What is Rosiglitazone?

Rosiglitazone is an anti-diabetic drug that in the chemical class of thiazolidinediones. This compound is effective at restoring cells' ability to respond to insulin for people with Type II diabetes. The drug can be taken alone, often sold under the name Avandia®, or can be taken in combination with metformin or sulfonylureas. Rosiglitazone has been the subject of controversy, since there is evidence that it can lead to heart attacks. A panel of the United States Food and Drug Administration (FDA) considered whether to take the drug off the market in 2010, but decided it was valuable enough to allow it to be continued to be sold under tight restrictions.

There are two anti-diabetic drugs in the thiazolidinedione class. In addition to rosiglitazone, there is pioglitazone, also known as Actos®. The mode of action for drugs in this class is to make cells more sensitive to insulin. This results in a reduction in the concentration of sugar, insulin, and fatty acids in the blood.

These drugs cause these changes by activating receptors on the membranes of the cell's nucleus. The nucleus is the location of the cell where most of the DNA is stored. Receptors are molecular switches that signal events to happen when a particular compound binds to them.

Peroxisomes are cellular structures in which much of the body's fatty acid metabolism takes place. In this case, rosiglitazone binds to a particular subtype of receptor called a peroxisome proliferator-activated receptor (PPAR), of which there are many different types. The binding of this drug to a particular PPAR activates it to express DNA that regulates genes involved in fat cell development, fatty acid metabolism, and the uptake of blood sugar.

These changes take effect in fat, muscle, and liver tissues. With a decreased sensitivity to insulin, these tissues function more effectively. These changes help to control Type II diabetes. The thiazolidinediones are meant to be used in conjunction with lifestyle changes, such as modifying one’s diet and getting more exercise.

As rosiglitazone became a commonly used drug, studies appeared linking the drug to an increased frequency of heart attacks. A number of lawsuits were placed against the manufacturer, although many were settled. In 2010, the FDA held several meetings to consider putting restrictions on the drug, first putting a black box warning on the drug's packaging warning of potential heart problems. In September 2010, the FDA and European drug regulators decided that the drug could no longer be sold in Europe, and that sales in the US would be limited only to patients who have had no success using other medicines.