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Cardiovascular risks with thiazolidinediones in diabetes mellitus


A class of oral drugs used to treat type 2 diabetes mellitus may make heart failure worse, according to an editorial published in Heart.
Sonal Singh and Curt D Furberg recommend strong restrictions in the use of thiazolidinediones ( also known as glitazones ) and question the rationale for leaving Rosiglitazone on the market.
Rosiglitazone ( Avandia ) and Pioglitazone ( Actos ) are the two major thiazolidinediones.

In the editorial Singh and Furberg say that, at this time, justification for use of thiazolidinediones is very weak to non-existent.
Oral antidiabetics are given to control diabetes by lowering blood sugar. But diabetics also experience elevated rates of high blood pressure and high levels of cholesterol and triglyceride, which further compound their already increased risk of developing ischemic heart disease.
Heart disease and high blood pressure represent conditions that are major precursors of congestive heart failure.
About 22 percent of diabetics have heart disease. Among elderly patients with diabetes, more than half will develop congestive heart failure over a 10-year period.

The thiazolidinediones were approved for use based on the ability to reduce blood sugar. In contrast, the thiazolidinediones doubled the risk of congestive heart failure in patients with type 2 diabetes mellitus. The increased heart failure appears to be a class effect.

Singh and Furberg reported in The Journal of the American Medical Association in 2007 after an analysis of four long-term trials that use of Rosiglitazone was associated both with increased myocardial infarction and a doubling of heart failure.

The results from three large randomized clinical trials all failed to demonstrate that intensive control of blood sugar reduces mortality or events from cardiovascular disease in patients with type 2 diabetes.
The three trials were ACCORD, ADVANCE, and the Veterans Affairs Diabetes study.
In ACCORD, the patients who received intensive treatment to control blood sugar actually had more cardiovascular disease mortality than patients receiving standard treatment.
In ADVANCE, intensive control of blood sugar produced no benefit; there was no effect on cardiovascular events or deaths from cardiovascular causes compared to standard oral diabetes agents.
In the VA Diabetes trial, when intensive blood sugar control produced levels of blood sugar that were too low and led to loss of consciousness, that was a strong predictor of future cardiovascular events. ( Xagena )

Source: Wake Forest University Baptist Medical Center, 2008

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