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
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
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antidiabetic medication(s) were withdrawn and patients entered a 2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.
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
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.
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.