ORAL ANTI-DIABETIC AGENTS 2012 SULFONYLUREAS GLIBENCLAMIDE, GLIPIZIDE, GLICAZIDE Secretion of insulin from beta cells.

s. can lower plasma glucose by up to 25% and lower HbA1C by about 1.5% block ATP sensitive potassium channels on the beta cell plasma membrane result in the release of stored insulin in response to glucose NON-SULFONYLUREAS REPAGLINIDE, NATEGLINIDE Stimulate secretion of insulin from beta cells in a rapid, brief pulse and bind to a different site within the SU receptor Given 15 min. before a meal, effectively control PP hyperglycemia Less tendency to produce hypoglycemia due to short duration Can be combined with metformin, TZDs or AGIs Hypoglycemia, weight gain In patients with sulphonylurea allergy Preferred in elderly due to the short duration BIGUANIDES METFORMIN Act by sensitivity to insulin insulin resistance Insulin sparing It can lower plasma glucose by up to 20% as first line drug especially in overweight / obese patients hepatic gluconeogenesis & glycolysis in muscle glucose absorption from GIT

MECHANISM OF ACTION

ADVERSE EFFECT USES

OTHER CHARACTERISTICS

hypoglycemia weight gain of about 2kg combined with other OAD agents or insulin to improve glucose control. First line treatment with glibenclamide results in earlier monotherapy failure drugs should be taken 30 minutes before meal Glibenclamide should be stopped if renal impairment develops and should not be used in the elderly(>65 years) drugs that can displace them (NSAIDs, antithyroid drugs, sulpha drugs, anticoagulants) can increase the risk of hypoglycemia

Anorexia, GI upset, lactic acidosis (rare) Obese type 2 DM pts. (as no weight gain) In insulin resistance ( insulin resistance )

Additive hypoglycemia if given with sulfonylureas. Higher risk of prolonged hypoglycemia when repaglinide is combined with gemfibrozil Combination is contraindicated

Euglycemic agents - Do not cause hypoglycemia No weight gain, cause weight loss Should not be used in impaired renal function, liver cirrhosis, CCF, Chronic respiratory disease, vascular disease and conditions that can cause lactic acidosis

ORAL ANTI-DIABETIC AGENTS 2012 All patients must be taught to recognize symptoms of hypoglycemia and its management.

MECHANISM OF ACTION OF METFORMIN

ORAL ANTI-DIABETIC AGENTS 2012 THIAZOLIDINEDIONES ROSIGLITAZONES, PIOGLITAZONE Reduce hepatic output of glucose by inhibiting gluconeogensis Increase peripheral uptake GLUCOSIDASE INHIBITOR ACARBOSE, MIGLITOL competitive inhibitor of -glucosidase, an intestinal enzyme, metabolising complex carbohydrates and postprandial hyperglycemia by delaying glucose absorption. body weight & plasma triglycerides & insulin sensitivity diarrhea flatulence abdominal distention (due to increased delivery of carbohydrates to the large intestine) As adjuvant to diet & other OADA in obese diabetics For type 1 DM DPP-4 INHIBITOR SITAGLIPTIN increased Incretin levels (GLP-1 and GIP) increases insulin secretion and decreases gastric emptying. GLP-1 ANALOGUE EXENATIDE Given parenterally just before breakfast and dinner Progressive weight loss is (because of its effect on satiety and delay in gastric emptying)

MECHANISM OF ACTION

ADVERSE EFFECT

weight gain and fluid retention Contraindicated in pregnant and breastfeeding women and in children Enhance the effectiveness of endogenous insulin and reduces the amount of exogenous insulin Reduction of blood glucose reduction in circulating insulin and free fatty acids Decline triglycerides

Minimal risk of hypoglycemia and no weight gain

Nausea

*can be minimized by starting a low dose*

USES

Type 2 DM

ORAL ANTI-DIABETIC AGENTS 2012 OTHER CHARACTERISTICS Can be combined with other OAD agents (SUs, metformin, or DPP-4 inhibitors) Less effective than metformin or SU, reducing HbA1c by 0.50.8% Reduction of dose in renal impairment Generally well tolerated Can be added to metformin and/or SU Starting dose is 5microgram BD Not a substitute for insulin

MECHANISM OF ACTION OF THIAZOLIDINEDIONES