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Home » Drug Information » FDA Approved Drugs » 1999
Medical Areas: Endocrinology

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Avandia (rosiglitazone maleate)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company: SmithKline Beecham
Approval Status: Approved June 1999
Treatment Area: Endocrinology

General Information

Avandia is indicated as monotherapy as an adjunct to diet and exercise to improve glycemic control in patients with type II diabetes mellitus. Avandia is also indicated for use in combination with metformin when diet, exercise, and Avandia alone or diet, exercise, and metformin alone do not result in adequate glycemic control in patients with type II diabetes. For patients inadequately controlled with a maximum dose of metformin, Avandia should be added to, rather than substituted for, metformin.

Avandia is an oral antidiabetic agent which acts primarily by increasing insulin sensitivity. Avandia is used in the management of type II diabetes mellitus (also known as non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes). Avandia improves glycemic control while reducing circulating insulin levels.

Clinical Results

A total of 2315 patients with type II diabetes, previously treated with diet alone or antidiabetic medication(s), were treated with Avandia as monotherapy in six double-blind studies, which included two 26-week placebo-controlled studies, one 52-week glyburide-controlled study, and three placebo-controlled dose-ranging studies of 8 to 12 weeks duration. Previous antidiabetic medication(s) were withdrawn and patients entered a 2 to 4 week placebo run-in period prior to randomization.

Two 26-week, double-blind, placebo-controlled trials, in patients with type 2 diabetes with inadequate glycemic control (mean baseline FPG approximately 228 mg/dL and mean baseline HbA1c 8.9%), were conducted. Treatment with Avandia produced statistically significant improvements in FPG and HbA1c compared to baseline and relative to placebo.

Side Effects

In clinical trials, approximately 4600 patients with type II diabetes have been treated with Avandia; 3300 patients were treated for 6 months or longer and 2000 patients were treated for 12 months or longer. The incidence and types of adverse events reported in clinical trials of Avandia were: upper respiratory tract infection, headache, back pain, hyperglycemia, fatigue, and sinusitis.

Mechanism of Action

Pharmacological studies in animal models indicate that rosiglitazone improves sensitivity to insulin in muscle and adipose tissue and inhibits hepatic gluconeogenesis. Rosiglitazone maleate is not chemically or functionally related to the sulfonylureas, the biguanides, or the alpha-glucosidase inhibitors.

Rosiglitazone, a member of the thiazolidinedione class of antidiabetic agents, improves glycemic control by improving insulin sensitivity. Rosiglitazone is a highly selective and potent agonist for the peroxisome proliferator-activated receptor-gamma (PPAR). In humans, PPAR receptors are found in key target tissues for insulin action such as adipose tissue, skeletal muscle, and liver. Activation of PPAR nuclear receptors regulates the transcription of insulin-responsive genes involved in the control of glucose production, transport, and utilization. In addition, PPAR-responsive genes also participate in the regulation of fatty acid metabolism.

Insulin resistance is a common feature characterizing the pathogenesis of type II diabetes. The antidiabetic activity of rosiglitazone has been demonstrated in animal models of type II diabetes in which hyperglycemia and/or impaired glucose tolerance is a consequence of insulin resistance in target tissues.

Rosiglitazone reduces blood glucose concentrations and reduces hyperinsulinemia in the ob/ob obese mouse, db/db diabetic mouse, and fa/fa fatty Zucker rat. Rosiglitazone also prevents the development of overt diabetes in both the db/db mouse and Zucker fa/fa Diabetic Fatty rat models.

In animal models, rosiglitazone’s antidiabetic activity was shown to be mediated by increased sensitivity to insulin’s action in the liver, muscle, and adipose tissues. The expression of the insulin-regulated glucose transporter GLUT-4 was increased in adipose tissue. Rosiglitazone did not induce hypoglycemia in animal models of type II diabetes and/or impaired glucose tolerance.

Additional Information

Patients should be informed of the following:

Management of type II diabetes should include diet control. Caloric restriction, weight loss, and exercise are essential for the proper treatment of the diabetic patient because they help improve insulin sensitivity. This is important not only in the primary treatment of type II diabetes, but in maintaining the efficacy of drug therapy.

It is important to adhere to dietary instructions and to regularly have blood glucose and glycosylated hemoglobin tested. Patients should be informed that blood will be drawn to check their liver function prior to the start of therapy and every two months for the first twelve months, and periodically thereafter.

Patients with unexplained symptoms of nausea, vomiting, abdominal pain, fatigue, anorexia, or dark urine should immediately report these symptoms to their physician.

Avandia can be taken with or without meals.