Pioglitazone demonstrates anti-atherosclerotic effect in type 2 diabetics

The thiazolidinedione pioglitazone has a beneficial effect on carotid intima media thickness (CIMT) compared with glimepiride in patients with type 2 diabetes, said Theodore Mazzone, MD, lead investigator of the CHICAGO (Carotid Intima Media Thickness in Atherosclerosis Using Pioglitazone) study.

CIMT, a surrogate marker for atherosclerosis and cardiovascular risk, was measured at baseline and again at 72 weeks in 462 patients with type 2 diabetes who were randomized to either 15 to 45 mg/d of pioglitazone or 1 to 4 mg/d of glimepiride. To be eligible, patients could not have symptomatic coronary artery disease, cerebrovascular disease, peripheral arterial disease, or cardiac failure at baseline.

Although both agents lowered blood glucose similarly, posterior wall CIMT increased by .012 mm in the patients randomized to the glimepiride group and decreased by .001 mm in those in the pioglitazone group (P =.017). The beneficial effect was observed across all subgroups based on age, gender, blood pressure, body mass index, glucose control, and duration of diabetes. Notably, about 60% of patients were on statin therapy, and the effect of pioglitazone on CIMT was apparent in these patients as well, said Dr. Mazzone, chief of endocrinology, diabetes, and metabolism at the University of Illinois at Chicago.

One patient taking pioglitazone was hospitalized for heart failure, which was reversed upon discontinuation of the drug. Although CHICAGO was not powered to detect differences in clinical events, 10 cardiovascular events occurred in the glimepiride group versus 4 in the pioglitazone group.

The finding is consistent with preclinical work with pioglitazone, which found this agent to have anti-inflammatory and anti-atherosclerotic effects, said Dr. Mazzone. "We have a solid foundation of experimental evidence showing that pioglitazone is beneficial for preventing atherosclerosis," he said.

Although changes in CIMT cannot be directly extrapolated to a change in clinical event rate, he noted that statins have demonstrated a similar benefit on CIMT that has translated into a reduction in clinical events.

"Pioglitazone could be part of a novel strategy to manage residual cardiovascular risk in type 2 diabetes," Dr. Mazzone said.