Levemir IDI UNMU 2014

8/11/2019 Levemir IDI UNMU 2014

1/46

Presentation title

Insulin Initiation :

When We should Start with Basal Insuli

Dr Ali Santosa SPPD


2/46

AGENDA

Diabetes is a progressive disease and is increasing

in prevalence The mapping of insulin treatment based recent guidelines

Insulin Initiation, when we should start with basal insulin

Conclusion


3/46

20102000171 million1

2030

552 millio

2011

366 million2

Diabetes is a global diseaseEstimated global prevalence of diabetes

1. Wild. Diabetes Care. 2004. 27:1047-1053.2. International Diabetes Federation.IDF Diabetes Atlas. Fifth Edition. 2011


4/46


5/46

Normal

The progressive nature oftype 2 diabetes

Impairedglucosetolerance

Type 2diabetes

Fasting plasma glucose

Insulin sensitivityInsulin secretion

Insulinsensitive

Normal insulinsecretion

Normoglycaemia

Late type 2diabetescomplications

Adapted from Bailey CJ et al. Int J Cl

Groo LC. Diabetes Obes Meta

Insulin resistance


6/46

Insulin and Glucagon Response to a LargeCarbohydrate Meal in Type 2 Diabetes

Insulin

(U/ml)

Glucagon

(g/ml)

Glucose

(mg/100

ml)

*Insulin measured in five patientsAdapted from Mller WA et al N Engl J Med1970;283:109115.

Type 2 diabetes mellitus (n=12)*Nondiabetic controls (n=11)

150

0140

90

360

80

240

60

Time (minutes)

306090

120

110

270300330

100110120130

Meal

Nonsuppressed glucagon

0 60 120 180

Depressed/delayed insulin respo


7/46


8/46

100

75

50

25

UKPDS : Progressive Deterioration of -Cell Functio

Years from Diagnosis

Adapted fromLebovitz H. Diabetes Review 1999;7

BetaCellF

unction(%)

-12 10 -6 -2 0 2 6 10

Th/Expectation withintensive treatment

Facts

Why ?

ETIOLOGY OF BETA CELL FAILURE IN T2DM

Age5. Incretin

Effect

Genetic(TCF 7L2)

4. Amyloid

Deposition

1. Glucose

toxicity

2. Lipotoxicity

FFA

3. Insulin

Resistanc

Beta-cell

Failure

De Fronzo Banting Lecture (submitted ADA Meeting 2008 /Claude Bernard Awar


9/46


10/46

-Cell Function Continues to Decline

Regardless of Intervention in T2DM

T2DM = type 2 diabetes mellitus

*-cell function measured by homeostasis model assessment (HOMA)

0

20

40

60

80

100

5 4 3 2 1 0 1 2 3 4

Years Since Diagnosis

-CellFunction(%)*

Progressive loss of -cell function

occurs prior to diagnosisMetformin

Diet (n = 1

Sulfonylur


11/46

AGENDA




Conclusion


12/46

Treat T2DM early for long-term benefits1

Long-term benefits in reducing cardiovascular risk can be achievgood control from diagnosis1

-14%

-37%

-21%

Myocardial infarction

Microvascular complic

Death related to diabe

Each HbA1cpercentage

point

reductioncounts3

HbA1c-1%

1. Holman, et al. NEJM 2008;359:1577892. UKPDS 6. Diabetes Res1990;13(1):1-113. Stratton, et al. BMJ2000;321(7258):405-12

50% of patients with T2DM with complicatalready have them at diagnosis2
http://images.google.dk/imgres?imgurl=http://www.buytaert.net/cache/images-miscellaneous-2006-eye-500x500.jpg&imgrefurl=http://buytaert.net/tag/photography?page=5&h=333&w=500&sz=200&hl=da&start=22&tbnid=XP6aV9751NDPgM:&tbnh=87&tbnw=130&prev=/images?q=eye&start=20&gbv=2&ndsp=20&svnum=10&hl=da&sa=Nhttp://images.google.dk/imgres?imgurl=http://www.barco.com/barcoview/downloads/BarcoVoxar3DCardia.jpg&imgrefurl=http://www.barco.com/corporate/en/pressreleases/show.asp?index=1662&h=680&w=680&sz=57&hl=da&start=7&tbnid=Arh6Yt46rdsIOM:&tbnh=139&tbnw=139&prev=/images?q=cardiac&gbv=2&svnum=10&hl=da


13/46

What is the optimal target HbA1clevel?

Goals of optimum HbA1clevels:

Good glycaemic control

Minimise development and progression of microvascularand macrovascular complications

HbA1c


14/46

AGENDA




Conclusion


15/46

Gaya hidup +

Metformin+Pioglitazon

Gaya hidup +

Metformin+

GLP-1 agonis

Gaya hidup +

Metformin+Pioglitazon +

sulfonilurea

Gaya hidup +

Metformin+

Insulin Basal

Less well validatedtherapies

Saat diagnosis:

Gaya hidup

+Metformin

Gaya hidup +

Metformin+

Insulin Basal

Gaya hidup +

Metformin+

SulfonilureaWell validated

therapies

Tahap 1 Tahap 2 ADA-EASD 2009


16/46

Insulin remains the most efficacious glucoselowering agent

Decrease in HbA1c: Potency of monotherapy

HbA1c

%

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

CHOOSING INSULIN EARLIERFOR BETTER EFFICACY


17/46

Choosing Insulin

for your Patient?


18/46

Insulin can be initiated anytim

Inadequate

Lifestyle+1 OAD

+2 OAD

+3 O

InitiateInsulin

Traditionally, insulin had been reserved as the last line o

Considering the benefits of normal glycemic status,

insulin can be initiated earlier, as soon as is required.

1. Fasting BG > 250 mg/dL

2. Random BG > 300 mg/d

3. Hb A1c > 10 %

4. Weight loss ++

5. Ketonuria

Indication:


19/46


20/46

Once daily injection, anytime injection but in same time per each day

How to start basal insulin

Titrate the dose every3 days, if FPG >110mg/dl increased 3units and if FPG < 80mg/dl decrease 3units

Start with basalinsulin (InsulinDetemir) 10 U or 0,1-0,2 U per Kg BB

TitrateStart

Meneghini L et al. Diabetes Obes Metab, 9, 2007, 902-913


21/46

How to titrate basal insulin

Levemir Dose Titration Guidelines:3-0-3 Algorithm

FPG>110 mg/dL + 3 U

80-110 mg/dL 0

FPG


22/46

Levemirprovide optimal HbA1c reducti

Reference: 1. Soewondo P et al. Clinical experience with insulin detemir: Result from the Indonesian cohort of the international A1chieve study. Diabetes Res Clin Pract;suppl.S192013) S47-S53.


23/46


24/46

Levemir reduces nocturnal hypoglycaemia by up65% compared to NPH

Phillis-Tsimikas. Clin Ther 2006;28(10):156981; Riddle et al 2003. Diabetes Care; 26 (11): 3080-

6; Asakura T et al, 2008. Expert Opin Pharmacother; 10 (9): 1-5; Hanel H et al 2008. J DiabetesSci Technol; 2 (3): 478-81

In

In

In

RelativeRisk

Riddleet al., 2003 Phillis-Tsimikas et al., 2006

-29% -44% -53% -65%

NPH vs. glargine NPH vs. detemir

Levemir Demonstrated More Consistent Insulin A


25/46

LevemirDemonstrated More Consistent Insulin A54 Type 1 Diabetic Subjects Randomly Assigned to receive one type of Idose 0.4 u/kg, 4 Different Times

Adapted from Heise T et al. Diabetes. 2004;53:1614-20.

NPH NPH

Glargine Glargine

Detemir Detemir


26/46

Levemir is approved in pregnancy and childrenyears

EMEA, FDA and BPOM has been approved Levemirin diabetes

(B category)and children 2 years


27/46


28/46

Observational study of people with T2DM in

routine clinical practice

Study objectives Primary: number of attributed adreactions (includes major hypogly

Secondary: other safety and effemeasures

BASELINEWeek 0

INTERIMWeek 12

FW

Start a studyinsulin

Biphasic insulinaspart 30

Insulin detemir Insulin aspart

A1chieve study overview and desig


29/46

HbA1c(%) FPG (mg/dl) PPG

Baseline values 9.5 219 263

n 147 317 295

Levemir OAD:Indonesia efficacy results

-101*

-

-120

-100

-80

-2.2*

-3.0

-2.0

-1.0

0.0

Changefromb

aselineto

week

24

*p


30/46

Levemir OAD:Indonesia hypoglycaemia results

5,10

0,30

4,80

0,00 0,00 0,000,0

1,0

2,0

3,0

4,0

5,0

6,0

Overall Major Nocturnal

Insulin nave Insulin nave Insulin nave

No. of pt w/hypo 19 0 1 0 18 0

Percentwithatlea

stoneevent


31/46

AGENDA

Diabetes is a progressive disease and is increasingin prevalence

The mapping of insulin treatment based recent guidelines


Conclusion


32/46


33/46

The association between post cha


34/46

The association between post-chaglycaemia and mortality

Adjusted for age, centre, sex, cholesterol, BMI, SBP, smoking

2.5

0

Hazardratio

formortality

2.0

1.5

1.0

0.5

2.5

0

2.0

1.5

1.0

0.5

>7.87-7.7

6.1-6.9


35/46


36/46

Plasma Insulin

Normal 24 Hr Insulin Profiles & Bd prem

Bd premix Bd premix

NovoMix 30 provides better


37/46

NovoMix 30 provides betterHbA1c reduction than Mixtard 30

65%

35%

30%

13.3%

0%

10%

20%

30%

40%

50%

60%

70%

ADA target (HbA1c < 7.0%) AACE target (HbA1c > 6.5%)

Proporti

onsachieving

HbA1ctar

gets

N

M

p


38/46

Low risk of major hypoglycemia

Boehm et al. Eur J Interna

0

2

4

6

8

10

12

1st year 2nd year

Year of study

Patient

swithatleastonem

ajor

episode(%)

p= NS

p= 0.04

BIHu

5%

8%

0%

10%

Two Ye

Long-te


39/46

Basal-Bolus Strategy as IdeConceptLevemir-Novorapid

Date

The Basal/Basal Plus strategy for T2DM


40/46

Stepwise intensification of treatment for continuity o

Progressive deterioration of -cell function

Lifestyle changes

Oral agents

BasalAdd basal insulin and titra

Basal Add prandial insul

HbA1cabove target

FBG above target

HbA1cabove target

BAd

d

FBG at target

HbA1cabove target

Adapted from Raccah D, et al. Diabetes Metab Res Rev 2007 (in press).

Date


41/46

Starting Basal-Bolus Program

In general

Calculate Total Daily Dose by using 0.5to Patient Body Weight (kg)

Example :

Patients Body weight : 60 kg

Total daily dose is : 0.5 x 60 kg : 30 iu

Use 60% of Total Daily Dose as Prandi(divided by 3) and 40% of TDD as Bas

PERKENI, Petunjuk praktis terapi insulin pada pasien DM, 2007


42/46


43/46

Suntikkan 10 iu Levemir sekali sebelum tidur. Adosisnya (+3 atau 3) setiap 3 hari sd GDP men

Tambahkan Injeksi NovoRapid di setiap makan (2-

t k d lik G l d h 2 j PP


44/46

Time of day (hours)

400

300

200

100

006.00 06.0010.00 14.00 18.00 22.00 02.00

Plasm

aglucose

(mg/dl)

NormalMeal Meal Meal

2

1

1

5

0

dosisnya (+3 atau -3) setiap 3 hari sd. GDP men

target GDP 80-110 mg/dL (Perkeni 2006)

Hyperglycaemia due to an increase in fasting glucose

T2DM

untuk mengendalikan Gula darah 2 jam PP menca

< 180 mg/dL (Perkeni 2006)BasalBolus Concept dengan Levemir -

NovoRapid

Profile T2

Conclusion


45/46

Conclusion

Diabetes is a progressive disease that is increasing in prevalence world

Starting with basal insulin detemir is easy way to reach better glycontrol

In Indonesia, in real life clinical practice (A1chieve study) Levemisignificant improvements in overall glycaemic control in terms of and PPG.


46/46

Levemir IDI UNMU 2014

Documents

Transcript of Levemir IDI UNMU 2014