General Information

Avandia (rosiglitazone maleate) is an oral antidiabetic agent that acts primarily by increasing insulin sensitivity.

Avandia is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. 

Avandia is supplied as tablets for oral administration. Start at 4 mg daily in single or divided doses; do not exceed 8 mg daily. Dose increases should be accompanied by careful monitoring for adverse events related to fluid retention. Do not initiate Avandia if the patient exhibits clinical evidence of active liver disease or increased serum transaminase levels. 

Mechanism of Action

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 2 diabetes. The antidiabetic activity of rosiglitazone has been demonstrated in animal models of type 2 diabetes in which hyperglycemia and/or impaired glucose tolerance is a consequence of insulin resistance in target tissues.

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 2 diabetes and/or impaired glucose tolerance.

Side Effects

Adverse effects associated with the use of Avandia may include, but are not limited to, the following:

• Upper respiratory tract infection
• Headache
• Back pain
• Hyperglycemia
• Fatigue
• Sinusitis

The Avandia drug label comes with the following Black Box Warning: Thiazolidinediones, including rosiglitazone, cause or exacerbate congestive heart failure in some patients. After initiation of Avandia, and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain; dyspnea; and/or edema). If these signs and symptoms develop, the heart failure should be managed according to current standards of care. Furthermore, discontinuation or dose reduction of Avandia must be considered. Avandia is not recommended in patients with symptomatic heart failure. Initiation of Avandia in patients with established NYHA Class III or IV heart failure is contraindicated

Clinical Trial Results

A total of 2,315 patients with type 2 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 eight to 12 weeks. Previous antidiabetic medication(s) were withdrawn and patients entered a two- to four-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 fasting plasma glucose level of approximately 228 mg/dL and mean baseline hemoglobin A1c 8.9%) were conducted. Treatment with Avandia produced statistically significant improvements in glucose and hemoglobin compared to baseline and relative to placebo.