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

Oral Hypoglycemic Drugs II. Insulin Sensitizers Insulin Secretagogues Sulfonylureas Biguanides Meglitinide analogs glitazones III.α-Glucosidase Inhibitors IV.Dipeptidyl Peptidase-IV Inhibitors V.Incretin Mimetics

I.Sulfonylureas (mechanism of action) : Increase release of insulin Decrease production of glucose in the liver Increase the number of insulin receptors 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 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

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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