Glucovance Helps with Treatment of Type 2 Diabetes
Brand Name: Glucovance
Active Ingredient: metformin / glyburide
Indication: Treatment of type 2 diabetes
Company Name: Bristol-Myers Squibb Company
Availability: Approved by FDA on July 31, 2000
Introduction
The drugs metformin and glyburide are commonly used by people with type 2 diabetes to control blood glucose levels. Individually the agents may or may not be effective. But together they pack a synergistic punch. A new combination of metformin and glyburide in a single tablet (250 mg metformin and 1.25 mg glyburide), manufactured by Bristol-Myers Squibb under the trade name Glucovance, helped people with type 2 diabetes achieve greater blood glucose control than either pill alone, reported investigators at the 60th annual meeting of the American Diabetes Association in June 2000. Glucovance is currently under review by the FDA.
How It Works
Metformin increases insulin action in peripheral tissues and reduces hepatic glucose output by inhibiting gluconeogenesis. Metformin may also reduce plasma glucose by decreasing the absorption of glucose from the small intestine.
Glyburide is a sulfonylurea that causes hypoglycemia by stimulating insulin release from pancreatic beta cells. Sulfonylureas may also further increase insulin levels by reducing hepatic clearance of the hormone.
Clinical Study Results
A total of 806 people with type 2 diabetes age 60 and older were randomized into multicenter, double-blind, placebo-controlled trials. Patients received either placebo, 2.5 mg glyburide, 500 mg metformin, 250 mg/1.25 mg metformin/glyburide, or 500 mg/2.5 mg metformin/glyburide, and were followed for 20 weeks. At the end of the study period, 66% of the 250 mg/1.25 mg metformin/glyburide group and 72% of the 500 mg/2.5 mg metformin/glyburide group achieved HbA1C levels of less than or equal to 7%, compared to 20% of patients taking placebo, 60% of those on glyburide alone, and 50% of those taking metformin alone.
Subjects in both metformin/glyburide groups also demonstrated significantly larger mean decreases in absolute postprandial glucose (-60.7 mg/dL for the 250mg/1.25 mg group and -58.8 mg/dL for the 500 mg/2.5 mg group) compared to patients taking placebo (+4.5 mg/dL), glyburide (-42.4 mg/dL), or metformin (-40.3 mg/dL) alone. Subjects taking metformin/glyburide also experienced larger mean increases in absolute 2-hour postprandial insulin (29.7 mU/ml for the 250mg/1.25 mg group and 25.0 mU/ml for the 500 mg/2.5 mg group) compared to patients taking placebo (0.9 mU/ml), glyburide (15.1 mU/ml), or metformin (4.0 mU/ml) alone. Finally, subjects in both metformin/glyburide groups also demonstrated significantly larger mean decreases in fasting plasma glucose (-41.5 mg/dL for the 250 mg/1.25 mg group and -40.1 mg/dL for the 500 mg/2.5 mg group) compared to patients taking placebo (+4.6 mg/dL), glyburide (-35.7 mg/dL), or metformin (-21.2 mg/dL) alone.
Adverse Events
Glucovance-related adverse events were minor and included diarrhea, nausea, upset stomach, and hypoglycemia. Patients taking the 250 mg/1.25 mg metformin/glyburide combination had fewer gastrointestinal side effects than patients taking metformin and fewer symptoms of hypoglycemia than those taking glyburide. Patients taking the 500 mg/2.5 mg metformin/glyburide combination reported more symptoms of hypoglycemia than patients taking glyburide, establishing the 250 mg/1.25 mg dosage as the optimal dosage of Glucovance.