PHARMACOTHERAPY

of
DIABETES MELLITUS

dr. Ave Olivia Rahman, MSc.

Bagian Farmakologi FKIK UNJA

DIABETES MELLITUS (DM)

TYPE 1

Insulin-dependent
Diabetes Mellitus
Destruction of
insulin-producing B
cells in the pancreas.

TYPE 2

Non-insulindependent diabetes
Relative insulin
deficiency, Insulin
resistance.

GOAL OF THERAPY
BLOOD SUGAR CONTROL AT NORMAL
OR NEAR-NORMAL VALUE DIET,
EXERCISE, DRUG

TREAT ASSOCIAETED CONDITIONS &

COMPLICATION RISK CONTROL

PHARMACOTHERAPY OF
DM TYPE 1

INSULIN
REPLACEMENT

INSULIN ACTION
In healthy subjects, the amount of insulin is
automatically matched to blood glucose
concentration.

Continue...Insulin Action

Stimulates glikogenesis
Inhibits gluconeogenesis.
Inhibits lipolysis
Stimulates fatty acid synthesis

Insulin Replacement
Subcutaneous
administration
Absorption is
usually most rapid
from the abdominal
wall, followed by
the arm, buttock,
and thigh
Different type of
insulin according to
their duration of
action

Type of Insulin...based on its acting

Type

Onset

Peak

Duration

Ultra rapidacting

15-30
minutes

30 minute2 hours

Shortacting/Regular

30 minutes-1
hours

2-4 hours

6-8 hours

Intermediateacting

2-4 hours

1-8 hours

14-15
hours

Long-acting

1-3 hours

Witout peak 24 hours

Continue...
Ultra rapid-acting

Insulin
Basal

Insulin
Postprandial

Factors Affecting Insulin Absorption

Site of injection
Type of insulin
Subcutaneous blood flow
Smoking
Regional muscular activity at the side of
injection
Volume& concentration of injected insulin
Depth of injection.

Indication of Insulin Therapy

DM type 1
DM type 2 uncontrolled with diet,
excersice, oral antidiabetic drugs
Gestational DM
DM with severe kidney and liver disease
DM with infection, major operation,
malnutrition, tumor, corticosteroid
therapy, graves disease
DM Ketoacidosis

Insulin Dosing
Insulin replacement therapy includes
long acting insulin (basal) and short
acting insulin to provide postprandial
needs.
IHT (Insulin Harian Total) = 0,5 U x
BB (kg)
IPT (Insulin Prandial Total) = 60% dari
IHT dibagi 3 dosis (sarapan, makan
siang, makan malam)
IBT (Insulin Basal Total) = 40% dari IHT

ORAL HYPOGLICEMIC
AGENTS
BIGUANIDE
INSULIN SECRETAGOGUES:
SULFONYLUREAS
NON SULFONYLUREAS (MEGLITINIDE): REPAGLINIDE,
NATEGLINIDE

THIAZOLIDINEDIONES
GLP-1 AGONIST : EXENATIDE
DIPEPTIDYL PEPTIDASE 4 INHIBITORS :
SAXAGLIPTIN, SITAGLIPTIN, VIDAGLIPTIN
ALPHA GLUCOSIDASE INHIBITORS
PRAMLINTIDE

BIGUANIDES

Metformin. 1st line therapy in DM type 2.

Metformin is antihyperglycemic by
decreasing hepatic glucose production
(gluconeogenesis) and by increasing
insulin action in muscle and fat.
Only Metformin has been demonstrated
to reduce macrovascular events in type 2
DM (U.K. Prospective Diabetes Study
Group, 1998b).

Continue...Metformin
CONTRAINDICATION : renal
impairement, hepatic disease, history of
lactic acidosis, cardiac failure, cronic
hypoxic lung disease.
SIDE EFFECTS: lactic acidosis, diarrhea,
abdominal discomfort, nausea, metallic
taste, anorexia.
Metformin can be administered in
combination with sulfonylureas,
thiazolizinediones, and/or insulin.
Available Fixed-dose combinations.

Dosing of Metformin
Available generic Tablet 500 mg,
forte 850 mg.
Dose : 2-3 x 500 mg daily with
meals, max 2,5 g/daily.

SULFONYLUREAS
GROUP 1

SULFONYLUREAS : Stimulating insulin

release from pancreatic cells
SULFONYLUR
EAS

INCREASED INSULIN
SECRETION

SIDE EFFECT : mild- severa hipoglycemia,

(glibenclamide cause up to 20-30%), nausea,
vomiting, cholestatic jaundice,
agranulocytosis, aplastic and hemolytic
anemias, hypersensitivity reactions,
hyponatremia.
DRUG INTERACTION : other sulfonamides,
clofibrate, and salicylates, ethanol.
CONTRAINDICATIONS : type 1 DM, pregnancy,
lactation, significant hepatic or renal
insufficiency for the older preparations

Repaglinide
Stimulates insulin release by closing
ATP-dependent potassium channels
in pancreatic cells.
Side effects : hypoglicemicemia.
Initial dose 0,5 mg every timt before
meals. Max dose 16 mg/day

Nateglinide
Stimulates insulin secretion by
blocking ATP-sensitive potassium
channels in pancreatic cells.
Dose of 3x 120 mg, 1 to 10 minutes
before a meal.
Side effects : hypoglicemia (more
rare)

Thiazolidinediones
Troglitazone (withdrawn because
causing severe hepatic toxicity),
Rosiglitazone, and Pioglitazone.
Can be combined with insulin or other
classes.
Side effects : hepatotoxicity, anemia,
weight gain, edema, and plasma
volume expansion
Pioglitazone Dose : 1x 15-30 mg/day.

Mechanism of action
Thiazolidinediones are selective agonists
for nuclear peroxisome proliferator
activated receptor- (PPAR) activates
insulin-responsive genes that regulate
carbohydrate and lipid metabolism.
Increasing insulin sensitivity in peripheral
tissue, lowering glucose production by the
liver, increasing glucose transport into
muscle and adipose tissue

-Glucosidase Inhibitors
Acarbose, Miglitol.
Inhibition of -glucosidase enzyme in
the intestinal brush border slows
the absorption of carbohydrates.
Used in combination with other oral
antidiabetic agents and/or insulin.
SIDE EFFECTS : malabsorption,
flatulence, diarrhea, and abdominal
bloating.

Mechanism of Actions
Acarbos
e

Dosing of Acarbose
GLUCOBAY : acarbose 50, 100 mg.
Initial dose 3x 50 mg, can be increase
after 4-8 weeks 3x 100-200 mg