DRUGS OF CHOICE
The following classes of agents may be used alone or in combination. Sulfonylureas are generally used as initial treatment, but recent data suggest that metformin may be the preferred first medication in obese patients. If one drug does not produce adequate control, a drug from a different class should be added. If two agents are not adequate, insulin might be the next best addition.
- Biguanides
– Metformin (Glucophage) 500-850 mg bid-tid - Sulfonylureas
– Glimepiride (Amaryl) 1-8 mg/d in 1 dose
– Glipizide (Glucotrol) 2.5-40 mg/d in 1-2 doses (1st 20 mg in AM)
– Glipizide extended release tablets 5-20 mg/d in 1 dose
– Glyburide (DiaBeta, Micronase) 1.25-20 mg/d in 1-2 doses (1st 10 mg in AM)
– Note: sulfonylureas may be taken with meals except glipizide which should be taken 30 min before meals - Thiazolidinediones
– Pioglitazone (Actos) 15-45 mg qd
– Rosiglitazone (Avandia) 2-4 mg bid. Monitor serum transaminase q 2 mo for 1st year. - a-Glucosidase inhibitors
– Acarbose(Precose)25-100 mg tid
– Miglitol (Glyset) 25-100 mg tid
– Taken at beginning of meals to decrease postprandial glucose peaks. Avoid use in renal insufficiency, inflammatory bowel disease, colonic ulceration or partial bowel obstruction. - Insulin may be used in combination with oral agents. Most often required in late stages of type 2 diabetes mellitus when oral agents fail to control blood glucose. Insulin can be started as 10 units combination intermediate/short acting with evening meal or intermediate (NPH) or insulin glargine at bedtime.
– Rapid-acting insulin: Aspart (Novolog), Glulisine (Apidra), Lispro (Humalog)
– Short-acting insulin: Regular (Humulin R, Novolin R)
– Intermediate-acting insulin: Lente (Humulin L, Novolin L), NPH (Humulin N, Novolin N)
– Long-acting insulin: Glargine (Lantus), Ultralente (Humulin U) - Combinations
– Fixed dose combinations of metformin with glipizide, glyburide, and rosiglitazone are available
Contraindications:
- To oral agents: type I (insulin dependent) diabetes mellitus, ketotic patient, pregnancy, history of specific drug allergy
- Use caution in liver or renal disease and acute infection or stress
Precautions:
- Warn patients of signs of hypo- and hyperglycemia
- Home glucose monitoring (1-4 times/d) recommended for most patients taking insulin
- Avoid metformin in situations which increase risk for lactic acidosis: renal insufficiency, radiocontrast agents, surgery or acute illnesses such as liver disease, cardiogenic shock, pancreatitis or hypoxia. Use caution in CHF, alcohol abuse, elderly or with tetracycline.
Significant possible interactions:
- Drugs which may potentiate sulfonylureas include: salicylates, clofibrate, warfarin (Coumadin), chloramphenicol, ethanol, and ACE inhibitors
- Beta-blockers may mask symptoms of hypoglycemia and delay return to normoglycemia
- Thiazolidinedione pioglitazone may decrease effectiveness of oral contraceptives
- Drugs which bind others in the intestine, such as cholestyramine resin, should be taken at least 2 hours apart from a-glucosidase inhibitors
- Gatifloxacin
ALTERNATIVE DRUGS
- Aspirin recommended for diabetics with known macrovascular disease and those over 40 years old with another risk factor for vascular disease
- First generation sulfonylureas
– Chlorpropamide (Diabinese) 100-500 mg/d in 1 dose
– Tolazamide (Tolinase) 100-1000 mg/d in 1-2 doses
– Tolbutamide (Orinase) 500-3000 mg/d in 2-3 doses - Meglitinides
– Repaglinide (Prandin) 0.5-4 mg before meals tid. May be useful in patients with sulfa allergy or renal impairment who are not candidates for sulfonylureas.
– Nateglinide (Starlix) 60-120 mg before meals tid
