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ORAL ANTI DIABETIC-Grandcity 2015 PDF
ORAL ANTI DIABETIC-Grandcity 2015 PDF
WESTERN
PACIFIC
INCREASE
46%
In
YEAR 2035
2
POSISI INDONESIA DALAM JUMLAH
PENDERITA DM di DUNIA
3
KOMPLIKASI
KRONIS
DM
ADA-‐EASD
Position
Statement
Update:
Management
of
Hyperglycemia
in
T2DM,
2015
GLYCEMIC
TARGETS
- HbA1c
<
7.0%
(mean PG
∼150-‐160 mg/dl
[8.3-‐8.9 mmol/l])
- Pre-‐prandial
PG
<130 mg/dl
(7.2 mmol/l)
- Post-‐prandial
PG
<180 mg/dl
(10.0 mmol/l)
- Individualization is the key:
Ø Tighter
targets
(6.0
-‐ 6.5%)
-‐ younger,
healthier
Ø Looser
targets
(7.5
-‐ 8.0%+)
-‐ older,
comorbidities,
hypoglycemia
prone,
etc.
- Avoidance
of
hypoglycemia
Deaths related
21% to diabetes
HbA1c
Microvascular
37% complications
1%
Myocardial
14% infarction
ACCORD ê çè é
ADVANCE ê çè çè
VADT ê çè çè
Kendall DM, Bergenstal RM. © International Diabetes Center 2009
Initial
Trial
UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:854.
Holman RR et al. N Engl J Med. 2008;359:1577. DCCT Research Group. N Engl J Med 1993;329;977.
Nathan DM et al. N Engl J Med. 2005;353:2643. Gerstein HC et al. N Engl J Med. 2008;358:2545. Long
Term
Follow-‐up
Patel A et al. N Engl J Med 2008;358:2560. DuckworthW et al. N Engl J Med 2009;360:129. (erratum:
Moritz T. N Engl J Med 2009;361:1024)
ADA-‐EASD
Position
Statement
Update:
Management
of
Hyperglycemia
in
T2DM,
2015
BACKGROUND
• Overview
of
the
pathogenesis
of
T2DM
- Insulin
secretory dysfunction
- Insulin
resistance
(muscle,
fat,
liver)
- Increased
endogenous
glucose
production
- Decreased
incretin effect
- Deranged
adipocyte
biology
+ peripheral
hepatic renal glucose
glucose glucose uptake
production excretion
Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011
Multiple,
Complex
Pathophysiological
Abnormalities
in
T2DM
GLP-1R Insulin
agonists pancreatic
Glinides S U s insulin
incretin
effect secretion
DPP-4 Amylin pancreatic
inhibitors mimetics glucagon
_ secretion DA
gutA G I s
carbohydrate
agonists
?
delivery & HYPERGLYCEMIA
absorption
Metformin T Z D s
_
Bile acid
sequestrants
+ peripheral
hepatic renal glucose
glucose glucose uptake
production excretion
Adapted from: Inzucchi SE, Sherwin RS in: Cecil Medicine 2011
Natural
Progression
of
Type
2
Diabetes
May
Result
in
the
Need
for
Combination
Therapy
– Maintaining
glycemic control
in
patients
with
type
2
diabetes
can
be
challenging
due
to
the
natural
progression
of
the
disease1
– The
natural
progression
of
type
2
diabetes
may
require
multiple
agents
with
comprehensive
mechanisms
of
actions1
– An
agent
of
one
therapeutic
category
may
be
added
to
an
agent
of
a
different
therapeutic
category,
with
the
following
exception2:
– Agents
with
similar
mechanisms
of
action
may
not
be
effective
in
combination
9
HbA1c (%)
If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference choice dependent on a variety of patient- & disease-specific factors):
Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Triple Sulfonylurea Thiazolidine-
dione
DPP-4
Inhibitor
SGLT-2
Inhibitor
GLP-1 receptor
agonist
Insulin (basal)
therapy + + + + + +
TZD SU SU SU SU TZD
If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGLT2-i:
Metformin
+
Combination
Figure
2.
Anti-‐hyperglycemic
therapy
injectable
Insulin +
Basal Mealtime Insulin or GLP-1-RA
in
T2DM:
therapy General
recommendations
‡!
Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
Healthy eating, weight control, increased physical activity & diabetes education
Mono-
therapy Metformin
Efficacy* high
Hypo risk low risk
Weight neutral/loss
Side effects GI / lactic acidosis
Costs low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference choice dependent on a variety of patient- & disease-specific factors):
Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Dual Sulfonylurea Thiazolidine- DPP-4 SGLT2 GLP-1 receptor Insulin (basal)
therapy†! dione inhibitor inhibitor agonist
Efficacy* high high intermediate intermediate high highest
Hypo risk moderate risk low risk low risk low risk low risk high risk
Weight gain gain neutral loss loss gain
Side effects hypoglycemia edema, HF, fxs rare GU, dehydration GI hypoglycemia
Costs low low high high high variable
If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference choice dependent on a variety of patient- & disease-specific factors):
Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Triple Sulfonylurea Thiazolidine-
dione
DPP-4
Inhibitor
SGLT-2
Inhibitor
GLP-1 receptor
agonist
Insulin (basal)
therapy + + + + + +
TZD SU SU SU SU TZD
If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGLT2-i:
Metformin
+
Combination
Figure
2.
Anti-‐hyperglycemic
therapy
injectable
Insulin +
Basal Mealtime Insulin or GLP-1-RA
in
T2DM:
therapy General
recommendations
‡!
Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
Healthy eating, weight control, increased physical activity & diabetes education
Mono-
therapy Metformin
Efficacy* high
Hypo risk low risk
Weight neutral/loss
Side effects GI / lactic acidosis
Costs low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference choice dependent on a variety of patient- & disease-specific factors):
Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Dual Sulfonylurea Thiazolidine- DPP-4 SGLT2 GLP-1 receptor Insulin (basal)
therapy†! dione inhibitor inhibitor agonist
Efficacy* high high intermediate intermediate high highest
Hypo risk moderate risk low risk low risk low risk low risk high risk
Weight gain gain neutral loss loss gain
Side effects hypoglycemia edema, HF, fxs rare GU, dehydration GI hypoglycemia
Costs low low high high high variable
If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference choice dependent on a variety of patient- & disease-specific factors):
Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Triple Sulfonylurea Thiazolidine-
dione
DPP-4
Inhibitor
SGLT-2
Inhibitor
GLP-1 receptor
agonist
Insulin (basal)
therapy + + + + + +
TZD SU SU SU SU TZD
If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGLT2-i:
Metformin
+
Combination
Figure
2.
Anti-‐hyperglycemic
therapy
injectable
Insulin +
Basal Mealtime Insulin or GLP-1-RA
in
T2DM:
therapy General
recommendations
‡!
Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442
Healthy eating, weight control, increased physical activity & diabetes education
Mono-
therapy Metformin
Efficacy* high
Hypo risk low risk
Weight neutral/loss
Side effects GI / lactic acidosis
Costs low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference choice dependent on a variety of patient- & disease-specific factors):
Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Dual Sulfonylurea Thiazolidine- DPP-4 SGLT2 GLP-1 receptor Insulin (basal)
therapy†! dione inhibitor inhibitor agonist
Efficacy* high high intermediate intermediate high highest
Hypo risk moderate risk low risk low risk low risk low risk high risk
Weight gain gain neutral loss loss gain
Side effects hypoglycemia edema, HF, fxs rare GU, dehydration GI hypoglycemia
Costs low low high high high variable
If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference choice dependent on a variety of patient- & disease-specific factors):
Metformin Metformin Metformin Metformin Metformin Metformin
+ + + + + +
Triple Sulfonylurea Thiazolidine-
dione
DPP-4
Inhibitor
SGLT-2
Inhibitor
GLP-1 receptor
agonist
Insulin (basal)
therapy + + + + + +
TZD SU SU SU SU TZD
If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGLT2-i:
Metformin
+
Combination
injectable Basal Insulin + Mealtime Insulin or GLP-1-RA
therapy‡! Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-442