:Treatment of diabetes

Life style modification 

Insulin 

Oral hypoglycemic agents 

Life style modification

Diet control 

Exercise 

Smoking cessation 
DIET CONTROL
All diabetic patients should be on 
.diet control

Diet control is a must either the 

patient is taking insulin or oral
.therapy

. Over weight should be reduced 

DIET CONTROL
Diet control should be tried at 
first before the next step
[insulin or tablets] especially in
obese patients, When diet fails
.drugs are indicated
 DIET CONTROL
The diet for a diabetic patient is 
not so different from the healthy
.diets for the whole population

Simple sugars Carbohydrate [as 

sucrose], should be limited for the
.diet of diabetic patients
DIET CONTROL
Carbohydrate content should be in 
a fiber-rich diet [for example
.fruits containing fibers as apples]
because the fiber content of ..…
diet delays absorption of
carbohydrates avoiding the rapid
.elevation of blood glucose levels
DIET CONTROL
: Calories
Calories should be tailored to the •
.need of the patient
:Diet should contain
Carbohydrates → 50 - 55% 
Fat→ 30-35% 
Protein →10 - 15% 
Indication of Insulin
Type 1 diabetes 
Unstable diabetes 
.Type 2 diabetes failed on SUs 
Pregnant diabetic patients 
Surgery (all diabetic patients) 
Diabetic coma 
Oral hypoglycemic agents

Biguanides 

Sulfonylureas 

α- glucosidase inhibitors 

Thiazolidinediones 

Prandial glucose regulator 

Biguanides
Biguanides are derivatives of the 
antimalarial agent Chloroguanide.
Which is found to have hypoglycemic
.action
The most commonly used member of 
.biguanides is Metformin [Cidophage]
Biguanides
:Indication 

Type 2 diabetes failed on diet 

Metformin can be given alone or in 

combination with sulfonylureas or

Insulin
Biguanides
Mode of action
Biguanides [Metformin] is an
Antihyperglycemic and not
.Hypoglycemic agent
It does not stimulate pancreas to secrete 

insulin and does not cause hypoglycemia

.(as a side effect) even in large doses
Also it has no effect on secretion of 

.Glucagon or Somatostatin
Biguanides
:Mode of action 
Decreases the intestinal 
absorption of CHO
Increases glucose uptake (GLUT 4) 
Increases glucose utilization 
(glycogensynthase)
Increases glycolysis via anaerobic 
pathway (lactic acidosis)
Biguanides
:Pharmacokinetics
Metformin is well absorbed 
from small intestine, stable,
does not bind to plasma
proteins, excreted unchanged
.in urine
Half life of Metformin is 1.5 - 
4.5 hours, taken in three doses
with meals
Biguanides
:Side effects
.occur in 20-25 % of patients 
include.. Diarrhea, abdominal 
discomfort, nausea, metallic
taste and decreased absorption
.of vitamin B12
Biguanides
Contraindications
Patients with renal or hepatic 
.impairment
.Past history of lactic acidosis 
.Heart failure, Chronic lung disease 
These conditions predispose to ..
increased lactate production which
.causes lactic acidosis which is fatal
SULFONYLUREAS

SUs., have been discovered during 

.the 2nd. World war (sulfonamide)

SUs are drugs that used orally to 

control blood glucose levels of type
.2 diabetes
SULFONYLUREAS
:Types 
,First generation 

Chlorpropamide (Pamidin) 
Tolbutamide (Diamol) 
,Second generation 

Gliclazide (Diamicron) 
Glibenclamide (Daonil) 
Glipizide (Minidiab) 
,Third generation 

Glimepiride (Diabride) (Amaryl) 

SULFONYLUREAS

:Mechanism of action
Pancreatic effect 
Extra-pancreatic effect 
SULFONYLUREAS
:Pancreatic effect
Increase insulin release from •

pancreas
Suppress secretions of Glucagon •
SULFONYLUREAS
:Extra pancreatic effect 
Increases the number of insulin 
receptors
Increases post-receptor insulin 
sensitivity
Increases glucolysis 
Increases glycogen storage in 
muscle and liver
Decreases the hepatic output of 
glucose
SULFONYLUREAS
:Pharmacokinetics 
They are effectively absorbed 
.from gastrointestinal tract
Food can reduce the absorption of 
. sulfonylurea
Sulfonylureas are more effective 
when given 30 minutes before
.eating
Plasma protein binding is high 90 – 
.99 % .. mainly bind to albumen
SULFONYLUREAS
:Pharmacokinetics 
1st generation members have 
.short half lives
2nd generation is administered 
.once, twice or several times daily
3rd generation is administered 
.once daily
SULFONYLUREAS
:Pharmacokinetics
All sulfonylurea are metabolized by 
liver and their metabolites are
excreted in urine with about 20 %
.excreted unchanged
Sulfonylurea should be administered 
with caution to patients with either
.renal or hepatic insufficiency
SULFONYLUREAS
: Adverse Reactions
Very few adverse reactions [4 %] in the 
first generation and rare in the 2nd and
.3rd generation
SUs may induce hypoglycemia especially 
in elderly patients with impaired hepatic
or renal functions-These cases of
hypoglycemia are treated by I/V glucose
.infusion
SULFONYLUREAS
: Adverse Reactions
First generation may induce other 
side effects as …nausea and
vomiting & dermatological
reactions
These side effects are fewer in…
the 2nd generation and rare in the
.3rd generation
SULFONYLUREAS
:Drug interactions
Some drugs may enhance or 
suppress the actions of
sulfonylureas Either by
:affecting
Their metabolism and excretion 
The concentration of free 
sulfonylureas in plasma through
competing them on plasma
.proteins
Drug – Drug interaction

NSAIDs  Barbiturates 
Salicylates  Thiazide and loop 
diuretics
Sulfonamide 
Sympathomimetics 
ß-blockers 
Corticosteroids 
Chloramphenicol 
Oestrogen / 
Diazepam  Progesterone
MAOI  combinations
SULFONYLUREAS
: Contraindications 
Type 1 DM 

.Pregnancy and Lactation 

Significant hepatic or renal 

.failure
α Glucosidase Inhibititor

Acarbose (Glucobay)
Indicated for type 2 
diabetes
In addition with diet
In addition with other anti-
diabetic therapies
Acarbose (Glucobay)
:Mode of action 
Poorly absorbed 1% (act locally in 
G.I.T.)
Inhibits α glucosidase, so inhibits 
CHO degradation
:Dose 
50mg to 100mg 3 times daily 
before meals
Acarbose (Glucobay)
:Side effects 
Flatulence (77%) 
Diarrhea 
Abdominal pain (21%) 
Decreased iron absorption 
Thiazolidenedione

Rosiglitazone (Avandia)

Pioglitazone (Actos)
Thiazolidenedione
:Mode of action 
Insulin sensitizer (increase insulin 
sensitivity in muscle, adipose
tissue & liver)
They are not insulin secretagogues 
(Not insulin releasers)
Thiazolidenedione
:Drawbacks 
They are not effective alone in case 
of severe insulin deficiency and should
be combined with sulfonylurea or
metformin or both
:Side effects 
Hepatotoxicity 

weight gain 

Dyslipidaemia (increases LDL) 

Prandial glucose regulators
(Meglitinide)
:Example 
Repaglinide, Novonorm 
(NovoNordisk)
:Rational 
Fast acting, short duration non- 
sulfonylurea
Designed to minimize mealtime 
blood glucose peaks
Repaglinide, Novonorm
:Mechanism of action 
Stimulation of pancreatic insulin 
release by closing ß-cells KATP
channels
Very rapid onset of action and 
short duration (TMAX = 1 hour,
metabolized by liver T1/2 = 70
minutes)
No hypoglycemic metabolites 
Repaglinide, Novonorm
:Clinical efficacy 
Improves postprandial glycemia 

Less effective in decreasing fasting 

blood glucose levels and HbA1C
:drawbacks 
Fails to provides a stable 24 hours 
blood glucose control
Complicated dosage style (3-8 
tablets/daily)
How to adapt the dosage to the meal 
?volume