Which medications in the drug class Thiazolidinediones are used in the treatment of Glucose Intolerance?

Updated: Jul 08, 2020
  • Author: Samuel T Olatunbosun, MD, FACP, FACE; Chief Editor: George T Griffing, MD  more...
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These agents stimulate peripheral use of glucose as stimulated by insulin. Rosiglitazone and pioglitazone are commonly used.

Following the online publication of a meta-analysis, the Food and Drug Administration on May 21, 2007, issued an alert to patients and health care professionals stating that rosiglitazone can potentially cause an increased risk of myocardial infarction and heart-related deaths. Rosiglitazone is an antidiabetic agent (thiazolidinedione derivative) that improves glycemic control by improving insulin sensitivity.

The drug is highly selective and is a potent agonist for peroxisome proliferator-activated receptor gamma (PPAR gamma). Activation of PPAR-gamma receptors regulates insulin-responsive gene transcription involved in glucose production, transport, and utilization, thereby reducing blood glucose concentrations and reducing hyperinsulinemia. Potent PPAR-gamma agonists have been shown to increase the incidence of edema. A large scale phase III trial (RECORD) is underway that is specifically designed to study cardiovascular outcomes of rosiglitazone.

As of September 2010, the FDA is requiring a restricted access program to be developed for rosiglitazone under a risk evaluation and mitigation strategy (REMS). Patients currently taking rosiglitazone and benefiting from the drug will be able to continue if they choose to do so. Rosiglitazone will only be available to new patients if they are unable to achieve glucose control on other medications and are unable to take pioglitazone, the only other thiazolidinedione.

For more information, see FDA’s Safety Alert on Avandia. The meta-analysis published online, entitled "Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes" can be viewed at The New England Journal of Medicine. Additionally, responses to the controversy can be viewed at the Heartwire news (theheart.org from WebMD), including the following articles: Rosiglitazone increases MI and CV death in meta-analysis and The rosiglitazone aftermath: legitimate concerns or hype?

Rosiglitazone (Avandia)

Available only through a restricted access program. Rosiglitazone sensitizes target cells' response to insulin and has an effect on the stimulation of glucose uptake in skeletal muscle and adipose tissue.

Pioglitazone (Actos)

Pioglitazone improves target cell response to insulin and increases insulin-dependent glucose use in skeletal muscle and adipose tissue.

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