Drug Name: Avandamet (rosiglitazone maleate and metformin HCl)
Company: GlaxoSmithKline
Approval Status: Approved October 2002
Treatment for: Type 2 Diabetes

General Information
Avandamet (rosiglitazone maleate and metformin HCl) has been approved as an adjunct to diet and exercise to improve blood sugar control in type 2 diabetes patients who are already treated with combination rosiglitazone and metformin or who are not adequately controlled on metformin alone.

Avandamet, available in oral tablet formulation, is the first treatment to combine this combination of drugs in one pill.

Clinical Results
Clinical studies have been conducted with the combination of rosiglitazone maleate and metformin HCl, as well as with each component alone. These studies have shown that the products are safe and effective in controlling blood sugar levels in type 2 diabetes patients.

No efficacy studies have been conducted for Avandamet tablets. However, Avandamet has been shown to be bioequivalent to co-administered rosiglitazone maleate tablets and metformin hydrochloride tablets.

Side Effects
In clinical trials of rosiglitazone maleate in combination with metformin hydrochloride 2500 mg/day, the following adverse events were reported most frequently:

Upper respiratory tract infection
Diarrhea
Injury
Anemia
Headache
Sinusitis
Fatigue
Back pain
Viral infection
Arthralgia
Hyperglycemia
A small number of people who have been treated with metformin have developed the serious yet rare condition called lactic acidosis (a build up of lactic acid in the blood). Most often, lactic acidosis occurs in people with kidney problems, and it can be fatal.

Rosiglitazone may cause fluid retention, especially if it is used with insulin. Untreated fluid retention could lead to or worsen heart failure.

Avandamet should not be used with insulin, and should not be used by patients with kidney disease, congestive heart failure, or liver disease.

Mechanism of Action
Rosiglitazone maleate is a member of the thiazolidinedione class of antidiabetic agents and is a PPARgamma agonist. It improves glycemic control by improving insulin sensitivity while reducing circulating insulin levels.

Metformin hydrochloride is a member of the biguanide class of antidiabetic agents. It decreases hepatic glucose production, decreases intestinal absorption of glucose, and increases peripheral glucose uptake and utilization. Unlike sulfonylureas, metformin does not produce hypoglycemia in either patients with type 2 diabetes or normal subjects and does not cause hyperinsulinemia. With metformin therapy, insulin secretion remains unchanged, while fasting insulin levels and day-long plasma insulin response may actually decrease. (from FDA prescription label)