The FDA advisory panel recently voted to relax restrictions on the thioglitazones drug Avandia®. Avandia®, previously a big money maker for the pharmaceutical company, Glaxo-Smith Klein, has declined precipitously in usage to just a small percentage of people in recent years. In 2007 physicians cited evidence from several studies indicating that Avandia increased the risk of heart attack and cardiac death.
Following review of the evidence regarding Avandia® the FDA restricted its use to a last resort drug by those patients who had failed to see benefits from other forms of therapy.
Thioglitazones are known as insulin sensitizers. They work by sensitizing the body’s muscle and fat cells to the actions of insulin. Specifically they stimulate a receptor in the body that regulates the transcription of insulin responsive genes that work to transport and utilize glucose.
Avandia® is an effective drug which can lower A1C levels by approximately percent 1 to 2 percent, similar to the efficacy of the widely used drugs metformin and the sulfonyureas. Since it doesn’t have a direct effect on the pancreas, Avandia® has the advantage of not causing hypoglycemia, a side effect of many diabetes medications, including insulin. All drugs in the thioglitazones class can cause fluid retention and should be avoided in those prone to congestive heart failure. In addition, Avandia®, like all the thioglitazones, can promote weight gain which is a concern since many patients with type 2 diabetes are already overweight or obese.
The thioglitazones have had problems since they were first released. Rezulin® (troglitazone), the first drug released in the class in 1997, was taken off the market in 2000 due to concerns with its causing liver failure. Both of the thioglitazones currently on the market, pioglitazone (Actos®) and rosiglitazone (Avandia®), have black box warnings about the drugs propensity to cause heart failure. A black box warning (the information is literally surrounded by a heavy black lined box) is found on the label or prescribing information for pharmaceuticals. They’re used for two purposes: the drug has severe, deleterious effects in comparison to its benefits or there are special circumstances in which the drug should not be prescribed. For instance, a particular drug may work well in post-menopausal women but shouldn’t ever be used in women of child-bearing age.
In deciding to ease its restrictions of Avandia® the committee reevaluated the results of the 2009 Rosiglitazone Evaluated for Cardiovascular Outcomes and Regulation of Glycemia in Diabetes (RECORD) clinic trial sponsored by Glaxo Smith Klein. The committee decision does not exonerate Avandia®, but it gives physicians more latitude to use their clinical judgment when prescribing the drug. Om Ganda, MD, clinic physician at Joslin Diabetes Center believes the FDA’ prescribing modifications are well conceived. “The RECORD Trial did not show any increased incidence of cardiovascular disease in the rosiglitazone (Avandia) arm of the study.”