Pengantar:

Pengobatan Rasional

Rustamaji

Pusat Studi Farmakologi Klinik dan Kebijakan Obat UGM

2015
Pusat Studi Farmakologi Klinik dan Kebijakan Obat UGM – PT ASKES MAGELANG Magelang, 28 Desember 20111
Homeostasis Kadar Gula darah

2
 Patologi Anatomi Sel Islet Pankreas
DM tipe 2

Sel islet
pankreas
Deposit amyloid pada normal
DM

3
Kriteria Diabetes Melitus

4
Tujuan Terapi

5
Obat Hiperglikemia

6
 A1C 6.5 – 7.5%** A1C 7.6 – 9.0% A1C > 9.0%
Drug Naive Under Treatment

No
Symptom Symptoms
s
Monotherapy Dual Therapy 8

MET † DPP4 1 GLP-1 TZD 2 AGI 3 GLP-1 or DPP4

1 GLP-1
1
or DPP4
*** MET + or TZD 2 INSULIN ± SU 7 INSULIN
2 - 3 Mos. ± Other ± Other
MET + TZD 2
SU or Glinide 4,5 Agent(s) 6 Agent(s) 6
Dual Therapy
GLP-1
± TZD 2
GLP-1 or DPP4 1 2 - 3 Mos.
*** or DPP4 1

MET + TZD 2
Triple Therapy 9
*
May not be appropriate for all patients
Glinide or SU 5 **
For patients with diabetes and A1C < 6.5%,
GLP-1 pharmacologic Rx may be considered
TZD + GLP-1 or DPP4 1 + TZD 2
or DPP4 1 ***
If A1C goal not achieved safely
† Preferred initial agent
Colesevelam MET + GLP-1 AACE/ACE Algorithm for Glycemic Control 1 DPP4 if  PPG and  FPG or GLP-1 if  PPG
MET +
AGI
3 or DPP4 1 7
Committee 2 TZD if metabolic syndrome and/or
+ SU
Cochairpersons: nonalcoholic fatty liver disease (NAFLD)
***
2 - 3 Mos. TZD 2 Helena W. Rodbard, MD, FACP, MACE 3 AGI if  PPG
Paul S. Jellinger, MD, MACE 4 Glinide if  PPG or SU if  FPG
Triple Therapy
*** Zachary T. Bloomgarden, MD, FACE 5 Low-dose secretagogue recommended
2 - 3 Mos. Jaime A. Davidson, MD, FACP, MACE 6 a) Discontinue insulin secretagogue
2
TZD Daniel Einhorn, MD, FACP, FACE with multidose insulin
MET + Alan J. Garber, MD, PhD, FACE b) Can use pramlintide with prandial
GLP-1 or + James R. Gavin III, MD, PhD insulin
DPP4 1 Glinide or SU 4,7 INSULIN George Grunberger, MD, FACP, FACE
7 Decrease secretagogue by 50% when added to GLP-
Yehuda Handelsman, MD, FACP, FACE
2 - 3 Mos.*** ± Other
Edward S. Horton, MD, FACE
1 or DPP-4
Agent(s) 6 Harold Lebovitz, MD, FACE 8 If A1C < 8.5%, combination Rx with agents that
Philip Levy, MD, MACE cause hypoglycemia should be used with caution
INSULIN Etie S. Moghissi, MD, FACP, FACE 9 If A1C > 8.5%, in patients on Dual Therapy,
Stanley S. Schwartz, MD, FACE insulin should be considered
± Other
Pusat Studi
Agent(s)Farmakologi
6 Klinik dan Kebijakan Obat UGM – PT ASKES MAGELANG Magelang, 28 Desember 20111
Available at www.aace.com/pub
© AACE December 2009 Update. May not be reproduced in any form without express written permission from AACE
Perdandingan Obat Diabetes

8
Perbandingan Obat Antidiabetika Oral

9
Perbandingan Obat Antidiabetika parenteral

10
Kenaikan HbA1c setelah beberapa tahun
terapi

8.0
ADOPT
ADOPT study
study
7.6

7.2

6.8
HbA1c (%)

6.4

6.0
0
Rosiglitazone
Metformin
Glybenclamide

0 1 2 3 4 5
Time (Years)

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

11
Insulin

12
 Early Addition of Insulin
Can Optimize Glycemic Control

50 p=0.011 Early addition of insulin

Proportion of Patients with HbA1c

when OAD is inadequate

can improve glycemic control
<7% at 6 Years (%)

without weight gain

25 or hypoglycemia

0
n=242 n=245 n=339
SU = sulfonylurea
e
al

n
lon
on

u li
I ns
nti

nA
nve

u li

±
SU
I ns
Co

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

13
14
 Tahap 1 Tahap 2 Tahap 3

Gaya hidup +
Gaya hidup +
Saat diagnosis: Metformin +
Metformin +
Gaya hidup Insulin basal
Insulin intensif
+
Metformin Gaya hidup +
Metformin +
Well validated core
therapies Sulfonilurea

Gaya hidup +
Gaya hidup +
Metformin +
Metformin +
Pioglitazon +
Pioglitazon
sulfonilurea

Gaya hidup + Gaya hidup +

Less well validated Metformin + Metformin + insulin
core therapies
GLP-1 agonis basal
15
Nathan DM et al, Diabetes Care 32:193–203, 2009
 Sejarah Perkembangan
insulin

 1921 : penemuan insulin

 s/d 1983 : era insulin hewan
Menggunakan ekstrak pankreas hewan (sapi / babi)
 1983 : era Human insulin
Menggunakan 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

16
Pembagian Insulin menurut masa kerjanya

17
Profil farmakokinetika Insulin

18
 Profil Farmakokinetika
Human Insulin vs normal insulin

Period of unwanted
hyperglycemia
Normal insulin secretion
at mealtime
Change in serum insulin

Human insulin

Period of unwanted
hypoglycemia

Human Insulin 
Baseline
disuntikkan 30 menit
level
sebelum makan

Time (h)
19
SC injection
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 (Levemir) Prandial Insulin

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

28