ORAL HYPOGLYCAEMIC DRUGS

Classification
Stimulate insulin release
(insulin secretagogues)hypoglycemic

Name of drug
a) Sulfonylureas :
Tolbutamide
Glyburide
b) Meglitinides :
Repaglinide

Increase insulin responsiveness

(insulin sensitizers-increase
sensitivity of peripheral tissues
to insulin)-euglycemic

a) Biguanides :
Metformin
b) Thiazolidinediones :
Rosiglitazone

Modify intestinal absorption of

carbohydrate-euglycemic

a) Alpha-glucosidase inhibitors :
Acarbose

Newer drugs-euglycemic

a) Amylin analog (Pramlitide)

b) DPP-4 inhibitor (Sitagliptin)
c) Incretin mimetics (Exenatidea)

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DRU
G

MOA

Sulfonylureas

Meglitinide
s

Biguanide
s

Thiazolidin
ediones

Alphaglucosida
se
inhibitor

DPP-4
(NEW

1) 1st gen :
Tolbutamide
(shorter
duration of axn)
2) 2nd gen :
Glyburide
(longer
duration of
axn)-mostly
prescribedless A/E & DDI
Binds to sulfonylurea R
(a/w ATP-sensitive
potassium channel)
Blocks ATP-dependent
K+ channel inhibits
K+ efflux
membrane
depolarization Ca2+
chn opens + Ca2+
influx insulin
secretion

Repaglinide

Metformin
-antihyperglycem
ic
(euglycemicnormalize
glucose lvl,
never lowers
it)

Rosiglitazone

Arcabose

Sitagli

Same with
sulfonylureas

-Reduces
hepatic
glucose
production
(gluconeoge
nesis)
through
activation of
liver enzyme
AMPactivated
protein
kinase
-Improves
insulin
sensitivity in
periphery
(lowers
insulin
resistance)
-Reduces
intestinal
absorption of
glucose

Binds to
PPAR
(Peroxisome
Proliferatoractivated R
gamma)steroid
hormone
nuclear R
activated
PPAR
migrate to
DNA
activation of
transcription
of genes
involved in
glucose & FA
metabolism :
-increase
glucose upt8
in ms & AT
-inhibits
hepatic
gluconeogene
sis
-increase
lipogenesis

- Starch
blockers
(delay
glucose
absorption
& reduces
postprandia
l glucose)gv b4 meal.
If after,
carbs
already
absorbed

- Inhib
(dipep
peptid
enzym
enhan
hormo

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Competitiv
ely inhibit
intestinal
membranebound
alphaglucosidase
(enzyme
for
conversion
of complex
starch to
monosacc
that can be
transported
into
bloodstrea
m)

-Food
GLP-1
L-cells
ileum
> sup
glucag
secret
> stim
insulin
> red
intake
> slow
empty
> long
increa
mass

PK

-Met : liver cyt P450

-Highly bound to
plasma proteins

DDI

Hypoglycemic axn
will increase in :-displacement from
plasma prot :
salicylates, warfarin
-decreased urinary
excretion : salicylates,
allopurinol (compete w
same transportation to
kidney tubule)
-decreased hepatic

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1) rapidly
absorbed &
very fast
onset (shortacting)
2) short
duration of
axn (4-7 hr)
3) met : in
liver
4) post
prandial effect
(administered
just b4 meal
bcoz short pd
of axn)
5) shorter axn
w less
hypoglycaemi
a
-

-Absorbed in
GIT
-Not bound
to plasma
prot
-Not
metabolized
-Excreted w
the urine
-More
preferable

- rapidly
absorbed
- highly
protein-bound
- metabolized
in liver
- administered
once/twice
daily
- slow onset &
offset of axn
over
weeks/months
(bcoz involve
gene
transcription)

Well-a
GIT

USE
S

A/E

CI

met : MAO inh,

warfarin (increased
toxicity)
1) DM T2
2) Ineffective in T1
(B cells not
functioning-no
insulin)

-Hypoglycemia d/t
hyperinsulinemia
-Wt gain

a) Hepatic & renal

insufficiency
(increase risk of

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1) DM T2
2) Allergy
to
sulfony
lureas
3) Should
take
just b4
meal

Hypoglycemia
(d/t fast onset
& short
duration of
axn,
hypoglycemia
is a risk if the
meal is
delayed/skipp
ed/contains
inadequate
carbs)
-Wt gain
Hepatic &
renal
insufficiency

-Wt loss in
T2 DM w
obesity
-Insulinsparing
agent &
doesnt
increase
wt/cause
hypoglycemi
a
-Why tx of
choice in
newly
diagnosed
T2 DM?
(because
high insulin
production at
early onset
of dx,
hyperinsulin
emia.
Therefore
need to
improves
body
responds to
insulin to
prevent high
glucose lvl)
-Diarrhea &
dyspepsis
(up to 30%
of pts)
-Lactic
acidosis
(rare but
fatal)

- In highly
insulinresistant pts
(T2 DM)
- Its is
euglycemics

-Weak
antidiabetic
effect
-DM T2 w
conjunction
w other
antidiabetic
drugs
-Must t8 at
start of
main meals
to hv max
effect.

- Used
metfor
- Once

- Fluid
retention
- Risk of
hepatotoxicity
(monitor liver
fxn)
- Wt gain

GI effects :-

Well to

-flatulence
-diarrhea
-abdominal
pain

-Heada
-Diarrh

Can increase
the risk of
lactic

- HF (d/t fluid
retention)
- Pregnancy

WHY? :Bcoz no
carbs
absorption.
Carbs are
substrate
of normal
flora
-

hypoglycaemia)
b) Pregnancy &
lactation :
Teratoge
nic
agent
(categor
y C)
Neonata
l
hypogly
caemia
(lactatio
n never
use)

acidosis :
-HF
-Kidney
disorders
-Lung dz
(hypoxia
leads to
lactate
production)
-Liver dz

- Hepatic
failure

THE OTHER NEWER DRUGS

1) Amylin analog (Pramlintide)

-Amylin : Co secreted w insulin from B

cells
Prolongs gastric emptying time
Reduces postprandial glucagon
secretion
Reduces food intake (centrallymediated appetite suppression)
-Pramlintide : Aminomimetic
Delays gastric emptying
Reduces postprandial glucose
Improves satiety

2) Incretin mimetics (ExenatideByetta)-synthetic exendin-4

3) Renal Na+ glucose transporter

inhibitors (Sergliflozin)-Inh of
SGLT2

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-Uses :
Adjunct mealtime insulin therapy
in T1 & T2 DM
Inject SCly b4 meal
-GLP-1 analog : Increases insulin secretion
Increases B cell growth
Slows gastric emptying
Reduces food intake
Selective inh of Na+ glu
cotransporter 2
Increases excretion of glucose w
urine
Predisposes to UTI (glucose is
substrate for microorgs growth)

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