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Pengobatan Rasional
Rustamaji

Pusat Studi Farmakologi Klinik dan Kebijakan Obat UGM

Pusat Studi Farmakologi Klinik dan Kebijakan Obat UGM PT ASKES MAGELANG
2015
28 Desember 20111

Magelang,

Homeostasis Kadar Gula

darah

Patologi Anatomi Sel Islet Pankreas

DM tipe 2

Deposit amyloid
pada DM

Sel islet
pankreas
normal

Kriteria Diabetes Melitus

Tujuan Terapi

Obat Hiperglikemia

A1C 6.5
7.5%**

A1C 7.6 9.0%

Monotherapy
MET

DPP4 1

GLP-1

TZD 2

Dual Therapy
AGI 3

2 - 3 Mos.***

MET

MET

TZD

AGI

2 - 3 Mos.***
Triple Therapy
TZD 2

Glinide or SU 4,7

2 - 3 Mos.***
INSULIN
Other
PusatAgent(s)
Studi Farmakologi

28 Desember 20111
6

or DPP4 1
MET

SU 7

TZD 2

2 - 3 Mos.***

INSULIN
Other
Agent(s)
6

TZD 2
May
not1be appropriate
for all
or
DPP4

patients
For patients with diabetes and A1C <
6.5%, pharmacologic Rx may be
Therapy 9
considered
***
If A1C goal not achieved safely
GLP-1
2

Preferred initial agent

+
TZD
or DPP4 1
1 DPP4 if PPG and FPG or GLP-1 if
PPG
GLP-1
AACE/ACE Algorithm for
2 TZD if metabolic syndrome and/or
Glycemic Control Committee
or DPP4 1
nonalcoholic fatty liver disease
+ SU 7
(NAFLD)
Cochairpersons:
Helena W. Rodbard, MD, FACP,
3 AGI if PPG
TZD 2
MACE
4 Glinide if PPG or SU if FPG
Paul S. Jellinger, MD, MACE
5 Low-dose secretagogue
***
2 - 3 Mos.
recommended
Zachary T. Bloomgarden, MD, FACE
Jaime A. Davidson, MD, FACP, MACE
6 a)
Discontinue insulin
Daniel Einhorn, MD, FACP, FACE
secretagogue
Alan J. Garber, MD, PhD, FACE
with multidose insulin
INSULIN
James R. Gavin III, MD, PhD
b)
Can use pramlintide with
Other
George Grunberger, MD, FACP, FACE
prandial insulin
Agent(s)
Yehuda Handelsman, MD, FACP, FACE
7 Decrease secretagogue by 50% when
6
Edward S. Horton, MD, FACE
added to GLP-1 or DPP-4
Harold Lebovitz, MD, FACE
8 If A1C < 8.5%, combination Rx with
Philip Levy, MD, MACE
agents that cause hypoglycemia
Etie S. Moghissi, MD, FACP, FACE
should be used with caution
Stanley S. Schwartz, MD, FACE
9 If A1C > 8.5%, in patients on Dual
Therapy, Available at www.aace.com/pub
AACE December 2009 Update. May not be reproduced ininsulin
any form
without
written permission
should
beexpress
considered
from AACE
**

Triple

GLP-1 or DPP4 1
Colesevelam

MET +
GLP-1 or
DPP4 1

or TZD 2

INSULIN
Other
Agent(s)

GLP-1

Glinide or SU 5
TZD

GLP-1

SU or Glinide 4,5

GLP-1 or DPP4 1

No
Symptom Symptoms
s

GLP-1 or DPP4

Dual Therapy

MET

A1C > 9.0%

Drug Naive Under Treatment

MET

Klinik dan Kebijakan Obat UGM PT ASKES MAGELANG

Magelang,

Perdandingan Obat
Diabetes

Perbandingan Obat Antidiabetika Oral

Perbandingan Obat Antidiabetika

parenteral

10

Kenaikan HbA1c setelah beberapa

tahun terapi
8.0

ADOPT
ADOPT
study
study

7.6

HbA1c (%)

7.2
6.8
6.4
6.0
0

Rosiglitazone
Metformin
Glybenclamide

Time (Years)

ADOPT: Kahn SE et al. N Engl J Med 2006;355:242711

43.

Insulin

12

p=0.01
1

50

Early addition of insulin

when OAD is inadequate
can improve glycemic
control

25

without weight gain

n=339
uli
n

SU = sulfonylurea

SU

Ins

n=245

Ins
uli
n

n=242
en
tio
na
l

Alo
ne

or hypoglycemia

Co
nv

Proportion of Patients with

HbA1c <7% at 6 Years (%)

Early Addition of Insulin

Can Optimize Glycemic Control

UKPDS 57: Adapted from Wright A et al. Diabetes Care

13
2002;25:330-6.

14

Tahap 1

Tahap 2

Tahap 3

Gaya hidup +
Saat
diagnosis:

Gaya
hidup
+
Well
validated
Metformin
core therapies

Metformin +

Metformin +

Insulin
basal

Insulin
intensif

Gaya hidup +
Metformin +

Sulfonilurea
Gaya hidup +
Metformin +

Less well
validated core
therapies

Gaya hidup +

Gaya hidup +
Metformin +

Pioglitazon

Pioglitazon +
sulfonilurea

Gaya hidup +

Gaya hidup +

Metformin +

Metformin +

GLP-1
agonis

insulin basal
15

Nathan DM et al, Diabetes Care 32:193203, 2009

Sejarah Perkembangan
insulin

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

1999

/ babi)

1983

Menggunakan ekstrak pankreas hewan (sapi

: era Human insulin

Menggunakan rDNA manusia untuk

menghasilkan insulin

: 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
16

Pembagian Insulin menurut masa

kerjanya

17

Profil farmakokinetika
Insulin

18

Profil Farmakokinetika
Human Insulin vs normal insulin

Period of unwanted
hyperglycemia

Change in serum insulin

Normal insulin secretion

at mealtime
Human insulin
Period of unwanted
hypoglycemia

Human Insulin
Baseline
disuntikkan
30 menit
sebelum level
makan

Time (h)
SC injection

19

Change in serum insulin

A More Physiologic Insulin

Normal insulin
secretion at mealtime
Insulin analog

Baseline
Level

Time (h)
SC injection
20

Glycemic Control: Recommended goals

Measurement

Normal

IDF1

ADA/EASD2

AACE3

PERKENI

A1c*

<6%

<6.5%

<7%

<6.5%

<6.5%

Fasting Gluc

<100

<110

90-130

<110

80-110

PP (2h) Gluc

<140

<155

<180

<140

80-145

Realistic Target: Lowest A1c possible without unacceptable adverse effects

IDF = International Diabetes Federation
ADA = American Diabetes Association.
AACE = American Association of Clinical Endocrinology
1. Global guideline for type 2 diabetes clinical guidelines taskforce (Brussels: IDF,2005)
2. Nathan DM et al. Diabetologia 2006;49:1711-21.
3. http://www.aace.com/pub/odimplementation/roadmap.pdf
21

Penggunaan Insulin
Insulin had been reserved as the last line of therapy
Considering the benefits of normal glycemic status,
insulin can be initiated earlier, as soon as is required.

Inadequate
Lifestyle

1 OAD

2 OAD

3 OAD

insulin
Indication: Permanent

Not permanent

T1DM

Infection

OAD failure

Pregnancy

OAD Contra Indication

Hospitalized

Diabetic Ketoacidosis

Perioperative

22

Basic Recommendation
1. If fasting blood glucose is elevated, start for
basal insulin
with long acting insulin (Levemir)
2. If prandial blood glucose is elevated, start for
prandial /bolus insulin with rapid acting insulin
3. If fasting and post prandial are elevated :
- Oral agent with basal insulin
- premix insulin
- basal/bolus as in multiple daily injection (MDI)
23

Treatment Based on Type of Hyperglycemia

BASAL PRANDIAL CONCEPT
Fasting

Hyperglycemia

Prandial

Treat fasting hyperglyc. first

Continue oral agent
SMBG is important

Basal Insulin

Prandial Insulin

(Levemir)

24

PENDAPAT PASIEN YANG MENJADI

KENDALA TERAPI INSULIN (1)
1.Sekali mulai terapi insulin, tidak bisa di stop lagi
(Persepsi yang salah, seperti kecanduan obat )
Berikan insulin dengan masa perkenalan jangka pendek :

2. Suntik insulin sangat merepotkan

( Pasien merasa tidak sanggup suntik sendiri)
Demonstrasikan kepada pasien cara melakukan suntikan
insulin
Sesuai indikasi, pilihlah insulin 1x /hari untuk mengurangi
ketidaknyamanan

Polonsky WH, Jackson RA. Clinical Diabetes 2004;22:147-50.

25

PENDAPAT PASIEN YANG

MENJADI KENDALA TERAPI
INSULIN (2)

3. Kegagalan terapi adalah kesalahan saya

(suntikan insulin sebagai hukuman karena kegagalan pribadi)

Jelaskan bahwa insulin diperlukan karena perjalanan penyakit
DM, bukan karena kegagalan pasien mengelola penyakitnya)

4. Famili saya disuntik insulin sebelum diamputasi

kakinya
(Insulin diberikan bila Diabetes sudah berat)

Jelaskan bahwa suatu saat insulin diperlukan karena perjalanan

alamiah penyakit DM

5. Saya tidak berani suntik insulin sendiri, karena

nyeri..!

(Ketakutan terhadap suntik insulin)

Berikan dorongan untuk melakukan penyuntikan sendiri
Polonsky WH, Jackson RA. Clinical Diabetes 2004;22:147-50.
26

HIPOGLIKEMIA

27

Terima Kasih

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