Glucovance FDA approval

The first combination oral antihyperglycemic agent was recently approved by the Food and Drug Administration (FDA). Glucovance™, a combination of glyburide and metformin, is manufactured by Bristol-Myers Squibb. It is FDA-approved as first-line therapy for patients with Type 2 diabetes mellitus (DM) whose glucose is not controlled with diet and exercise. It can also be used as second-line therapy for patients whose blood glucose levels are not controlled with either a sulfonylurea or metformin alone.

Each individual component of Glucovance™ has its own unique mechanism of action. Glyburide, a sulfonylurea, lowers blood glucose by stimulating the pancreas to secrete insulin. Metformin, a biguanide, works by decreasing gluconeogenesis and intestinal glucose absorption, as well as enhancing insulin sensitivity.

Some common adverse effects associated with Glucovance™ include diarrhea, upper respiratory infection, lightheadedness, dizziness, shaking, hunger, and headache. Additionally, due to the metformin component, Glucovance™ may cause lactic acidosis, a rare but serious adverse effect. The risk of lactic acidosis increases with patient age and degree of renal insufficiency. To avoid lactic acidosis, it is recommended to 1) monitor renal function, 2) use the lowest dose possible of the metformin component, and 3) do not initiate its use in patients 80 years of age or older. Glucovance™ also has the potential to cause hypoglycemia because it stimulates insulin secretion. The risk is greatest in patients with decreased caloric intake, those taking concurrent glucose-lowering medications, or those ingesting alcohol.

Caution should be exercised when initiating or discontinuing agents that may cause hypoglycemia (e.g., nonsteroidal anti-inflammatory agents, warfarin, beta blockers) or hyperglycemia (e.g., diuretics, steroids, phenytoin, estrogens, calcium channel blockers) while patients are receiving Glucovance™. Drug interactions may also occur between metformin and agents that are excreted by renal tubular secretion (e.g., digoxin, procainamide, amiloride, quinidine, vancomycin).

Glucovance™ is contraindicated when serum creatinine levels are 1.5 mg/dL or higher in males or 1.4 mg/dL or higher in females, hypersensitivity to either component, kidney dysfunction, congestive heart failure, and acute or chronic metabolic acidosis.

If the patient's current combination therapy (e.g., glyburide [or another sulfonylurea] plus metformin) is changed to Glucovance™, the dose should not exceed the daily dose of sulfonylurea and metformin already being taken. See Table 1 for specific dosing recommendations of Glucovance™.

There are three tablet strengths of Glucovance™ available: 1.25 mg/250 mg (glyburide/metformin), 2.5 mg/500 mg, and 5 mg/500 mg. Based on the average wholesale price (AWP), the costs are approximately $0.66, $0.78, and $0.78 per tablet, respectively.

There are advantages for combining glyburide and metformin: 1) lower doses are required for glucose control, 2) fewer adverse effects may occur, and 3) increase in patient acceptance and compliance. In addition, patients should maintain a good diet and exercise program, as well as regular blood glucose monitoring.