A thiazolidinedione agent.

An agonist of peroxisome proliferator activated receptors (PPARs), primarily gamma receptors, in the cell nucleus.

Peroxidase proliferator activated receptor gamma (PPARΥ), a nuclear receptor and transcription factor that regulates the expression of hundreds of genes and adipocyte differentiation.

Increases hepatic and peripheral insulin sensitivity, and reverses insulin resistance.

Initially approved because of reports of decreased insulin resistance, blood pressure, microalbuminuria, and improvement in cardiovascular surrogate markers of CRP and carotid intimal thickness.

Reports of risks of heart failure, vision loss from macular edema, fractures in women and myocardial infarction.

No evidence that this drug’s glycemic control leads to reduction in macrovascular complications of type 2 diabetes.

In a meta-analysis of 42 studies (Nissen and Wolski) comparing this agent with other therapies or placebo for type 2 diabetes resulted in a significant increased in the risk of myocardial infarction with an odds ratio of 1.43 and a borderline significant finding for death from cardiovascular causes with an odds ratio of 1.64.

The meta-analysis comparing this agent to placebo revealed an odds ratio for myocardial infarction of 1.8 and the odds ratio for death from cardiovascular disease at 1.22.

Analysis of 42 trials found an increased risk of myocardial infarction and cardiovascular death.

The meta-analysis study has significant weaknesses and because the number of events was small the findings due to chance cannot be excluded.

Avandia Associated with a 43% increase of myocardial infarction, so that the American Diabetes Association recommends against the use of the drug for managing hyperglycemia.

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