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Diabetes Drug Reduces Cardiovascular Risks

Nov 21, 2006

A drug commonly used to increase the body’s sensitivity to insulin may slow the progression of cardiovascular disease in patients with type 2 diabetes, according to a study at the University of Illinois at Chicago College of Medicine. The study, led by Dr. Theodore Mazzone, professor of medicine at UIC, found that patients with type 2 diabetes are known to have an increased risk of heart attack and other cardiovascular events. Some evidence suggests that a class of oral drugs used to treat type 2 diabetes called thiazolidinediones may be useful in reducing the progression of atherosclerosis, a thickening and hardening of the arteries that can lead to cardiac events.

Mazzone and colleagues conducted a Chicago-area multicenter trial to test a potential new approach for slowing the thickening of artery walls in diabetic patients.


They enrolled 462 racially and ethnically diverse adults with type 2 diabetes. The 289 men and 173 women, whose average age was 60, were randomly assigned to receive either pioglitazone (a thiazolidinedione sold as Actos), a drug that increases the body’s sensitivity to insulin, or glimepiride (sold as Amaryl), another type of diabetes drug that stimulates the pancreas to make more insulin.

Patients received a baseline ultrasound to measure the thickness of the lining and middle layers of the carotid arteries, which carry blood to the brain. The arteries’ thickness is a marker for coronary atherosclerosis and a predictor of future heart attack. The patients were then evaluated at 24, 48 and 72 weeks to measure the progression of thickenening.

"The less the thickening, and the slower the rate of thickening, the less risk of heart attack in general," said Mazzone.

By the end of the study, patients taking pioglitazone had an artery thickness that decreased an average of 0.001 millimeters, while in those taking glimepiride it increased 0.012 millimeters. About 70 percent of all patients were able to complete the 72-week trial.

The study, Mazzone said, showed that pioglitazone significantly slowed the thickening of the carotid artery wall compared to the other diabetes drug.

"We showed this for both the average thickness of the wall, as well as the maximum thickness of the wall," he said.

The beneficial effect of pioglitazone was uniform regardless of age, sex, duration of diabetes, blood pressure, blood cholesterol levels or blood glucose control.

Among the findings:

· In the Actos group hemoglobin A1C (HbA1C) values decreased by week 16 and remained steady, versus a rapid decrease in the Amaryl group followed by a gradual increase that continued until week 72.
· HDL increased with Actos compared to Amaryl.
· Triglycerides decreased by 13.5% in the Actos group and increased by 2.1% in the Amaryl group (P<0.0010).
· LDL increased by 5.8% in the Actos group and 1% in Amaryl group (NS).

The slowing of CIMT progression was observed in all Actos treated patients, regardless of age, gender, obesity, hypertension, duration of diabetes, or glucose control, he said.

Moreover the benefit was observed irrespective of whether the patient was using a statin, Dr. Mazzone said.

The study also monitored cardiovascular clinical events. There were four adverse events in the pioglitazone treated group, including three patients who required coronary revascularization. There were 10 adverse events in the glimepiride treated group, including eight who required coronary revascularization.

"Additional data needs to be brought to bear," said Mazzone, "however this is very helpful for suggesting that pioglitazone could be a useful, novel approach for managing cardiovascular risk in patients with diabetes."

The study was funded by Takeda. Aguilar D, Deswal A. Thiazolidinediones are not associated with increased risk of heart failure hospitalizations in ambulatory patients with diabetes mellitus and heart failure. American Heart Association 2006 Scientific Sessions; November 12-15, 2006; Chicago, IL. Abstract 1894.


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