Pioglitazone appears to be the first diabetes therapy able to reduce progression of coronary atherosclerosis in patients with type 2 diabetes, according to a late-breaking clinical trial presented at the meeting of the American College of Cardiology.

The PERISCOPE trial (Pioglitazone Effect on Regression of Intravascular Sonographic Coronary Obstruction Prospective Evaluation) compared two approaches to management of diabetes, randomizing 543 patients for 18 months to the thiazolidinedione pioglitazone, which reduces blood glucose level by increasing insulin sensitivity or the sulfonylurea glimepiride, which lowers blood glucose by stimulating insulin release by the pancreas).

The prospective, randomized, multicenter, double-blind trial treated patients with coronary disease and type 2 diabetes for 18 months at 97 academic and community hospitals in North and South America. Patients underwent intravascular ultrasonography to measure the amount of plaque volume at entry. Patients received either glimepiride, 1-to-4 mg, or pioglitazone, 15-to-45 mg, titrated to maximum dosage, if tolerated. After 18 months, a second ultrasound examination was performed to determine the amount of change in coronary plaque volume. The primary endpoint was the rate of progression of coronary plaque as measured by the ultrasound procedure.

The principal finding was an absence of progression of coronary plaque with pioglitazone (negative 0.16 percent) compared with highly significant progression with glimepiride (positive 0.73 percent) as assessed with intravascular ultrasound.

There were also major differences between treatments in biochemical effects including marked differences in levels of high-density lipoprotein cholesterol, triglycerides and C-reactive protein. Other important endpoints included changes in glycohemoglobin levels, insulin levels, other lipid parameters and blood pressure - all more favorable for patients treated with pioglitazone.

There were adverse effects in both treatment groups: More patients assigned to glimepiride experienced episodes of low blood sugar or angina and more patients assigned to pioglitazone experienced edema and fractures.

"Atherosclerosis can be particularly aggressive in patients with diabetes, which is currently increasing at an alarming rate in the developed and developing world," said Steven Nissen, MD, Chairman, Department of Cardiovascular Medicine, Cleveland Clinic and lead author. "By defining the optimal strategy for managing coronary heart disease in this patient population, this study has major implications for how we will treat diabetics with coronary disease in the future."