Which medications in the drug class Antidiabetic Agents, Thiazolidinediones are used in the treatment of Insulin Resistance?

Updated: Aug 07, 2019
  • Author: Samuel T Olatunbosun, MD, FACP, FACE; Chief Editor: George T Griffing, MD  more...
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Antidiabetic Agents, Thiazolidinediones

Thiazolidinediones are insulin-sensitizing drugs that increase the disposal of glucose in peripheral tissues and act by activating a specific nuclear receptor, the peroxisome proliferator-activated receptor gamma (PPAR-gamma). Thiazolidinediones have a major effect in the stimulation of glucose uptake, skeletal muscle, and adipose tissue. They lower plasma insulin levels and are used to treat type 2 diabetes associated with insulin resistance. They appear to benefit patients with PCOS. Thiazolidinediones include rosiglitazone and pioglitazone. [9, 68]

Pioglitazone (Actos)

Pioglitazone may be used in monotherapy and in combination with metformin, insulin, or sulfonylureas. It improves target cell response to insulin without increasing insulin secretion from pancreas. It decreases hepatic glucose output and increases insulin-dependent glucose use in skeletal muscle and, possibly, in liver and adipose tissue.

Rosiglitazone (Avandia)

Rosiglitazone is an insulin sensitizer with a major effect in stimulating glucose uptake in skeletal muscle and adipose tissue. It lowers plasma insulin levels. Rosiglitazone is used for treatment of type 2 diabetes associated with insulin resistance and may benefit polycystic ovary syndrome (PCOS) patients. It may be used as monotherapy or in combination with metformin.

Rosiglitazone is highly selective and a potent agonist for PPAR-gamma. The activation of PPAR-gamma receptors regulates insulin-responsive gene transcription involved in glucose production, transport, and utilization, thereby lowering 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 currently underway that is specifically designed to study cardiovascular outcomes of rosiglitazone.

On May 21, 2007, following the online publication of a meta-analysis, the US Food and Drug Administration (FDA) issued an alert to patients and health care professionals warning that rosiglitazone can potentially increase the risk for myocardial infarction and heart-related deaths.

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, entitled Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes, can be viewed online. Additionally, responses to the controversy—including the articles Rosiglitazone increases MI and CV death in meta-analysis and The rosiglitazone aftermath: legitimate concerns or hype? —can be viewed at the Heartwire news site (the heart.org), from WebMD.

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