Thiazolidinediones: Oral Medication for Type 2 Diabetes

Man injecting himself with Insulin pen injector. Credit: BSIP/UIG / Getty Images

What Are Thiazolidinediones?

Thiazolidinediones are oral medications that help lower blood sugar in type 2 diabetes. In addition to a healthy diet and exercise, they are another way to control blood sugar levels. They are also known as glitazones.

Thiazolidinediones currently available in the United States include Actos (pioglitazone), Avandia (rosiglitazone) and a combination drug, Avandamet (rosiglitazone and metformin).

The FDA lifted prescription restrictions on rosiglitizone in 2013 after concluding new evidence showed no increased risk of heart attack, but bans remain in place in Europe.

What Thiazolidinediones Do

Thiazolidinediones help to lower insulin resistance in cells, improving the way that the body responds to insulin. Thiazolidinediones are typically taken by mouth once or twice daily. They may be used alone, with other pills or with insulin.

What Thiazolidinediones Do Not Do

Thiazolidinediones do not replace insulin in the body, nor do they prompt the body to create additional insulin. They are not meant to replace the healthy diet a doctor recommends.

History of Thiazolidinedione Use - Restrictions Added and then Removed by FDA

Thiazolidinediones have been used to treat type 2 diabetes since the late 1990s. The first drug in this class, Rezulin, was removed from the U.S. market because of rare but serious liver problems.

Some reports have raised concerns about an increased risk of heart failure in patients taking Avandia. Other reports have suggested an increased risk of heart attack with thiazolidinediones, although this link remains unproven.

The Food and Drug Administration ordered in 2006 that drug labels for Avandia warn of increased risk of heart attacks and chest pain in some patients.

Use of Avandia dropped significantly after the first warnings were issued. In 2010 the FDA restricted new prescriptions for Avandia to only people who were not able to control their blood glucose with other diabetes medications or were unable to take Actos. 

In 2013, the results of the RECORD clinical trial found no increased risk of heart attack with Avandia (rosiglitazone). As a result, in 2013 the FDA lifted the prescribing restrictions it placed on Avandia. On Dec. 16, 2015, the FDA eliminated the Risk Evaluation and Mitigation Strategy for rosiglitazone-containing medications, concluding that the benefits outweigh the risks.

However, the European Medicines Agency suspended sales of rosiglitazone in 2010 and the French and German Medicines Agencies also suspended use of pioglitazone (Actos) in 2011.

Who Should Not Use Thiazolidinediones

People with type 1 diabetes (requiring regular insulin injections), heart failure or liver disease should not use thiazolidinediones. Children and pregnant or nursing women should also avoid using these medications.

People with eye or bone problems should talk with their health care providers before taking thiazolidinediones.

What Are the Side Effects and Risks?

Common side effects include weight gain, upper respiratory infections, sinus infections, headaches and mild anemia. Serious side effects include fluid retention, heart failure, weight gain and muscle pain. Other side effects may include headaches, high cholesterol, weakened bones, eye problems and hives.

While there is no current evidence indicating that Actos or Avandia cause liver problems, it’s wise to keep an eye out for such symptoms as nausea, vomiting, abdominal pain, fatigue, loss of appetite, jaundice (yellowing of the skin and eyes) and dark urine.

Other “Off-Label” Uses of Thiazolidinediones

Actos may help in treating high cholesterol. Thiazolidinediones may also help to increase ovulation and fertility in polycystic ovary syndrome.

What Else Should I Know About Thiazolidinediones?

Thiazolidinediones should be taken every day. They may take up to three months to take full effect. If one experiences any side effects, particularly swelling, sudden weight gain, difficulty breathing, heart palpitations, menstrual changes or broken bones, notify a health care provider immediately.

People with diabetes, however, should not stop taking their medication unless instructed to do so. It is important to see a doctor for close follow-up care while taking thiazolidinediones. This should include blood sugar testing, liver function tests and eye testing.


Mahaffey, Kenneth W.; Hafley, Gail; Dickerson, Sheila; Burns, Shana; Tourt-Uhlig, Sandra; White, Jennifer; Newby, L. Kristin; Komajda, Michel; McMurray, John; Bigelow, Robert; Home, Philip D.; Lopes, Renato D. (2013). "Results of a reevaluation of cardiovascular outcomes in the RECORD trial". American Heart Journal 166 (2): 240–249.e1.

Drazen, M.D., Jeffrey M., Stephen Morrissey, Ph.D., and Gregory D. Curfman, M.D.. "Rosiglitazone — Continued Uncertainty about Safety." The New England Journal of Medicine. 357(2007): 63-64.

FDA Drug Safety Communication: FDA requires removal of some prescribing and dispensing restrictions for rosiglitazone-containing diabetes medicines. FDA Newsroom. 11/25/2013. U.S. Food and Drug Administration.

David K. McCulloch, MD. "Thiazolidinediones in the treatment of diabetes mellitus," Dec. 17, 2015. UpToDate.

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