Analogue Insulin, The new tools to challenges Diabetes

Presentation Point of View

1. Rationality of Insulin Therapy for Type 2 DM2. What is Analogue Insulin? 3. How & strategy of Insulin treatment ?4. Barrier of using insulin5. Take Home Message

Normal islet cell

Deposition of amyloidin T2DM

Natural History of Type 2 DM

Insulin

OAD : Kegagalan sekunder sesudah beberapa tahun

ADOPT: Kahn SE et al. N Engl J Med 2006;355:2427-43.

8.0

7.6

7.2

6.8

6.4

6.00

0 1 2 3 4 5

Time (Years)Time (Years)

HbAHbA

1c1c (%

) (%

)

RosiglitazoneMetforminGlybenclamide

ADOPT studyADOPT studyADOPT studyADOPT study

UKPDS 57: Adapted from Wright A et al. Diabetes Care 2002;25:330-6.

Early Addition of Insulin Can Optimize Glycemic Control

Conv

entio

nal

Conv

entio

nal

Insu

lin A

lone

Insu

lin A

lone

SU

SU ± ±

Insu

linIn

sulin

5050

2525

00

pp=0.011=0.011

Prop

ortio

n of

Pati

ents

with

Pr

opor

tion

of P

atien

ts w

ith H

bAHbA

1c1c

<7%

<7%

at 6

Yea

rs (%

) a

t 6 Y

ears

(%)

n=242n=242 n=245n=245 n=339n=339

Early addition of insulin Early addition of insulin when OAD is inadequate when OAD is inadequate can improve glycemic control can improve glycemic control without weight gain without weight gain or hypoglycemiaor hypoglycemia

SU = sulfonylureaSU = sulfonylurea

Saat diagnosis:

Gaya hidup

+

Metformin

Gaya hidup +

Metformin +

Insulin basal

Gaya hidup +

Metformin +

Sulfonilurea

Gaya hidup +

Metformin +

Insulin intensif

Gaya hidup +

Metformin +

Pioglitazon

Gaya hidup +

Metformin +

GLP-1 agonis

Gaya hidup +

Metformin +

Pioglitazon + sulfonilurea

Gaya hidup +

Metformin +

Basal insulin

Well validated core therapies

Less well validated core

therapies

Tahap 1 Tahap 2 Tahap 3

Nathan DM et al, Diabetes Care 32:193–203, 2009

Tahap 2

Presentation Point of View

1. Rationality of Insulin Therapy for Type 2 DM2. What is Analogue Insulin? 3. How & Strategy of Insulin Treatment4. Barrier of using insulin5. Take Home Message

Sejarah Perkembanganinsulin

1921 : penemuan insulin s/d 1983 : era insulin hewan

Menggunakan ekstrak pankreas hewan (sapi / babi)

1983 : era Human insulinMenggunakan rDNA manusia untuk

menghasilkan insulin 1999 : era insulin modern (analog) dimulai

Menggunakan teknologi bioengineering untuk memodifikasi rantai DNA human insulin untuk membuat insulin baru yang lebih baik dalam hal farmakologi

Saccharomyces cerevisiae

MIXTARD - PREMIX

INSULATARD – NPH - INTERMEDIATE

ACTRAPID – SHORT ACTING

ANALOG INSULINHUMAN INSULIN NOVO NORDISKHUMAN INSULIN NOVO NORDISK

Actrapid/Mixtard/Insulatard Novolet

akan habis stoknya (discontinue)

per bulan juni 2010

Kelemahan Human Insulin (Actrapid/Mixtard)

Time (h)

Baseline

level

Human insulin

SC injection

Normal insulin secretionat mealtime

Ch

an

ge in

seru

m in

sulin

Period of unwanted hypoglycemia

Period of unwanted hyperglycemia

Human Insulin HARUS disuntikkan 30 menit

sebelum makan

Kelemahan Human Insulin Insulatard (NPH)

tidak bekerja 24 jam

Memiliki puncak risiko nokturnal hipo sangat tinggi

Absorbsi insulin bervariasi, bahkandi pasien yang sama kendali gula darahtidak terprediksi

NOVOMIX - PREMIX

LEVEMIR -LONG ACTING ANALOG

NOVORAPID - RAPID ACTING

ANALOG INSULINANALOG INSULIN NOVO NORDISKANALOG INSULIN NOVO NORDISK

Structural Design Human Insulin

Thr

Glu

Lys

ValPhe

Asn

Glu

Leu

Gln

Tyr

LeuSerCysIleSerCys

Cys

Gln

Glu

Val

Ile

GlyTyr

CysAsn

Lys

ThrTyr

Phe Phe ArgGlyGlu

GlyCys

Val

Leu

Tyr

Leu

Ala

Val

Leu

His

SerGly

Cys

Asn Gln LeuHisB1

A21

A1

B29

C14 fatty acid chain

(Myristic acid)

Thr

Pro

Asp

Levemir (Insulin Detemir)NovoRapid (Insulin Aspart)

Pro