes Res Clin Pract 2014;106:264–74 (suppl).
 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;106:264–74.

 Rates of hypoglycemia with insulin glargine during
titration and maintenance period
• Insulin glargine therapy is well tolerated during uptitration
and maintenance
PG-cutoff
<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
(mmol/L):

7.0
Episodes per patient-year

6.0
5.0
4.1 3.9
4.0 3.6
3.0
2.0 1.4 1.3
1.1
1.0 0.5 0.7 0.6
0.2 0.00 0.3 0.005 0.3 0.005
0.0

0–12 weeks1 12–24 weeks1 (maintenance) 0–24 weeks2

PG, plasma glucose (titration) (n=2837)
1. Owens DR, et al. Diabetes Res Clin Pract 2014;106:264–74 (suppl);
2. DeVries H, et al. Endocrinol 2014;10:23–30.
 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 0.22–0.24 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 1. Tsai ST, et al. J Diabetes 2011;3:208–16;
T2DM, type 2 diabetes mellitus 2. Owens DR, et al. Diabetes Res Clin Pract 2014;106:264–74 (suppl).
** At Week 24
 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 0.1–0.2/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 1. Inzucchi SE, et al. Diabetes Care 2015;38:140–9;

Gla, insulin glargine; Met, metformin; OAD, oral antidiabetic drug 2. DeVries H, et al. Eur Endocrinol 2014;10:23–30;
3. Owens DR, et al. Diabetes Res Clin Pract 2014;106:264–74 (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 HbA1c goals
Thank you