Biguanides are derivatives of the
antimalarial agent Chloroguanide. Which is
found to have hypoglycemic action. The most
commonly used member of biguanides is
Type 2 diabetes failed on diet Metformin can
be given alone or in combination with
sulfonylureas or Insulin
Mode of action
(Metformin) is an
Antihyperglycemic and not Hypoglycemic
► 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.
► Decreases the intestinal absorption of CHO
► Increases glucose uptake (GLUT 4)
► Increases glucose utilization
► Increases glycolysis via anaerobic pathway
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.
► Occur in 20-25 % of patients.
include.. Diarrhea, abdominal discomfort,
nausea, metallic taste and decreased
absorption of vitamin B12.
► Patients with renal or hepatic
► Past history of lactic acidosis.
► Heart failure, Chronic lung disease.
These conditions predispose to increased
lactate production which causes lactic
acidosis which is fatal.
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.
► First generation: Chlorpropamide
► Second generation: Gliclazide,
► Third generation:
Mechanism of action:
||Extra pancreatic effect:
insulin release from pancreas
► Suppress secretions of Glucagon
the number of insulin receptors
post-receptor insulin sensitivity
glycogen storage in muscle and liver
► Decreases the
hepatic output of glucose
► They are effectively absorbed from
► Food can reduce the absorption of
Sulfonylurea are more effective when given
30 minutes before eating.
► Plasma protein binding is high 90 – 99 % ..
mainly bind to albumen.
► 1st generation members have short half
► 2nd generation is administered once, twice
or several times daily.
► 3rd generation is administered once daily.
► 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
► Very few adverse reactions
(4 %) in the
first generation and rare in the 2nd and 3rd
► SUs may induce hypoglycemia especially in
elderly patients with impaired hepatic or
renal functions-These cases of
are treated by I/V glucose infusion.
► First generation may induce other side
effects as: Nausea and vomiting &
"These side effects are fewer in the 2nd
generation and rare in the 3rd generation"
Some drugs may enhance or suppress the
actions of sulfonylurea Either by
► Their metabolism and excretion
► The concentration of free sulfonylureas in
plasma through competing them on plasma
|Enhancing SUs Action
||Suppress SUs Action
Thiazide and loop diuretics
Oestrogen / Progesterone combinations
Type 1 DM
Pregnancy and Lactation.
Significant hepatic or renal failure.
|α- glucosidase inhibitors
Indicated for type 2 diabetes
In addition with diet In addition with other
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
|► Flatulence (77%)
||► Diarrhea Abdominal pain (21%)
||► Decreased iron absorption
Mode of action:
► Insulin sensitizer
(increase insulin sensitivity in muscle,
adipose tissue & liver)
► They are not insulin
secretagogues (Not insulin releasers)
► They are not
effective alone in case of severe insulin
deficiency and should be combined with
sulfonylurea or metformin or
► Weight gain
Rational: Fast acting, short duration
non-sulfonylurea Designed to minimize
mealtime blood glucose peaks
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)
► Improves postprandial
► Less effective in decreasing
fasting blood glucose levels and HbA1C
► Fails to provides a stable 24
hours blood glucose control
dosage style (3-8 tablets/daily)
► How to
adapt the dosage to the meal volume?