TUJUAN Tx DM

Reduksi hiperglikemia kadar

gula (glukose) darah normal
Menurunkan atau menghilangkan
komplikasi kronik
Memperbaiki kualitas dan
kuantitas hidup

TERAPI NON-FARMAKOLOGIK
PENGATURAN POLA MAKAN
AKTIVITAS
PENGATURAN POLA HIDUP STRESS
ATAU DEPRESI

TERAPI
FARMAKOLOGI

TERAPI FARMAKOLOGIK

INSULIN
OAD

Oral Hypoglycemics
Insulin secretagogues:
Sulfonylureas (oldest)
Meglitinides

Insuline sensitizers:
Biguanide
Thiazolidinediones

Alpha-glucosidase inhibitors
Acrabose
Miglitol

Primary sites of action of oral

antidiabetic agents
-glucosidase
inhibitors

Sulfonylureas/
meglitinides

Carbohydrate
breakdown/
absorption

Insulin
secretion

Biguanides

Thiazolidinediones

Glucose
output
Insulin resistance

Insulin
resistance

Kobayashi M. Diabetes Obes Metab 1999; 1 (Suppl. 1):S32S40.

Nattrass M & Bailey CJ. Baillieres Best Pract Res Clin Endocrinol Metab 1999;

Indications for Oral

Hypoglycemics
They are used to lower blood sugar
levels in patients that diet and
exercise have failed.
The patient must have some
pancreatic function left.
They can be used as a monotherapy
or in conjunction with other oral
hypoglycemics.

Sulfonylureas (Oral Hypoglycemic drugs)

First generation

Second generation

Short

Intermediate

Long

Short

Long

acting

acting

acting

acting

acting

Tolbutamide

Acetohexamide
Tolazamide

Chlorpropamide

Glipizide

Glyburide
(Glibenclamide)
Glimepiride

Sulfonylureas
Stimulate insulin secretion from the beta
cells of the pancreas, thus increasing
insulin levels
Beta cell function must be present
Result: lower blood glucose levels
First-generation drugs not used as
frequently now

FIRST GENERATION SULPHONYLUREA COMPOUNDS

Tolbutamid
shortacting

Acetohexamid
e
intermediateacting

Tolazamide
intermedia
te-acting

Absorptio
n

Well

Well

Slow

Well

Metabolis
m

Yes

Yes

Yes

Yes

Metabolit
es

Inactive*

Active +++ **

Active ++
**

Inactive **

Half-life

4 - 5 hrs

6 8 hrs

7 hrs

24 40 hrs

Duration
of action

Short
(6 8 hrs)

Intermediate
(12 20 hrs)

Intermedia
te
(12 18
hrs)

Long
( 20 60 hrs)

Urine

Urine

Excretion
Urine
* Good forUrine
patients with renal
impairment

** Patiens with renal impairment can expect long t 1/2

Chlorpropamid
e
long- acting

SECOND GENERATION SULPHONYLUREA

COMPOUNDS
Glipizide
Shortacting
Absorption
Metabolis
m
Metabolite
s
Half-life

Well
Yes

Glibenclamid Glimepirid
e
e
(Glyburide)
Longacting
Long-acting
Well
Well
Yes
Yes

Inactive

Inactive

Inactive

3 4 hrs

Less than 3
hrs
12 24 hrs

5 - 9 hrs

Duration of 10 16
action
hrs

12 24 hrs

Meglitinides
Meglitinides
repaglinide
nateglinide

Meglitinides
Action similar to sulfonylureas
Increase insulin secretion from the
pancreas

Biguanides
Biguanides
metformin
Mechanism action
Increase peripheral glucose utilization
Inhibits gluconeogenesis
Impaired absorption of glucose from the
gut
Decrease blool glucagon
Does not increase insulin secretion from the
pancreas (does not cause hypoglycemia)

Thiazolidinediones
Thiazolidinediones
pioglitazone
rosiglitazone
Also known as glitazones
Mechanism action:

Decrease insulin resistance

Insulin sensitizing drugs
Increase glucose uptake and use in
skeletal muscle
Inhibit glucose and triglyceride production
in the liver

Alpha-glucosidase Inhibitors
Alpha-glucosidase inhibitors
acarbose
miglitol
Mechanism action:
Reversibly inhibit the enzyme alphaglucosidase in the small intestine
Result: delayed absorption of glucose
Must be taken with meals to prevent
excessive postprandial blood glucose
elevations (with the first bite of a meal)

GLP-1R agonists or GLP-1

analogues
GLP-1 receptor agonists
Exendin-4
Exenatide

GLP-1 analogues
Liraglutide a long-acting
glucagon-like peptide-1 (GLP-1

DPP-4 inhibitors
Sitaglipin
Their mechanism of action is thought
to result from increased Incretin
levels (GLP-1 and GIP),which inhibit
glucagon release, increases insulin
secretion and decreases gastric
emptying.

Insulin

Fisiologic Insulin Response to

Constant Glucose stimulus
Level of insulin
secretion

Stimulation by
glucose
First(acut
e) Phase
on
release
Secon
d
Phase
Insulin basal

Baseline

Time

Diabetes Care 1984;7:491-502

Insulins
Mechanism of Action
Substitute for & same effects as
endogenous insulin
Restores the diabetic patients ability to:
Metabolize carbohydrates, fats, and proteins
Store glucose in the liver
Convert glycogen to fat stores
Most now human-derived, using recombinant
DNA technologies
Goal: tight glucose control , to reduce the

incidence of long-term complications

Human-Based Insulins
Rapid-Acting
Most rapid onset of action
Shorter duration
Insulin

Onset
(mins)

Peak (hrs)

Duration
(hrs)

aspart (Novolog)

2-33

1-3

3-5

lispro (Humalog)

2-33

30mins 2.5

3-6.5

glulisine (Apidra)

2-33

30mins 1.5

1.-25

May be given SC or via continuous SC

infusion
pump (but not IV)

Human-Based Insulins
Short-Acting
regular insulin (Humulin R, Novolin R)
Insulin

Onset (mins)

Peak
(hrs)

Duration
(hrs)

Humulin R

30 mins to 4 hrs

2.5-5

5-10

Novolin R

30

2.5-5

Onset 30 60 minutes
The only insulin product that can be given by IV
bolus, IV infusion, or even IM

Sliding-Scale Insulin Dosing

SC rapid or short-acting doses adjusted
according to blood glucose test results
Typically used in hospitalized diabetic
patients
Or in patients on TPN / enteral tube feedings or
receiving steroids

Subcutaneous insulin is ordered in an amount

that increases as the blood glucose
increases

Human-Based Insulins IntermediateActing

Insulin

Onset
(hrs)

Peak (hrs)

Duration
(hrs)

Humulin N

1-4

4-12

16-28

Novolin N

1-5

4-12

24

Humulin 50/50

0.5

4-8

24

Humulin 70/30

0.5

4-12

24

Novolin70/30

0.5

2-12

24

Isophane (NPH):

Isophane &
Insulin:

Human-Based Insulins
Intermediate-Acting
Insulin

Onset
(hrs)

Peak (hrs)

Duration
(hrs)

lispro protamine &

lispro:
Humalog Mix 75/25

0.25-0.5

0.5-1.5

12-24

Novolog Mix 70/30

0.2-0.33

2.4

24

Lente Iletin II

1-1.5

8-12

24

Novolin L

1-4

7-15

20-28

Insulin Zinc
Suspension:

Human-Based Insulins
Long-Acting
Insulin

Onse
t

Peak

Duration

glargine (Lantus

No peak activity

24 (when
administered at hs)

detemir (Levemir)

6-8

6-28

Profile of Insulin Glargine vs

NPH
NPH
Glargine

DM tipe 2

ADOLESCENT

PEDIATRI

NON - OBESE

add
add

Sulfonilurea

Glinid

Metformin

Glitazon

Insulin

INTOLERANSI KARBOHIDRAT
PADA
TRIMESTER II DAN III

PREGNANCY

DM GESTASIONAL

Tx. DIET

Insulin NPH

Insulin NPH + Reguler

2
:
1

Glyburide
Metformin
KI : Sulfonilurea

DM GESTASIONAL