with OADs
Sugiarto
Divisi Endocrinology, Metabolic and Diabetes of Internal
Medicine FK / Moewardi Hospital Sebelas Maret University
Surakarta
akibat :
Defek sekresi insulin dan glukogon
Defek aktifitas insulin atau resistensi insulin
atau lainnya.
Management diabetes
Klas Diabetes.
Komplikasi Diabetes
Mereview terapi diabetes sebelumnya
Rencana perawatan dan penatalaksanaan
Pemeriksaan Laboratorium
Slide 5
Brain
Intestines Pancreas
pancreatic
incretin insulin
effect secretion
pancreatic
glucagon
secretion ? Kidney
gut
carbohydrate Glucose
delivery and reabsorpsion
absorption
Hyperglycemia
Muscle
Liver
peripheral
glucose
uptake
hepatic
glucose Adipose
production
Adapted from:Inzucchi SE, Sherwin RS. Diabetes Mellitus. In: Goldman L, Ausiello D, eds. Cecil Textbook of Medicine. 23rd Edn. Philadelphia, Pa:
Saunders Elsevier; 2007.
STUDI UKPDS.
*p<0.0001
UKPDS 35, BMJ 2000; 321: 405-12
The benefits of good blood glucose control are
clear
Myocardial
Good control is infarction
≤ 7.0% HbA1c
-14%
HbA1c measures
the average
blood glucose Microvascular
level over the HbA1c complications
last three -1% -37%
months
Deaths related
to diabetes
-21%
Slide 7
Source: UKPDS = United Kingdom Prospective Diabetes Study. Stratton IM
et al. BMJ. 2000;321(7258):405-412.
Relationship of HbA1C to Risk of Microvascular
Complications
Diabetes Control and Complications Trial
(DCCT)
15
13 Retinopathy
Relative Risk (%)
Nephropathy
11
Neuropathy
9 Microalbuminuria
7
5
3
1
6 7 8 9 10 11 12
HbA1C (%)
• Tiazolidindion
• Penghambat • Penghambat SGLT-2
• Penghambat SGLT-2
Glukosidase Alfa • Insulin Basal
• Metformin
• Sulfonylureas (SUs) and glinides
• α-glucosidase inhibitors (AGIs)
• Glucagon-like peptide-1 (GLP-1) agonists
• Thiazolidinediones (TZDs)
• Dipeptidyl peptidase-4 inhibitors (DPP-4
inhibitors)
Slide 13
Metformin
Mode of Action
The primary effects of metformin are to decrease hepatic glucose production and
increase insulin-mediated peripheral glucose uptake
Metformin
Clinical Overview and Contraindications
Metformin
Safety, Tolerability
Efficacy* Contraindications Advantages
and Adherence
Metformin
Little benefit – if any - to go above 2.000 mg
500mg 1000mg 1500mg 2000mg 2500mg 500mg 1000mg 1500mg 2000mg 2500mg
0 0 .0
10
Change vs. Placebo (mg/dl)
30
3 1 .0
40 1 .0 0 .9
4 0 .9
50 1 .2
60 1 .5
6 1 .9 1 .6
70 1 .7
80 7 7 .9 2 .0
2 .0
Pancreatic β-cell
• Sulfonylureas (SUs) and
glinides increase endogenous ATP-sensitive
insulin secretion by binding to Glucose potassium channel
Glycolysis ATP
pancreatic β-cells and triggering uptake
respiration SUs /
a cascade of intracellular
glinides
events1–3
Glucokinase
• The mode of action of SUs and
glinides is similar, but
stimulation of insulin secretion
n o
Depolarizati
is more rapid and short-acting
with glinides
• SU receptors are also found on
other cells, including the
cardiac myocytes
1. Gallwitz B, Haring H-U. Diabetes Obes Metab 2010;12:1–11. 2. Schuit FC, et al. Diabetes 2001;50:1–11. 3. Krentz
AJ, Bailey CJ. Drugs 2005;65:385–411.
Pancreatic Mechanism Sulfonylurea
Sulfonilurea
Kalsium
Glukosa
K+ Channel
Calcium
GLUT2 SUR Channel
1 Depolarisasi Sekresi insulin
K+
Kalsium influx
ATP
Eksositosis
granule insulin
Sitoplasma
Glucose- Metabolisme Sel β
6-phasphate
PLEASE INSERT Presentation title 9 December 2021 18
Slide 19
Sulphonylurea Glinides
Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. Nathan DM, et al. Diabetologia. 2009;52:17–30. Rosenstock J, et al. Diabetes
Care. 2004;27:1265–70.
Slide 20
1. Gallwitz B, Haring H-U. Diabetes Obes Metab 2010;12:1–11. 2. Schuit FC, et al. Diabetes 2001;50:1–11. 3. Krentz
AJ, Bailey CJ. Drugs 2005;65:385–411.
Slide 21
Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. Nathan DM, et al. Diabetologia. 2009;52:17–30. Rosenstock J, et al. Diabetes
Care. 2004;27:1265–70.
Slide 22
Thiazolidinediones (TZDs)
Mode of Action
TZD: Thiazolidinediones
Thiazolidinediones
Clinical Overview
Thiazolidinediones
Safety, Tolerability
Efficacy* Contraindications Advantages
and Adherence
Krentz AJ, Bailey CJ. Drugs 2005;65:385–411. Drug Class Review: Thiazolidinediones. Available at:
http://pharmacy.oregonstate.edu/drug_policy/pages/dur_board/reviews/articles/TZD_ClassReview.pdf . Rizzo M, et al. Expert Opin
Pharmacother. 2008;9:2295–303.
Slide 24
DPP-4 inhibitors
Mode of Action
GI tract Incretins
(GLP-1, GIP) Increases and prolongs
α-cells
GLP-1 effect on α-cells
Intestine
* GIP does not inhibit glucagon secretion by α-cells
DPP-4: dipetidyl peptidase-4; GI: gastrointestinal; GIP:glucose-dependent insulinotropic polypeptide; GLP-1: glucagon-like peptide
Drucker DJ et al. Nature 2006;368:1696–705. Idris I, et al. Diabetes Obes Metab 2007;9:153–65. Barnett A. Int J Clin Pract
2006;60:1454–70. Gallwitz B, et al. Diabetes Obes Metab 2010;12:1–11.
Slide 25
DPP-4 inhibitors
Clinical Overview
DPP-4 inhibitors
Safety, Tolerability and
Efficacy*
Adherence
• HbA1c reduction of 0.5-1% • Generally well tolerated
• FPG reduction of 20 mg/dl • Low risk of hypoglycemia
• PPG reduction of 45-55 mg/dl • Not associated with weight
gain
• Upper respiratory tract
infection5 has been reported in
clinical studies
• Most require only once daily
administration
Ahrèn B. Expert Opin Emerg Drugs 2008;13:593–607. Gallwitz B, et al. Diabetes Obes Metab 2010;12:1–11. Amori RE, et
al. JAMA 2007;298:194–206. Saxagliptin, FDA’s Endocrinologic and Metabolic Drugs Advisory Committee Briefing Document
for April 2009 Meeting: NDA 22-350. Available at: http://www.fda.gov/OHRMS/DOCKETS/ac/09/briefing/2009-4422b1-02-
Bristol.pdf. (accessed Nov 2010). Aschner P, et al. Diabetes Care 2006;29:2632–7.
Effect of GIP and GLP-1 in human body
GLP 1 Agonist
Mode of Action
Pancreas
Net effect:
GLP-1 agonist blood glucose
• Glucagon secretion
α-cell
• β-cell apoptosis
GLP 1 Agonist
Clinical Overview
GLP-1 Agonist
Safety, Tolerability and
Efficacy*
Adherence
• HbA1c reduction of 1-2% • Associated with moderate and
• FPG reduction of 6-12 mg/dl transient nausea, vomiting and
• PPG reduction of 6-18 mg/dl diarrhoea
• Low risk of hypoglycemia and
no evidence of increased CV
risk
• Associated with weight
reduction
• Associated with reduction in
BP
Garber AJ. Diabetes Care 2011;34 (Suppl 2):S279–84. Moretto TJ, et al. Clin Ther 2008;30:1448–60. Drucker DJ. Cell Metab
2006;3:153–65. Amori RE, et al. JAMA 2007;298:194–206.
Slide 29
• Always start with the lowest dose Remember the possibility of
of any blood glucose-lowering
• Forgetfulness
medicine and increase gradually
• Poor motivation
• Using shorter-acting medicines
that reduces the risk of • Depression
hypoglycaemia
• Cognitive deficits
• Hypoglycaemia may increase the • Poly-pharmacy
risk of falls and heart attack in
older people • Reduced manual dexterity
•These factors impact on the ability to
maintain self-care and achieve
maximum benefits from blood glucose-
lowering medicines.
Slide 31
Meglitinides
Increase insulin secretion from Biguanide (metformin)
pancreatic -cells Decreases hepatic glucose
production and increases
uptake
Sulfonylureas
Increase insulin secretion
from pancreatic -cells
-Glucosidase inhibitors
Delay intestinal carbohydrate
absorption
GLP = glucagon-like peptide.
Adapted from Cheng and Fantus. CMAJ. 2005;172:213–226.
Slide 32
in the
cl uded
In
d er
Bin
Inzucci SE, et al. Diabetologia. 2012
Slide 35