Avandia for Diabetes

Avandia is an anti-diabetic drug marketed by GlaxoSmithKline. It is also sold as a combination drug with metformin, called Avandamet, and with glimeride, called Avandaryl. The patent for this drug expires in 2012. Avandia, generically known as rosiglitazone, is classified as a thiazolidinedione, or TZD. This class of drugs is used to treat type 2 diabetes, but not type 1 diabetes.

Mechanism of Action

A review of TZDs in the Journal of Clinical Investigation reported clinical studies have demonstrated that TZDs decrease serum glucose and insulin levels, increase cellular glucose uptake and also reduce triglyceride levels. TZDs increase the sensitivity of cells to insulin, thereby restoring insulin sensitivity in insulin-resistant diabetics. Many of the effects of TZDs are the result of activation of a certain receptor protein, known as PPAR gamma, which regulates the expression of genes involved in glucose and lipid metabolism and energy homeostasis.

Glycemic Control

The clinical goal of diabetes treatment is to reduce hyperglycemia and not increase the frequency of hypoglycemic episodes. As reported in the journal Current Opinion in Lipidology in 2007, two clinical trials with rosiglitazone demonstrated it was more effective than metformin and glyburide in restoring glycemic control in newly diagnosed diabetics and decreased the progression to diabetes in prediabetics by 60 percent. The American Diabetes Association treatment algorithm for type 2 diabetes recommends initial therapy begin with metformin; if the glycemic target is not met, a TZD, sulfonylurea or insulin may be added to the treatment regimen.

Hypoglycemia

The National Library of Medicine reports that the incidence of hypoglycemia associated with Avandia treatment alone or in combination with other anti-diabetic drugs is less than 1 percent. However, when Avandia is used in combination with insulin, the incidence of hypoglycemia rose from 6 percent for insulin alone to between 12 and 14 percent for insulin in combination with Avandia.

Side Effects

The Food and Drug Administration’s official label for Avandia reports that the adverse events occurring in greater than 5 percent of persons treated with Avandia were upper respiratory tract infections, injury and headache. The causality of these events was not reported. Additionally, some studies reported a greater incidence of anemia, edema, and bone fractures in patients treated with Avandia. The incidence of myocardial ischemic events in patients treated with Avandia was 2 percent versus 1.5 percent in those who were not treated with Avandia.

FDA Warning

The FDA has required that thiazolidinedione drugs have a warning label that states that these drugs cause or exacerbate congestive heart failure in some patients. The FDA further recommends that patients with heart failure symptoms do not take Avandia. The FDA reviewed greater than 45 clinical studies with Avandia and stated “the available data on the risk of myocardial ischemia are inconclusive.” Avandia remains an FDA-approved drug for the treatment of diabetes as of July 2010. A more recent review of the evidence published in The Annals of Pharmacotherapy concludes “rosiglitazone, but not pioglitazone, is associated with an increased risk of myocardial ischemic events, although the absolute magnitude is extremely small.” On June 28, 2010 the American Diabetes Association reported that a multicenter trial on thousands of diabetic patients with established heart disease found no evidence that treatment with rosiglitazone causes an increased risk for stroke or heart attacks.