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A1C 7%
36%
BP < 130/80
48 %
7,3%
12%
Percentage of Risk
Lower
Risk of
Diabetesrelated
Endpoints*
16%
Lower
21%
Lower
Risk of
Myocardial
Infarction
Risk of
Retinopathy
at 12 Years*
24%
Lower
25%
Lower
Risk of
Risk of
Cataract
Extraction* Microvascular
Endpoints*
-50
*Decreases were statistically significant.
From UKPDS 33. Lancet. 1998;352:837-853.
STUDI UKPDS.
EVERY 1% reduction in HbA1C
1%
REDUCED RISK*
Heart attacks
- 14%
- 21%
Microvascular complications
- 37%
Lifestyle
+
Metformin
Lifestyle +
Metformin+
Insulin basal
Lifestyle +
Metformin+
Insulin Intensive
Lifestyle +
Metformin+
Sulfonylurea
Lifestyle +
Metformin+
Pioglitazone
Lifestyle +
Metformin+
Pioglitazone+
Sulfonylurea
Lifestyle +
Metformin+
GLP-1 Agonis
Lifestyle +
Metformin+
Insulin Basal
Glipizide.
Gliguidone
Glimepiride
3. Thiazolidinedions (Meningkatkan
masukan glukosa otot)
Pioglitazone.
Rosiglitazone.
4. lfa-Glucosidase Inhibitor
(Menghambat absorpsi karbohidrat)
Acarbose.
Miglitol.
Obat hipoglikemia.
Meningkatan sekresi insulin melalui :
Penutupan K-ATP chanel yang
Sulfonilurea
Kalsium
Glukosa
K+ Channel
GLUT2
SUR
1
Calcium
Channel
Depolarisasi
K+
Kalsium influx
ATP
Glucose6-phasphate
Sekresi insulin
Eksositosis
granule insulin
Sitoplasma
Sel
Metabolisme
6 December 2016
15
First generation :
acetohexamide, chlorpropamide,
tolbutamide, tolazamide.
second generation:
glibenclamide (12 24 jam)(glyburide),
Kontraindikasi :
disfungsi liver, gagal ginjal, gagal
Metformin
Reduces hepatic gluconeogenesis
Decrease A1C by 1-2% (level 1A)
Less weight gain and less hypo-glycemia vs.
Thiazolidinediones :
meningkatkan sensitifitas insulin karena
Thiazolidinediones
Pioglitazone and Rosiglitazone
True insulin sensitizers
Decreases A1C ~ 0.9 to 1.5% (level 1A)
plus metformin reduces A1C ~1.0 to
Acarbose
Decrease A1C: 0.7 to 1.8% (level 1A)
In combination 0.2 to 1.4%,
Hormon Increatin
Incretin Mimetics:
GLP-1 analogue :
Exenatide .
Liraglutide.
DPP-4 Inhibitor :
Sitagliptine ,
Vildagliptine .
Saxagliptin.
Linagliptin.
pancreas dan
menghambat sekresi glukagon.
Efek lainya :
Menghambat pengosongan gaster.
Memperpanjang absorsi glukosa.
Menurunkan nafsu makan.
life 4 jam).
Liraglutide (injeksi satu kali/hari dengan
half-life 11-13 jam).
GLP-1 agonist :
Dapat ditoleransi dengan baik dengan efek
Amylin analog
Pramlintide acetate :
Memperlambat pengosongan
lambung,
Menurunkan pelepasan glukogon
prosprandial,
Modulasi appetite.
Dual PPAR Dual Agonists:
Glitazars
CB1 Endocannabinoid Receptor (Appetite)
Antagonist:
Rimonabant.
ADIPOSE
TISSUE
LIVER
GLUCOSE
PRODUCTION
Biguanides
MUSCLE
PERIPHERAL
GLUCOSE UPTAKE
Thiazolidinediones
Thiazolidinediones
Hyperglycemia
Biguanides
PANCREAS
INTESTINE
Alpha-glucosidase inhibitors
GLUCOSE ABSORPTION
INSULIN Secretion
Sulfonylureas
Meglitinides
Thiazolidinediones
Increase glucose
uptake in skeletal
muscle and decrease
lipolysis in adipose
tissue
Biguanide (metformin)
Decreases hepatic
glucose production and
increases uptake
-Glucosidase inhibitors
Delay intestinal
carbohydrate absorption
1.
2.
3.
4.
Monoterapi.
Kombinasi Terapi.
Intensif Kombinasi Terapi.
Intensif Insulin Terapi
Option:
Metformin.
Thiazolidinediones.
Dipeptidyl-peptidase 4 inhibitor (DD4-I).
- Glucosidase inhibitor.
Secretagogue + Metformin
Secretagogue + Thiazolidinediones.
Secretagogue + - Glucosidase
inhibitor.
Thiazolidinediones + Metformin.
Dipeptidyl-peptidase 4 inhibitor (DD4-I)
+Metformin.
Dipeptidyl-peptidase 4 inhibitor (DD4-I)
+ Thiazolidinediones.
Secretagogue +Metformin +
Thiazolidinediones
Pioglitazone + Metformin.
Rosiglitazone + Metformin.
Rosiglitazone + Glimepiride
Pioglitazone + Glimepiride
Rapid-acting insulin analog or Premix
insulin analogs.
Oral agent + long-acting insulin analog.
Semua oral agent bisa dikombinasi
dengan insulin.
Rodbard et al, Endocrine Practice, 2007)
Ketika
A1c > 10 %.
Insulin ( Brand)
Onset
Peak
Effectiv
e
Duratio
n
5-15 min
30-90 min
<5h
5-15 min
30-90 min
<5 h
5-15 min
30-90 min
<5 h
5-15 min
30-90 min
5-8 h
30-60 min
2-3 h
5-8 h
2-4 h
4-10 h
10-16 h
Rapid-Acting
Short-acting
Regular
Intermediate,basal
NPH
Insulin ( Brand)
Onset
Peak
Effective
Duration
2-4 h
Np Peak
20-24 h
3-8 h
No peak
5,7-23,2 h
Long-Acting, basal
Premixed
75% Insulin lispro protamine suspension/
25 % Insulin lispro injection
(Humalog Mix 75/25)
5-15 min
Dual
10-16 h
5-15 min
Dual
10-16 h
5-15
min
Dual
10-16 h
30-60
min
Dual
10-16 h
Type of Insulin
& Brand
Names
Onset
Peak
Duration
Pre-Mixed*
Humulin 70/30
30 min.
2-4
hours
14-24
hours
Novolin 70/30
30 min.
2-12
hours
Up to 24
hours
Novolog 70/30
10-20
min.
1-4
hours
Up to 24
hours
Humulin 50/50
30 min.
2-5
hours
18-24
hours
Humalog mix
75/25
15 min.
30
min.2
hours
16-20
hours
56
Exenatide + secretagogue
(sulfonylurea)
Exenatide + Metformin.
Exenatide + secretagogue + Metformin
Exenatide + Thiazolidinediones
Pramlintide + prandial insulin.
Basal bolus insulin pada pasien A1c >
8,5%
Rodbard et al, Endocrine Practice, 2007)
bloker, diuretik.
Singel atau kombinasi.
Manfaat terapi :
Proteksi terhadap ginjal.
Stabilisasi endothelium.
Menurunkan risiko penyakit ateri koroner.
LDL-kolesterol
Goal terapi < 100 mg/dL.
Apo-B
Goal terapi < 90 mg/dL
Non-HDL-kolesterol.
Goal terapi <130 mg/dL.
HDL-kolesterol
Goal terapi > 50 mg/dL.
Trigleserid.
Goal terapi < 150 mg/dL.
Reomendasi :
Modifikasi pola hidup.
Statin ,fibrat, niacin,ezetimide.
HDL-C :
> 40 mg/dL (laki-laki)
> 50 mg/dL (wanita)
Manfaat terapi:
Menurunkan morbiditas dan mortalitas penyakit
atherosklerosis.