Oral Hypoglycemic Drugs

Heider SH. AL-QassamMSc.PH. & TH.

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 2Type 1—patient's βcells are

destroyed this willcause absolute insulin deficiency

Type 2ــــ patient secretes insufficient amounts of insulin and insulin receptors are resistant to existent circulating insulin

Diabetes Mellitus

Oral Hypoglycemic Drugs

I. Insulin Secretagogu

es

Sulfonylureas

Meglitinide analogs

II. Insulin Sensitizers

Biguanides

glitazones

III.α-Glucosidase Inhibitors

IV.Dipeptidyl Peptidase-IV

Inhibitors

V.Incretin Mimetics

(mechanism of action) :A.Increase release of insulinB.Decrease production of glucose in the liverC.Increase the number of insulin receptorsD.Effective only if have functioning beta cellsE.Primary side effect is hypoglycemia and weight gainF.These drugs include glibenclamide, glipizide, and glimepiride .

I.Sulfonylureas

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

II.Meglitinides

(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

III.Biguanides

(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

IV.Glitazones

Include acarbose and miglitol (mechanism of action): inhibit alpha-

glucosidase 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

Alpha glucosidase Inhibitors

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

Incretin Mimetics

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

newOral Agents: Dipeptidyl Peptidase-IV Inhibitors

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