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ESW/MAR-17/RTD LVM-2017/001

RTD LEVEMIR®

Early Insulin Initiation in


type 2 DM Management
Speaker Name
ESW/MAR-17/RTD LVM-2017/001

Outlines

• Prevalence
• Rationale for early initiation
• T2DM management and guideline
• Insulin Levemir® & A1Chieve study
Sources :
1. IDF Diabetes Atlas, 8th ed
Number of people with diabetes worldwide and per region in 2017 and 2045
(20-79 years)

Diabetes:
A Global Emergency

Sources :
1. IDF Diabetes Atlas, 8th ed
Prevalence of Obesity and Diabetes in Indonesia: Health Basic Research,
2013

IFG IGT UD-DM D-DM Total DM


Prevalence (%) of IFG, IGT and diabetes
2007 - 10.2 4.2 1.5 5.7 (>15 years), Indonesia, 2007 and 2013
2013 36.6 29.9 4.5 2.4 6.9

Health Basic Research, 2007 and 2013


T2DM: Progressive loss of insulin
secretion with increasing insulin resistance1
Impaired Undiagnosed Known
glucose tolerance diabetes diabetes

Insulin resistance

Insulin secretion
PPG
FPG

Microvascular complications
Macrovascular complications

1. Adapted from: Ramlo-Halsted BA, Edelman SV. Clincial Diabetes 2000;18(2): http://journal.diabetes.org/clinicaldiabetes/v18n22000/pg80.htm
Hyperglycemia affects both micro-vascular and macro-vascular complications

Macro-vascular

Micro-vascular

1. World Health Organization. http://www.who.int/diabetes/action_online/basics/en/index3.html


Diabetes Care Indonesia 2008
Diabetes related complications

80%

70% 68%

60%

50%

40%

30%

20% 15%
10% 8%
10% 6% 4% 4%
0%

Soewondo, P, et al. The DiabCare Asia 2008 Study – Outcomes on control and complications of type 2 Diabetets
patients in Indonesia. Med J Indones 2010; 19:235-44)
Risk of complications increases as HbA 1c increases

1000 patient-years

Microvascular disease
Incidence per

Myocardial infarction

Updated mean HbA1c (%)

Stratton et al. BMJ 2000;321:405–12


ESW/MAR-17/RTD LVM-2017/001

Outlines

• Prevalence
• Rationale for early initiation
• T2DM management and guideline
• Insulin Levemir® & A1Chieve study
Poor glycemic control (HbA1c) is a global problem
Patients
achieving
targets (%)
60 <7% <7%
50
53
40 51 <7%
<6.5%
30
36
20 31
10

0
USA Canada EUROPE Emerging countries*
(NHANES)1 (DICE)2 (CODE-2)3 (IDPMS)4
*Asia, Eastern Europe, Latin America and the Middle East and Africa

• In the real world, only 50% of patients do not achieve their glycemic goals1
1. Casagrande S, et al. Diabetes Care 2013;36:2271-9; 2. Harris SB, et al. Diabetes Res Clin Pract 2005;70:90-7;
3. Liebl A, et al. Diabetologia 2002;45:S23-8; 4. Chan JC, et al. Diabetes Care 2009;32:227-33.
Patients remain on multiple OAD therapy too long
8.9%

Clinical inertia exists despite:


41% had HbA1c ≥9.0%
• The benefits of timely glycemic
Patients (%)

control
• Guidelines encouraging earlier use
of insulin

22% had HbA1c ≥10.0% At insulin initiation in SOLVE:


• Average HbA1c was 8.9%

HbA1c (%) at insulin initiation


Reduction in HbA1c with OADs
−1.3%*

10.0 +0.2%
0.5%*
−1.0%*

9.0 Pre-treatment
Mean HbA1c (%)

Post-treatment

8.0

7.0

6.0
2 OADs 3 OADs 4 OADs Insulin

*p<0.001
OADs, oral antidiabetic drugs
Calvert et al. Br J Gen Pract 2007;57:455–60
Insulin remains the most efficacious glucose lowering agent

Decrease in HbA1c: Potency of monotherapy


HbA1c %

CHOOSING INSULIN EARLIER


FOR BETTER EFFICACY

Nathan et al., Diabetes Care 2009;32:193-203.


Early insulin treatment prolongs beta-cell function and promotes metabolic
control

Alvarsson et al. Diabetes Care 2003;26:2231–7


Early insulin therapy improves beta-cell function and glycemic control

CSII, continuous subcutaneous insulin infusion; MDI, multiple daily injection; OHA, oral hypoglycaemic agent
Weng et al. Lancet 2008;371:1753–60
ESW/MAR-17/RTD LVM-2017/001

Outlines

• Prevalence
• Rationale for early initiation
• T2DM management and guideline
• Insulin Levemir® & A1Chieve study
How to individualize
Insulin Treatment
In Type 2 DM
American Diabetes Association. Diabetes Care Volume 41, Supplement 1, January 2018
Anti-hyperglycemic therapy in adults with type 2 diabetes

A1C is less than 9%, consider monotherapy.

A1C is greater than or equal 9%, consider dual therapy.

A1C is greater than or equal 10%, blood glucose is greater than or equal 300 mg/dL, or
patient markedly symptomatic, consider combination injectable therapy.

Monotherapy Lifestyle Management + Metformin

Initiate metformin therapy if no contraindications* (See table 8.1)

A1C at target Yes: - Monitor A1C every 3-6 months


After 3 months No: - Assess medication-taking behaviour
Of monotherapy - Consider dual therapy

Dual Therapy
American Diabetes Association. Diabetes Care Volume 41, Supplement 1, January 2018
Anti-hyperglycemic therapy in adults with type 2 diabetes
A1C is less than 9%, consider monotherapy.

A1C is greater than or equal 9%, consider dual therapy.

Monotherapy

Dual Therapy Lifestyle Management + Metformin + Additional Agent

ASCVD? Yes: - Add agent proven to reduce major adverse


cardiovascular events and/or cardiovascular mortality
(see recommendations with* on Table 8.1 p.S75)
No: - Add second agent after consideration of drug-spesific
effects & patients factors (see Table 8.1)

A1C at target Yes: - Monitor A1C every 3-6 months


After 3 months No: - Assess medication-taking behaviour
Of dual therapy - Consider triple therapy

Triple Therapy
American Diabetes Association. Diabetes Care Volume 41, Supplement 1, January 2018
Anti-hyperglycemic therapy in adults with type 2 diabetes
A1C is less than 9%, consider monotherapy.

A1C is greater than or equal 9%, consider dual therapy.

A1C is greater than or equal 10%, blood glucose is greater than or equal 300 mg/dL
or patient markedly symptomatic, consider combination injectable therapy.

Monotherapy
Dual Therapy
Triple Therapy Lifestyle Management + Metformin + 2 additional agent

Add third agent based on drug-spesific effects and patients factors #


(see Table 8.1)

A1C at target Yes: - Monitor A1C every 3-6 months


After 3 months No: - Assess medication-taking behaviour
Of triple therapy - Consider combination injectable therapy
(see figure 8.2)

Combination Injectable Therapy (see Figure 8.2)

American Diabetes Association. Diabetes Care Volume 41, Supplement 1, January 2018
Combination Injectable therapy for type 2 Diabetes

Initiate Basal Insulin


Usually with metformin +/- other non insulin agent

Start: 10U/day or 0.1-0.2 U/kg/day


Adjust: 10-15% or 2-4 units once or twice weekly to
Reach FBG target
For hypo: Determine & address cause; if no clear
Reason for hypo, ꜜ dose by 4 units or 10-20%

If A1C not controlled, consider combination


injectable therapy

Add 1 rapid-acting insulin Add GLP-1 RA Change to premix insulin twice


injection before largest meals daily (before breakfast & supper
Start: 4 units, or 0.1kg, or 10% basal dose. If A1C If not tolerated or A1C Start: Divide current basal dose into 2/3 AM, 1/3 PM
<8%, consider lower basal by same amount Target not reached or ½ AM, ½ PM
Adjust: increase dose by 1-2 units or 10-15% once or change to 2 injection Adjust: increase dose by 1-2 units or 10-15% once
twice weekly until SMBG target reached insulin regimen or twice weekly until SMBG target reached
For hypo: Determine & address cause; if no clear For hypo: Determine & address cause; if no clear
Reason for hypo, reduce dose by 2-4 units or 10-20% If goals not met, consider Reason for hypo, reduce dose by 2-4 units or 10-20%
changing to injectable
If A1C not controlled, Advance to basal-bolus therapy If A1C not controlled, Advance to 3rd Injection

American Diabetes Association. Diabetes Care Volume 41, Supplement 1, January 2018
Fasting plasma glucose is having high contribution in HbA1c > 8,5%

overall hyperglycaemia
Relative contribution to
100

80 30%
45% 35%
50%
60 70%
(%)

40 70%
65%
50% 55%
20
30%
0
<7.3 7.3–8.4 8.5–9.2 9.3–10.2 >10.2
HbA1c quintiles

FPG PPG

1. Adapted from Monnier et al. Diabetes Care 2003;26:881–5


Combination Injectable therapy for type 2 Diabetes
Add 1 rapid-acting insulin Add GLP-1 RA Change to premix insulin twice
injection before largest meals daily (before breakfast & supper
Start: 4 units, or 0.1kg, or 10% basal dose. If A1C If not tolerated or A1C Start: Divide current basal dose into 2/3 AM, 1/3 PM
<8%, consider lower basal by same amount Target not reached or ½ AM, ½ PM
Adjust: increase dose by 1-2 units or 10-15% once or change to 2 injection Adjust: increase dose by 1-2 units or 10-15% once
twice weekly until SMBG target reached insulin regimen or twice weekly until SMBG target reached
For hypo: Determine & address cause; if no clear For hypo: Determine & address cause; if no clear
Reason for hypo, reduce dose by 2-4 units or 10-20% If goals not met, consider Reason for hypo, reduce dose by 2-4 units or 10-20%
changing to injectable
If A1C not controlled, Advance to basal-bolus therapy If A1C not controlled, Advance to 3rd Injection

Add >2 rapid-acting insulin Change to premix insulin 3 times


injection before meals (basal-bolus) daily (breakfast, lunch & supper)

Start: 4 units, or 0.1kg, or 10% basal dose. If A1C Start: Add additional injection before lunch
<8%, consider lower basal by same amount If goals not met, consider
changing to injectable Adjust: increase dose by 1-2 units or 10-15% once
Adjust: increase dose by 1-2 units or 10-15% once or therapy or twice weekly until SMBG target reached
twice weekly until SMBG target reached
For hypo: Determine & address cause; if no clear
For hypo: Determine & address cause; if no clear Reason for hypo, reduce dose by 2-4 units or 10-20%
Reason for hypo, reduce dose by 2-4 units or 10-20%

American Diabetes Association. Diabetes Care Volume 41, Supplement 1, January 2018
ESW/MAR-17/RTD LVM-2017/001

Outlines

• Prevalence
• Rationale for early initiation
• T2DM management and guideline
• Insulin Levemir® & A1Chieve study
Efficacy of Basal Insulin Focus on Detemir
29

Detemir demonstrate well tolerability profile consistently

Levemir®
2012–2014 tolerability profile
2010–2011 demonstrated over
•SOLVE™
2007–2009
A1chieve™ >17.000 patients7 10 years
TITRATE™ >66,000
2004–2006 of clinical
>224 patients3 patients5 •DIET™8
experience and
Klein et al1 evidence 1–8
PREDICTIVE™ TRANSITION™
6

Philis- >5.604 patients4


Tsimikas et al2

1. Klein O et al. Diab Obes Metab 2007; 9:290-299, 2. Phillis-Tsimikas. Clin Ther 2006;28(10):1569–81, 3. Blonde L et al. Diabetes Obes
Metab. 2009; 11(6):623-631, 4. Hollander et al. Diab Obes Metab 2011; 13:268-275, 5. Home et al. Diabetes Res Clin Pract 2011;94:352–63,
6. Khunti et al. Diabetes Obes Metab. 2012, 7. Hollander PA, Diabetologia 2012; 55 (Suppl. 1): Abstract 939-P
ESW/MAR-17/RTD LVM-2017/001

Insulin Detemir demonstrate less intra-individual day-


to-day variability
NPH NPH NPH

Glargine Glargine Glargine

Detemir Detemir Detemir

30
Adapted from Heise T et al. Diabetes. 2004;53:1614-20.
Home et al. Diabetes Res Clin Pract 2011;94:352–63
A1chieve overview
Insulin Detemir use in Indonesia

2240 patients and 65


investigators were involved in
this study,

Soewondo et al. DRCP 2013. 100;(Suppl 1):S10-S16


ESW/MAR-17/RTD LVM-2017/001

A1chieve study overview and design

• Observational study of people with T2DM in routine clinical practice

Start
Start aa study
study BASELINE
BASELINE INTERIM
INTERIM FINAL
FINAL
insulin
insulin Week
Week 00 Week
Week 12
12 Week
Week 24
24
•• Biphasic
Biphasic insulin
insulin
aspart
aspart 30
30
•• Insulin
Insulin detemir
detemir • Study objectives
•• Insulin
Insulin aspart
aspart • Primary: number of attributed adverse drug
reactions (includes major hypoglycaemia)
• Secondary: other safety and effectiveness
measures
Detemir ± OAD:

Indonesia efficacy results 2.2% Insulin naïve

HbA1c (%) FPG (mg/dl) PPG (mg/dl)


Baseline values 9.5 219 263

24 week 7.3 118 147

*p<0.001
Soewondo et al. DRCP 2013. 100;(Suppl 1):S10-S16
Detemir ± OAD:
Indonesia hypoglycaemia results
Baseline
24 weeks
Overall Major Nocturnal

Insulin naïve Insulin naïve Insulin naïve

No. of pt w/hypo 19 0 1 0 18 0
Percent with at least one
event

Baseline 24 weeks Baseline 24 weeks Baseline 24 weeks

Soewondo et al. DRCP 2013. 100;(Suppl 1):S10-S16


Summary
Insulin naïve participants initiated on Detemir (Indonesia)

Efficacy Safety Other


Baseline
HbA1c Δ HbA1c Δ FPG Δ PPG Hypoglycaemia Weight neutral

IDet 9.5% ↓2.2% ↓101


mg/dL
↓115
mg/dL
0.9*

Significant
Significant improvement
improvement
(p<0.001)
(p<0.001)

*p<0.001
Soewondo et al. DRCP 2013. 100;(Suppl 1):S10-S16
Initiation & titration of basal Insulin
Goal: 3.9–5.0 mmol/L Goal: 4.4–6.1 mmol/L
(70–90 mg/dL)1 (80–110 mg/dL)1

If FPG is If FPG is
+3
units
>5.0 mmol/L (>90 mg/dL) >6.1 mmol/L (>110 mg/dL)

3.9–5.0 mmol/L 0 4.4–6.1 mmol/L


maintain current dose
(70–90 mg/dL) (80–110 mg/dL)

–3
<3.9 mmol/L (<70 mg/dL) units <4.4 mmol/L (<80 mg/dL)

FPG, fasting plasma glucose


1. Blonde et al. Diabetes Obes Metab 2009;11:623–31
ESW/MAR-17/RTD LVM-2017/001

Summary
Indonesia is one of the largest diabetes population

Diabetes is a progressive disease which will lead to the need of insulin


therapy

Insulin therapy is the most efficacious therapy and can reduce HbA1c up to
2,5%

FIX THE FASTING FIRST with BASAL INSULIN

Starting with basal insulin detemir 10 U once daily and titrate based on
patient condition to reach glycemic control

In Indonesia, in real life clinical practice (A1chieve study), Levemir® show


significant improvements in overall glycemic control in terms of HbA1c, FPG,
PPG and patient quality of life

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