Thiazolidinediones for Type 2 Diabetes

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Thiazolidinediones for Type 2 Diabetes


Generic NameBrand Name
pioglitazone and metforminActoplus Met
rosiglitazone and metforminAvandamet

Metformin is a biguanide medicine. For more information, see the Medications section of the topic Type 2 Diabetes: Recently Diagnosed.

How It Works

The action of these medicines in treating type 2 diabetes is not completely understood. They improve the way cells in the body respond to insulin by lowering insulin resistance. Unlike some other medicines used to treat diabetes, they do not cause the pancreas to produce more insulin.

Pioglitazone may help in the treatment of high cholesterol by reducing triglycerides and increasing high-density lipoproteins (HDL) in the blood. Rosiglitazone increases high-density lipoproteins (HDL) and slightly increases low-density lipoproteins (LDL).3 If you have high LDL, this may be a factor in selecting pioglitazone over rosiglitazone. The long-term effects of thiazolidinediones on cholesterol levels and the incidence of heart disease are not known.2

Unlike pioglitazone, rosiglitazone does not interact with certain medicines, such as the antibiotic erythromycin and birth control pills.

Why It Is Used

These medicines are not recommended as the first choice to lower blood sugar levels. Thiazolidinediones should be used only when other medicines have failed to lower blood sugar levels into a target range.

The U.S. Food and Drug Administration (FDA) recommends that rosiglitazone and pioglitazone be used alone or in combination with sulfonylurea medicines, metformin, or insulin shots.

How Well It Works

Clinical studies have shown that these medicines can effectively lower blood sugar levels.3

Side Effects

Some reported side effects of thiazolidinediones include:

  • Upper respiratory infections and sinusitis.
  • Headaches.
  • Mild anaemia.
  • Retention of fluid in the body. This may lead to heart failure.
  • Weight gain.
  • Muscle pain.

Women who take rosiglitazone (Avandia) or pioglitazone (Actos) may increase their risk for upper arm or foot fractures.

Troglitazone (Rezulin), a thiazolidinedione that has been removed from the market in the United States and some European countries, has been shown to cause severe liver problems in a small number of people who took it. The newer thiazolidinediones (rosiglitazone and pioglitazone) have not been shown to cause liver damage. But liver damage may still be a risk. Symptoms of liver damage include:

  • Nausea, vomiting, and belly pain.
  • Fatigue.
  • Loss of appetite.
  • Yellowing of the skin or the whites of the eyes (jaundice).
  • Dark urine.

If you are taking one of these medicines and have these symptoms, report them to your doctor immediately.

See Drug Reference for a full list of side effects. (Drug Reference is not available in all systems.)

What To Think About

Health Canada has announced a possible safety issue with the drug rosiglitazone (Avandia). Some studies have shown that people who take Avandia may raise their chance of having a heart attack. They may also raise their chance of death from heart disease.1

If you take Avandia, do not stop taking the medicine. Call your doctor to talk about which medicine is best for you.

People who have heart failure or are at risk for it should not use these medicines. Talk to your doctor about whether you should take these medicines. Call your doctor immediately if you notice a sudden increase in your weight or experience shortness of breath or other symptoms of heart failure.

People with liver disease should not take thiazolidinediones. Children also should not take these medicines because of the risk of developing liver problems. If you are taking rosiglitazone or pioglitazone, you need to have blood tests before starting the medicine, then every 2 months during the first year, and periodically thereafter to make sure your liver is not being damaged. If blood test results show liver damage, you will have to stop taking the medicine.

Talk with your doctor if you want to become pregnant or are pregnant and are taking one of these medicines. You may be given another medicine, because the use of these medicines during pregnancy has not been studied.

Women who have stopped menstruating before they start taking these medicines may begin menstruating again and may become pregnant.

If you are taking this medicine along with insulin or a sulfonylurea, which causes the pancreas to produce more insulin, you may need to take a lower dose of the insulin or sulfonylurea to prevent low blood sugar (hypoglycemia).

Complete the new medication information form (PDF) (What is a PDF document?) to help you understand this medication.



  1. Kaul S, et al. (2010) Thiazolidinedione drugs and cardiovascular risks: A science advisory from the American Heart Association and American College of Cardiology Foundation. Circulation, 121(16): 1868–1877.
  2. Canadian Diabetes Association (2008). Clinical practice guidelines for the prevention and management of diabetes in Canada. Available online:
  3. Lebowitz HE (2005). Management of hyperglycemia with oral antihyperglycemic agents in type 2 diabetes. In CR Kahn et al., eds., Joslin's Diabetes Mellitus, 14th ed., pp. 687–710. Philadelphia: Lippincott Williams and Wilkins.


By Healthwise Staff
Primary Medical Reviewer E. Gregory Thompson, MD - Internal Medicine
Primary Medical Reviewer Brian D. O'Brien, MD - Internal Medicine
Specialist Medical Reviewer Matthew I. Kim, MD - Endocrinology
Last Revised August 4, 2010

This information does not replace the advice of a doctor. Healthwise, Incorporated disclaims any warranty or liability for your use of this information.