Antidiabetic Drugs ================== þ Oral Hypoglycemic Agents - Metformin-biguanide, decreased hepatic glucose output, lowers fasting glucose, rare hypoglycemia - Sulfonylureas—enhance insulin secretion, severe hypoglycemia, esp in the elderly, 1st gen meds such as glyburide, chlorpropamide. Less hypoglycemia with 2nd gen meds such as glipizide - Glinides-stimulate insulin secretion, shorter half-life, less hypoglycemia (repaglinide, nateglinide) - A-glucosidase inhibitors—reduce rate of carbohydrate digestion in small intestine, LOTS GI side effects, lowers post prandial glucose spike (acarbose) - Thiazolidinediones—(TZDs or glitazones) “insulin sensitizers”—SE weight gain, edema, CHF, increased fractures—no rosiglitazone - Glucagon-like peptide-1 agonists (GLP-1), exenatide, SQ, augments glucose mediated insulin secretion, suppresses glucagon excretion, slows gastric motility - Amylin agonists (pramlintide)- synthetic analogue of amylin, SQ, slows gastric emptying, inhibits glucagon—decreased post prandial glucose elevations - Dipeptidyl peptidase 4 inhibitors—block degradation of GLP-1 and GIP (incretins), thus increasing glu med insulin secretion (sitagliptin) þ Insulin þ Early Treatments - insulin and sulfonylureas, raise plasma insulin levels þ Rezulin (Troglitazone) - withdrawn March 22, 2000 as more hepatotoxic than resiglitazone (Avandia) and pioglitazone (Actos). - dose 200-400 mg with meals. - helps circulating insulin convert glucose - no hypoglycemia - lowers triglycerides and BP - can use in combination with other agents - may need to decrease insulin dose - may cause headache, dizzyness, diarrhea, edema - very expensive - Rezulin (troglitazone) was formally admitted to the Hospital Formulary. It is unique in that it belongs to a brand new class of oral antidiabetic agents. It is a thiazolidinedione that works systemically to reduce peripheral insulin resistance without stimulating insulin secretion. Troglitazone also works to a lesser degree by reducing excessive hepatic glucose production. The drug will reduce insulin requirements in insulin resistance states. It is indicated for use in patients with type II diabetes whose hyperglycemia is inadequately controlled despite insulin therapy of over 30 units per day given as multiple injections. Troglitazone has been studied in hyperinsulinemic nondiabetic patients with normal and impaired glucose tolerance (IGT). Therapy with troglitazone results in a substantial improvement in insulin resistance as demonstrated by a marked reduction in basal and postprandial hyperinsulinemia. Troglitazone does not have an effect on endogenous insulin secretion and, accordingly, has not been associated with hypoglycemia in nondiabetic patients. --from Mercy Pharmacy and Therapeutics Update, 6/97 þ Glucovance - fixed-dose combination of Glucophage (metformin) and glyburide (Micronase, DiaBeta, Glynase) - 1.25mg/250 mg, 2.5 mg/500 mg, 5 mg/500 mg (glyburide/metformin) þ Glucophage (metformin) - old drug, used for centuries in herbal form (from Galega officinalis, French Lily) - usually 500 BID - decreases GI absorption - decreases hepatic glucose production - increases peripheral glucose disposal - no hypoglycemia - no weight gain - decreases triglyceride and cholesterol - more expensive than sulfonylureas - may cause severe (3:1000 patient years) lactic acidosis, nausea, diarrhea, metallic taste -phenformin taken off the market due to higher risk of same problem. This is an interaction with renal insufficiency, anyone with Cr>= 1.4 shouldn't be on it. Can also cause acidosis with OD or accentuate acidosis from other causes. - stop in severely ill who might develop lactic acidosis. - problems with IV contrast þ Precose (acarbose) - dose 100 mg TID - lowers postprandial glucose, not fasting glucose - inhibits brush border polysaccharide enzymes, blocks oral agents given for hypoglycemia - flatulence - decreased with guar crisp bread (?) þ Repaglinide (Prandin)