Oral Hypoglycemic Drugs
Heider SH. AL-Qassam
MSc.PH. & TH.
Diabetes Mellitus
 Chronic systemic disease characterized
by metabolic abnormalities
 Disorder of carbohydrate metabolism
 Results from inadequate production of
insulin
Diabetes Mellitus
 Characterized by glucosuria and
hyperglycemia
 Two forms—Type 1 and Type 2
 Type 1—patient's βcells are destroyed
this willcause absolute insulin deficiency
 Type 2‫ ــــ‬patient secretes insufficient
amounts of insulin and insulin receptors
are resistant to existent circulating
insulin
Oral Hypoglycemic Drugs
II. Insulin
Sensitizers
I. Insulin
Secretagogues
Sulfonylureas
Biguanides
Meglitinide
analogs
glitazones
III.α-Glucosidase
Inhibitors
IV.Dipeptidyl
Peptidase-IV
Inhibitors
V.Incretin Mimetics
I.Sulfonylureas
(mechanism of action) :
A. Increase release of insulin
B. Decrease production of glucose in the liver
C. Increase the number of insulin receptors
D. Effective only if have functioning beta cells
 Primary side effect is hypoglycemia and weight
gain
 These drugs include glibenclamide, glipizide,
and glimepiride .
II.Meglitinides
 Nateglinide and repaglinide are nonsulfonylureas that
lower blood sugar by stimulating pancreatic secretion
of insulin
 In contrast to the sulfonylureas, the meglitinides have
a rapid onset and a short duration of action
 They are categorized as postprandial glucose
regulators
 Monotherapy or in combination with metformin
 Should be taken 1 to 30 minutes before a meal
 Side effects hypoglycemia and weight gian
 caution in patients with hepatic impairment
III.Biguanides
 (mechanism of action): increases the use of glucose
by muscle and fat cells, decreases hepatic glucose
production, and decreases intestinal absorption of
glucose
 Does not cause hypoglycemia
 May be used alone or in combination
 Side effects include GIT disturbance and lactic acidosis
 Contraindicated in liver or renal impairment. Can
result in lactic acidosis.
 This group include metformin
IV.Glitazones
 (mechanism of action):Decrease insulin resistance.
Through binding with PPAR lead to regulation adipocyte
production and secretion of fatty acids as well as glucose
metabolism, resulting in increased insulin sensitivity in
adipose tissue, liver, and skeletal muscle
 Side effects include weight gain, headache and anemia
 Contraindicated in patients with liver disease and acute
MI
 May be used as monotherapy or in combination with
insulin, metformin or a sulfonylurea
 These drugs include Pioglitazone and rosiglitazone
Alpha glucosidase Inhibitors
 Include acarbose and miglitol
 (mechanism of action): inhibit alphaglucosidase enzymes (maltase, amylase,
sucrase) in GI tract. Delays absorption of
complex CHO and simple sugars
 Can be combined therapy with sulfonylurea
 Contraindicated in malabsorption, severe renal
impairment
 Side effects include bloating and diarrhea
Incretin Mimetics
 Exenatide is an incretin mimetic with a polypeptide
homologous to GLP-1
 It is improves glucose-dependent insulin secretion
,slows gastric emptying time, decreases food intake,
decreases glucagon secretion, and promotes βcell
proliferation
 It must be administered subcutaneously
 Side effects include nausea, vomiting, and diarrhea
newOral Agents: Dipeptidyl
Peptidase-IV Inhibitors
 Sitagliptin is an orally active dipeptidyl peptidase-IV
inhibitor used for the treatment of patients with
Type 2 diabetes
(Mechanism of action)
 inhibits the enzyme DPP-IV, which is responsible for
the inactivation of incretin hormones, such as
glucagon-like peptide-1 (GLP-1).
 Prolonging the activity of incretin hormones results
in increased insulin release in response to meals
 Adverse effects include nasopharyngitis and
headache
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