Drug Name: Metaglip (glipizide/metformin HCl)
Company: Bristol-Myers Squibb
Approval Status: Approved October 2002
Treatment for: Type 2 Diabetes

General Information
Metaglip combines glipizide and metformin HCl two prescribed oral antidiabetic agents in a single pill. These agents work in complementary fashion to improve blood sugar in patients with type 2 diabetes.

Metaglip is indicated as initial therapy, as an adjunct to diet and exercise, to improve glycemic control in patients with type 2 diabetes whose hyperglycemia cannot be satisfactorily managed with diet and exercise alone. Metaglip is also indicated as second-line therapy when diet, exercise, and initial treatment with a sulfonylurea or metformin do not result in adequate glycemic control in patients with type 2 diabetes.

Clinical Results
In clinical trials, Metaglip was shown to be more effective at lowering blood sugar levels than either glipizide or metformin used alone in patients with type 2 diabetes. In a 24-week, double-blind, active-controlled, multicenter international clinical trial, patients with type 2 diabetes, whose hyperglycemia was not adequately controlled with diet and exercise alone were randomized to receive initial therapy with glipizide (5 mg), metformin (500 mg), Metaglip (2.5 mg/250 mg), or Metaglip (2.5 mg/500 mg).

After 24 weeks, treatment with Metaglip resulted in significantly greater reduction in Hemoglobin A1c (HbA1c) compared to glipizide and to metformin therapy. Also, Metaglip therapy resulted in significant reductions in Fasting Plasma Glucose (FPG) versus metformin therapy. Increases above fasting glucose and insulin levels were determined at baseline and final study visits by measurement of plasma glucose and insulin for three hours following a standard mixed liquid meal. Treatment with Metaglip lowered the three-hour postprandial glucose AUC, compared to baseline, to a significantly greater extent than did the glipizide and the metformin therapies.

Side Effects
Adverse events associated with the use of Metaglip may include (but are not limited to) the following:

Upper respiratory infection
Diarrhea
Dizziness
Hypertension
Nausea/vomiting
Headache
Musculoskeletal pain
Abdominal pain
Urinary tract infection

Mechanism of Action
Metaglip combines glipizide and metformin hydrochloride, two antihyperglycemic agents with complementary mechanisms of action, to improve glycemic control in patients with type 2 diabetes.

Glipizide appears to lower blood glucose acutely by stimulating the release of insulin from the pancreas, an effect dependent upon functioning beta cells in the pancreatic islets. Extrapancreatic effects may play a part in the mechanism of action of oral sulfonylurea hypoglycemic drugs.

Metformin hydrochloride is an antihyperglycemic agent that improves glucose tolerance in patients with type 2 diabetes, lowering both basal and postprandial plasma glucose. Metformin hydrochloride decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.