Peran Anti Diabetik Oral dan Insulin

pada Managemen Diabetes Tipe-2

Penatalaksanaan Diabetes
 Terapi obat-obatan
1. Obat Hipoglikemik Oral (OHO)
 Insulin sensitisizer : biguanid ( metformin ), thiazolidinedione
(pioglitazone)
 Insulin secretagogue :
 Sulfonylurea :glibenclamide, glimepiride
 Non-sulfonylurea : nateglinide and repaglinide
 Glucosidase inhibitor ( acarbose )
 Incretin dan DPP-4 inhibitor

2. Insulin
Mekanisme kerja Obat Hipoglikemik Oral

Agents Site of action MOA

Sulphonylurea Insulin
secretion
Incretin Glucagon and insulin

Biguanides Glucose
Thiazolidinediones production 

-glucosidase
- Slow carbohydrate
inhibitors digestion

Thiazolidinediones Peripheral insulin

(biguanides) sensitivity

DeFronzo. Ann Intern Med 1999;131:281-303

 1. Metformin (biguanid)

Derivat guanidin, dari Gallega officinalis

Menurunkan produksi glukosa di hati

Menurunkan kadar glukosa darah puasa

Mempunyai efek terhadap sensitivitas otot terhadap insulin

Biguanides
Act by inhibiting liver
gluconeogenesis &
increasing insulin
sensitivity in other
tissues

Metformin is not
metabolized, but
excreted intact in 2-5 h
 Mekanisme kerja Metformin

Pancreas

Impaired
Insulin secretion

produksi glukosa Decreased

meningkat glucose
Hyperglycaemia uptake

Liver – + Muscle

Metformin
 Multiple Action Mechanisms of Metformin

Metformin Insulin Glucose

Plasma membrane
surface charge

Plasma membrane
fluidity, plasticity
of receptors &
transporters
Insulin-stimulated
receptor phosphorylation
& kinase activity
Glucose transporter
translocation and activation
Enzymatic effects on Glucose
metabolic pathways metabolism
and storage
 Efek pada RESITENSI INSULIN

SEBELUM metformin
insulin

glukosa
glucose
glucose
transporter
transporter

SESUDAH metformin
 Metformin:
multiple mechanisms for CVD protection
Metformin addresses CV risk by a range of mechanisms

Improved
• Insulin sensitivity
• Glycaemia
• Fibrinolysis
• Microcirculation
• Endothelial function
• Obesity management
Reduced
• Hypertriglyceridaemia
• AGE formation
• Intravascular thrombus
• Oxidative stress
• Atherogenesis
• Dyslipidaemia

Reduced cardiovascular risk

 Metformin
Dosis awal: 500 mg OD dosis dinaikkan , 1-2
minggu
Dosis maksimal 2.250 mg/ tercapai dalam 2-3 bulan,
frekuensi harus 2 atau 3 kali sehari.
Jika target terapi belum tercapai, tambahkan obat dari
kelas lain
Target harus tercapai dalam 6 bulan
 Biguanides/Metformin
Kontra indikasi
• Gagal ginjal
• Ggn fungsi hati
• Gagal jantung
• Gangguan GITyang berat
Keuntungan
• Tidak menyebabkan hipoglikemia jika diberikan sebagai obat tunggal
• Tidak meningkatkan berat badan, bahkan berperan terhadap menurunkan
berat badan.
Efek samping:

GIT ( mual, abdominal discomfort diarrhea dan kemungkinan konstipasi)

asidosis laktat

Slides current until 2008

Peningkatan atau penambahan
Jika target terapi belum tercapai dalam 2-3 bulan,
harus ditambahkan obat dari kelas lain
Target harus tercapai dalam 6 bulan
Insulin harus ditambahkan jika mungkin untuk
mencapai target terapi.
Golongan Generik Merk mg/tab Dosis Dosis Lama Frek.
Harian Awal Kerja / hari

Biguanid Metformin Glucophage 500-850 250-3000 - 6-8 1-3

Diabex
Glumin
Mechanism of Glucose-Mediated Insulin Secretion

GLUT-2 Sulfonylurea/non
Glucokinase
Glucokinase sulfonylurea
Glucose
Glucose
Glucose G-6-P
G-6-P
Metabolism
Metabolism
Signal
Signal (S)
(S) ATP
ATP
ADP K
K++
ADP ATP
ATP

Secretory
Secretory Depolarization
Granules
Granules Ca
Ca++
++

Ca++

Insulin Secretion
 Sulfonilurea

• Meningkatkan sekresi insulin

• Ada banyak jenis

Efek samping
• Hipoglikemia
• Stimulasi nafsu makan dan meningkatkan berat badan
• Mual, rasa penuh di perut, dan rasa terbakar di ulu hati
• Kadang –kadang timbul rash
• pembengkakan

Slides current until 2008

 Repaglinide/ Nateglinide
Nonsulphonylurea insulin secretagogues

Mechanism:
Closes ATP-sensitive potassium channels
on ß-cells.
Binds to a site distinctly separate from the
sulphonylureas.
 Meglitinide Analogs
Bind to ß cells via SU receptor
Rapid absorption, metabolism & clearance, T 1/2 < 1 h

After www.bentham.org/sample-issues/cmc9-1/kecskemeti/fig8.gif
 Nateglinide/Repaglinide

K
K++

140
140
kDa
kDa
65
65
kDa
kDa
Sulphonylurea Receptor

K
KATP channel
ATP channel
K
K++

Quicker attachment
Earlier Detachment
Insulin Levels in
Nateglinide/Repaglinide
Repaglinide
Traditional
Sulphonylurea
Advantages of
Nateglinide/Repaglinide
Flexibility in mealtime dosing
No significant increase in bodyweight
Can be utillised in mild to moderate
renal failure
Nateglinide: approved in hepatic failure
Dosage: Repaglinide:
0.5mg/1mg/2mg/4mg per dose per
meal
Nateglinide: 60mg/120mg per dose per
meal
Lower incidence of hypoglycemia
◦ elderly patients in whom hypoglycaemia is a concern

◦ patients with kidney failure or mild hepatic impairment

◦ patients taking low-dose sulphonylureas who encounter

problems with hypoglycaemia

Useful
◦ Patients with irregular Situations
meal patterns

Int J Clin Pract. 2003 Jul-Aug;57(6):535-41.

Disadvantages of Metaglinide
derivatives

Works predominantly in mild

hyperglycaemia

Less convincing with fasting

hyperglycaemia
 Stimulate
insulin
release from
ß cells via
binding to
the SU
receptor =
K+ATP
channel
Mostly long
metabolic
Sulfonylureas T1/2
After www.bentham.org/sample-issues/cmc9-1/kecskemeti/fig-1.gif
Glimepiride
Modes of action: Glimepiride
Most Sulphonylureas K
K++
Glimepiride

140
140  -- cell
cell
Glimepiride kDa
kDa membrane
membrane
65
65
Sulphonylurea kDa
kDa
Receptor
K
KATP channel
ATP channel
K
K++
GLUT-4
So What ??

65kDa Component absent in Cardiovascular System

Safer to use in patients with a higher cardiovascular risk
 Type II Diabetes and Exercise
Improvement in insulin Sensitivity:

Activates intracellular GLUT-4 glucose transporters

(Effect lost in 48 hours)
Conventional Sulphonylureas:
failure of insulin suppression

Hypoglycaemia / overeating in the morning/ weight gain.

 Advantages of Glimepiride
(Over other sulphonylureas)

Single daily dosing

Comparable hypoglycaemic side effect profile
to glipizide
Safer in the presence of cardiac disease (SU-
receptor –ve)
Peripheral action conserves endogenous
insulin
Safer to use in the physically active
 Class Generic Brand mg/tab Daily dose Initial Duration Frequency
dose of action /day
Sulfonyl Glibenclamide Daonil 2.5 , 5 2.5 – 15 2.5 12-24 1-2
urea Euglucon
Glipizide Minidiab 5, 10 5-20 5 10-16 1-2
Glucotrol XL
Gliclazide Diamicron 80 80-240 80 10-20 1-2
Gliquidone Glurenorm 30 30-120 30 - 1-3
Glimepiride Amaryl 1, 2, 3, 4 0.5
Non- Nateglinide Starlix 60, 120 tid with 60 6-8 With meal
sulfonyl meal
urea Repaglinide Novonorm 1, 2, 3, 4 tid with 1 6-8 With meal
meal
 Pharmacological Comparison of Sulfonylureas
Gliben- Glime-
Tolbutamide Gliclazide Glipizide clamide piride

Relative potency 1 30 50 - 100 150 - 400 400-1000

mg/tablet 500 80 5 5 1

Plasma peak (h) 3 4 1 3 2.4

Duration of 6 - 10 10 -20 10 -16 12 -24 24

action (h)

• Gerich N. Engl. J. Med 321 (18) 1231-45,1989

• HMR Amaryl Monograph
 Sulfonilurea

Kontra indikasi
• DM tipe 1
• Kehamilan
• Menyusui

Sulfonilurea- hati-hati pada ggn fs hati dan ginjal

Meglitinides – ggn. Fungsi hati berat

Slides current until 2008

 Sulfonil urea
Ingat !!
Hipoglikemia
Ada yang dapat diberikan satu kali sehari, sehingga lebih
mudah diingat untuk minum obat
Generasi I, spt, chlorpropamide dapat terakumulasi dan
menyebabkan hipoglikemia .
 Alpha glucosidase
inhibitors(Acabose)
Acarbose is a pseudo-
oligosaccharide that
reversibly
inhibits -glucosidases

Glucobay®
-glucosidases are enzymes
in the gut that breakdown
complex carbohydrates –
This reduces and delays the
postprandial rise in blood
glucose levels
Oligosaccharides
from starch
 Acarbose acts non-systemically to delay
carbohydrate absorption

Without With acarbose

Acarbose
Stomach

Upper small
Carbohydrate
intestine
absorption

Carbohydrates

Lower small
Carbohydrate
intestine absorption
Alpha glucosidase inhibitors
Memperlambat pemecahan sukrosa dan starch dengan demikian memperlambat
absorpsi.

Memperlambat kenaikan glukosa post-prandial

Efek samping:

Flatulence, abdominal discomfort , diarrhoea

Sebagai dosis tunggal, tidak menyebabkan hipoglikemia

Hipoglikemia dapat terjadi jika ditambahkan dengan golongan insulin

sekretagogue(e.g. a sulphonylurea)

Slides current until 2008

 Prinsip mekanisme kerja acarbose

Glucose absorption is slower

and stretched over a longer
time period Resorption of glucose in the small intestine

normale
absorption

Less glucose per time unit under acarbose

will reach the blood stream (same integral)

Time

Less insulin is needed

Should protect the ß-cell

Golongan Generik Merk mg/tab Dosis Dosis Lama Frek.
Harian Awal Kerja / hari

 Gluk. Acarbose Glucobay 50 - 100 150 50 - 1-3

- Inhibitor
 4. Thiazolidinedion
Troglitazone

Rosiglitazone

Pioglitazone

Spesifik pada Reseptor PPAR gama

 Thiazolidinediones

Meningkatkan sensitivitas terhadap insulin di otot, jaringan

lemak dan hati.

Mengurangi sekresi glukosa dari hati

Mengubah distribusi lemak melalui penurunan lemak visceral

dan meningkatkan lemak perifer.
efek samping

Peningkatan berat badan, retensi air

ISPA dan sakit kepala

Menurunkan haemoglobin
Slides current until 2008
 Insulin Glucose
transloca
tion
Insulin
receptor

Synthesis GLUT 4

PPAR RXR mRNA

PPRE transcription
promoter Coding reg

Modified from Howard L. Foyt et al. Thiazolidinediones. Diabetes Mellitus: a Fundamental and Clinical Text, 2 nd Ed.
Resistensi Insulin
Insulin
Glucose

receptor X

PPAR +RXR
X Synthesis GLUT 4
mRNA

PPRE transcription
promoter Coding reg

Modified from Howard L. Foyt et al. Thiazolidinediones. Diabetes Mellitus: a Fundamental and Clinical Text, 2 nd Ed.
Pioglitazone reduced Insulin resistance
Insulin Glucose
transloca
tion
Insulin
receptor

PPAR +RXR
Synthesis GLUT 4
mRNA
Pio

PPRE transcription
promoter Coding reg

Modified from Howard L. Foyt et al. Thiazolidinediones. Diabetes Mellitus: a Fundamental and Clinical Text, 2 nd Ed.
 Thiazolidinediones
Kontra indikasi
• Penyakit hati, gagal ginjal dan riwayat penyakit jantung
tidak dikontra indikasikan pada gagal ginjal.
Keuntungan
• Menurunkan kadar kolester olLDL- dan meningkatkan kadar
kolesterol HDL

Slides current until 2008

Hormon Incretin
Efek Incretin : GLP-1 dan GIP
 DPP-4 Inhibition
Prevent DPP-1v destruction by DPP-4 enzym
Increases Levels GLP-1 and GIP

Meal DPP-4 inhibitor

DPP-4
Intestinal enzyme
GIP and GLP-1
release

GIP (1-42)
GIP (1–42) Rapid degradation
GLP-1 (7-36)
GLP-1 (7–36) (minutes)

GIP and GLP-1 actions

Adapted from Deacon CF et al Diabetes 1995;44:1126–1131; Kieffer TJ et al Endocrinology 1995;136:3585–3596; Ahrén B Curr Diab Rep 2003;3:365–372;
48 CF et al J Clin Endocrinol Metab 1995;80:952–957; Weber AE J Med Chem 2004;47:4135–4141.
Deacon
Blocking DPP-4 Can Improve Incretin Activity and Correct the
Insulin:Glucagon Ratio in T2DM
 Insulin
T2DM
Incretin
Further impaired
response Hyperglycemia
islet function
diminished

 Glucagon

DPP-4 inhibitor
 Insulin

Incretin
Improved islet Improved
activity
function glycemic control
prolonged

 Glucagon
DPP-4=dipeptidyl peptidase-4; T2DM=type 2 diabetes mellitus
Adapted from Unger RH. Metabolism. 1974; 23: 581–593. Ahrén B. Curr Enzyme Inhib. 2005; 1: 65–73.
 DPP-4 inhibitor
Sitagliptin (Januvia)

Vildagliptin ( Galvus)

Saxagliptin (Onglyza)
 Clinical implication
Characteristic Sitagliptin Vildagliptin Saxagliptin
MK-0431 LAF237 BMS-477118
Therapeutic dose 100 2x50 5
(mg/day)
Half life Long Short Short (but active
metabolite)
Administration Once daily Twice daily Once daily
Active metabolite No No Yes (BMS-510849)
Fraction bound to Intermediate Low Very low
protein (%)
Renal excretion Predominant Intermediate Predominant
Dose reduction Yes (25-50 mg) No Yes (2.5 mg)
with renal
impairment
 Which the alternative therapy?
HbA1C Advantages Disadvantages
Metformin 1-2 No hypoglycemia,no weigh gain GI symptomps
Broad benefit CI renal insufisiency
SU 1.5 Rapidly effective Weight gain and hypoglycaemia
inexpensive
TZD 0.5–1.4 No hypoglycaemia, some benefits on lipids fluid retention, heart failure, weight
and inflamtion gain, expensive
Insulin 1.5–3+ Most effective, no maximum doze, improved Hypoglycaemia, weight gain, need for
lipid profile SMBG
AGI 0.5–0.8 No hypoglycaemia, weight neutral GI side-effects, expensive

GLP-1 analogue 0.5–1.0 No hypoglycaemia, weight loss GI side-effects, expensive, injected

DPP-4 inhibitor, 0.5–0.8 Weight neutral Long-term safety not established,

expensive
Meglitinide 1.0–1.5 Fewer hypos than sulfonylurea TID dosing, expensive

Pramlintide 0.5–1.0 Weight loss Three injections daily, frequent GI side

effects, long-term safety notestablished,
expensive

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

 Jika OHO TIDAK Efektif
Analisa diet dan olah raga

Pertimbangkan pemberian insulin long-akting pada malam hari

Pertahankan metformin

Pertimbangkan mengurangi atau menghentikan sulfonilurea di

pagi hari
Algoritme Perkeni (2011)

<7%
Factors to Consider when Choosing an Anti
Hyperglycemic agents

• Effectiveness in lowering glucose

• Extraglycemic effects that may reduce long-

term complications

• Safety profile

• Tolerability

• Expense

• Effect on body weight

Nathan DM et al. Diabetes Care 2006;29(8):1963-72.

 Prinsip terapi kombinasi

Dua atau lebih OHO yang mempunyai mekanisme kerja

yang berbeda
Jika pemberian obat kombinasi menghindari dosis maksimal
Efek samping lebih sedikit dibandingkan mono terapi
 Target Pengendalian Diabetes
(Perkeni 2006)
Baik Sedang Buruk

Gula darah puasa ( mg/dl) 80-109 110-125 ≥126

Gula darah 2 jam (mg/dl) 80-144 145-179 ≥180

A1c (%) <6,5 6,5-8 >8

Kolesterol total (mg/dl) <200 200-239 ≥240

Kolesterol LDL ( mg/dl) <100 100-129 ≥130
Kolesterol HDL (mg/dl) >45
Trigliserida( mg/dl) <150 150-199 ≥200
>25
IMT ( kg/m2) 18,5-22,9 23-25

Tekanan darah (mmHg) <130/80 130-140/80-90 >140/90

INSULIN
 Indikasi Terapi Insulin
Temporal :
Permanen :
Kadar gula terlalu tinggi
• gagal jantung yang tidak taha
Hamil
obat minum
Penyakit akut dg GD tinggi • Gagal kombinasi ADO
Penggunaan obat yang meningkatkan • Efek samping obat ADO
GD
• DM tipe 1
Sekitar operasi • Gangguan fungsi hati berat
Gagal ginjal
Selama perawatan di rumah sakit
Serangan jantung atau strok
Humalog, Novorapid, Apidra

Actrapid, Humulin R

Humulin N, Insulatard

Lantus
Levemir
 The Basal-Bolus Insulin Concept

Endogenous Insulin
Bolus Insulin
Insulin Effect

Basal Insulin

B L D HS
Time of Administration
B, breakfast; L, lunch; D, dinner; HS, bedtime.
Adapted from:
1. Leahy JL. In: Leahy JL, Cefalu WT, eds. Insulin Therapy. New York, NY: Marcel Dekker, Inc.; 2002.
2. Bolli GB et al. Diabetologia. 1999;42:1151-1167.
 The BENEFITS AND RISKS OF MEDICATIONS (Endocr Pract. 2009;15)(No.6)
MEDICATIONS*

GLP-3 Sulfonyl
Metformin DPP4 Agonist urea Glinide** Thiazolidinedione Colesevelam Alpha- Insulin Pramlintide
(MET) inhibitor (Increatin (SU) TZD) glucosidase
mimetic) Inhibitor (AGI)

BENEFITS

Postprandial Mild Moderate Moderate to Moderate Moderate Mild Mild Moderate Moderate Moderate to
Glucose (PPG)- marked to marked marked
lowering

Fasting glucose Moderate Mild Mild Moderate Mild Moderate Mild Neutral Moderate Mild
(FPG) –lowering to marked

Nonalcoholic fatty
liver disease Mild Neutral Mild Neutral Neutral Moderate Neutral Neutral Neutral Neutral
(NAFLD)

RISKS

Hypoglycemia Neutral Neutral Neutral Moderate Mild Neutral Neutral Neutral Moderate Neutral
To severe

Gastrointestinal Moderate Neutral Moderate Neutral Neutral Neutral Moderate Moderate Neutral Moderate
symptoms

Risk of use with Severe Moderate Moderate Moderate Neutral Mild Neutral Neutral Moderate Unknown
renal insufficiency

Contraindicated in
liver failure or Severe Neutral Neutral Moderate Moderate Moderate Neutral Neutral Neutral Neutral
predisposition to
lactic acidosis

Heart failure/ Use with Mild/Moderate Neutral

Edema caution in Neutral Neutral Neutral Neutral Contraindicated Neutral Neutral Uniess with Neutral
CHF In class 3,4 CHF TZD

Weight gain Benefit Neutral Benefit Mild Mild Moderate Neutral Neutral Mild to Benefit
Moderate

Fractures Neutral Neutral Neutral Neutral Neutral Moderate Neutral Neutral Neutral Neutral

Drug-Drug Neutral Neutral Neutral Moderate Moderate Neutral Neutral Neutral Neutral Neutral
interaction

Glycemic Control Algorithm,

Type of Insulin Preparation & Action
PENDAHULUAN:

Insulin :
▪ hormon utama yang mengontrol metaolisme
▪ effek : menurunkan kadar gula darah (BG)
▪  insulin ( insulin resistance)  DM

konsekuensi
STRUKTUR KIMIA:

Fig . Insulin molecule

SINTESIS & SEKRESI INSULIN
Sintesis & sekresi
Faktor-faktor yang mempengaruhi sekresi insulin
Fig . 2-phases release of insulin
Efek insuli pada saat puasa dan makan
Mekanisme kerja insulin

Fig. Insulin Signaling Pathway

 Farmakokinetik Insulin

☺ GIT : dirusak sc, iv

☺ paru:  inhalasi insulin
☺ Eliminasi : hati & ginjal
gagal ginjal  dosis diturunkan
☺ masalah : fluktuasi insulin plasma
 fluktuasi gula darah
 Sediaan insulin
Prinsip:
1. Kerja cepat : (lispro dan aspart)
Onset of action dan duration of action sangat cepat
Onset of action : 5-15 menit (lispro); 10-12 menit(aspart)
Puncak : 1 jam
Duration of action : 3-5 jam
menyerupai sekresi insulin endogen secara fisiologis pada saat
makan
Pemberian :SC, CSII
Dapat dicampur dengan NPH, lente, atau ultralente dalam satu
siring tanpa mempengaruhi absorpsi
Diberikan segera sebelum makan (5 menit sebelum makan)
 Sediaan insulin
2. Kerja pendek: (regular insulin)
– Onset of action cepat
– Onset of action : 30 menit (lispro)
– Puncak : 2 dan 3 jam
– Duration of action : 5-8 jam
– Hexamer  mula kerja dan lama kerjanya lebih
lama
– Pemberian : dapat diberikan iv (ketoasidosis,
setelah operasi atau infeksi akut)
– Diberikan 30 menit sebelum makan
 Sediaan insulin
3. Kerja sedang : (lente,NPH)insulin
 Lente insulin:
 Campuran 30% semilente (onset of action cepat) +
70% ultralente insulin (onset and duration of action
panjang)
 NPH
 onset of action lambat
 Terdiri dari kombinasi protamin dan insulin
 Setiap molekul protamin mengandung 6 molekul
insulin
 Setelah pemberian SC, enzim proteolitik jaringan
mendegradasi protamin  insulin dapat diabsorpsi

 Sediaan insulin
4. Kerja panjang:

ultra lente

Glargin insulin
Onset of action: 1-1,5 jam
Duration of action: 11-24 jam atau lebih
Biasanya diberikan 1 kali sehari tapi, kadang-kadang 2 kali sehari.
Tidak dapat dicampur dengan insulin lain dalam satu siring
Pola absorpsi tergantung tempat injeksi
Cara pemberian insulin
Lokasi/tempat
injeksi
Tabel. Beberapa sediaan insuli yang dipakai di AS
Fig.
Fig. Extent
Extent and
and DOA
DOA of
of various
various insulin
insulin
 Glargine

86
Profile of Insulin Glargine vs NPH
NPH
Glargine

87
 Indikasi Insuli n

☺ DM tipe 1
☺ diabetic ketoacidosis, nonketotic coma
☺ DM tipe 2  yang tidak terkontrol hanya dengan diit / OHO
☺ penggunaan jangka pendek : operasi, infeksi, AMI
☺ gestational diabetes
☺ EMG treatment of hyperkalemia
insulin + glucose   extra cellular K+ (redistribution into the cell)
Preparasi insulin

1.
1. Portable
Portable pen
pen injections
injections

2.
2. Continuous
Continuous Subcutaneous
Subcutaneous Insulin
Insulin Infusion
Infusion Devices
Devices
(CSII,
(CSII, INSULIN
INSULIN PUMPS)
PUMPS)

3.
3. Inhaled
Inhaled Insulin
Insulin
 - Replaceable cartridge of 100 U
- Portable, comfortable
- No need of syringe & bottle

1. PORTABLE PEN INJECTORS

 - The most physiologic method of insulin replacement
  Individual basal & bolus insulin  BG self monitoring result

2. CONTINUOUS SUBCUTANEOUS INSULIN INFUSION DEVICES

(CSII, INSULIN PUMPS)
 3. INHALED INSULIN

- Aerosol insulin
- Small particle  alveolar wall  circulation
- Rapid onset & short DOA 
[ to correct High BG / cover meal time
BUT not to provide basal insulin coverage ]
Insulin Degradation
Hydrolysis of the disulfide linkage between A&B chains.
60% liver, 40% kidney(endogenous insulin)
60% kidney,40% liver (exogenous insulin)
Half-Life 5-7min (endogenous insulin)
Delayed-release form( injected one)
Usual places for injection: upper arm, front& side parts of the
thighs& the abdomen.
Not to inject in the same place ( rotate)
Should be stored in refrigerator& warm up to room temp before
use.
Must be used within 30 days.

93
Efek samping

A. Hipoglikemia ….!!!!
• Menunda jadwal makan
• Aktivitas berlebihan dari biasanya
• Kurang asupan karbohidrat

B. Insulin allergy & resistance

- insulin allergy (type-1 hy-sensitivity rx)  very rare
- immune insulin resistance (IgG anti-insulin Ab)

C. Lipodystrophy pada tempat suntikan

- atrophy / hypertrophy subcutaneous fatty tissue
 Methods of Adminisration
Insulin Syringes

Pre-filled insulin pens

External insulin pump

Under Clinical Trials

Oral tablets

Inhaled aerosol

Intranasal, Transdermal

Insulin Jet injectors

Ultrasound pulses

95
96