Thiazolidinediones (TZDs)

Actos (pioglitazone) and Avandia (rosiglitazone) are the two thiazolidinedione (TZD) drugs currently available in the United States. A third drug in the class, Rezulin (troglitazone), was withdrawn from the market in 2000 after reports of fatalities due to liver damage.

The Food and Drug Administration (FDA) has approved Actos for use with insulin, metformin, or sulfonylureas. Avandia is cleared for use with metformin or sulfonylureas. Actos is usually taken once daily, and Avandia may be taken once or twice daily. Both can be taken with or without food.

How They Work

The TZD drugs, which are also called glitazones or insulin sensitizers, target the insulin receptors in muscle and fat cells to increase the level of insulin sensitivity in the body. They reduce glucose production by the liver (to a small extent), and are also effective in controlling blood pressure. Some TZDs also may be helpful in lowering triglyceride levels and in increasing HDL (or “good”) cholesterol.

Possible Side Effects

In 2007, a study was published that pointed to an increased cardiovascular mortality risk for patients taking Avandia. Specifically, the drug has been associated with an increased risk of heart attack and angina, and now carries an FDA-mandated “black box warning” to this effect.

A long-term study known as Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) is scheduled to be completed in the summer of 2008, and should hold some answers to the cardiovascular safety of Avandia. You should talk to your doctor about your overall risk of cardiovascular problems and whether or not Avandia is right for you.

Fact

If you take birth control pills, TZD drugs can make them less effective. They can also increase fertility in women with polycystic ovary disease (PCOS). Women who take TZD drugs should speak with their doctor about contraceptive options.

TZD drugs have also been linked to congestive heart failure (CHF), and they are known to make pre-existing CHF worse. Patients with CHF should not take any TZD drug. If your doctor starts you on a TZD, or increases your dose, you and your doctor should watch carefully for signs of edema (swelling), sudden rapid weight gain, and dyspnea (severe shortness of breath) — all symptoms of heart failure.

Because of the associations found between Rezulin and liver failure, the FDA has imposed strict guidelines on assessing liver function in patients taking other TZD drugs. If you take a TZD, you must have regular testing of the liver enzyme ALT. ALT levels should be tested before treatment starts, every two months for the first year you take the drug, and as recommended by your doctor thereafter. Avandia or Actos should be discontinued if ALT levels rise more than three times the normal upper limit, and should not be started in patients who have ALT levels that are greater than 2.5 times higher than the normal upper limit.

Other side effects of TZD therapy may include the following:

  • Anemia

  • Weight gain

  • Muscle weakness

  • Headaches

  • Fatigue

  • Cold-like symptoms

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