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Slowing Progression of Atherosclerosis in Diabetic Patients

Pioglitazone outperformed glimepiride in a preliminary trial.

Cardiovascular disease is responsible for 75% of deaths in patients with diabetes, but whether blood sugar control itself lowers this risk is unclear. Researchers addressed that issue in what is purportedly the first head-to-head comparison of a sulfonylurea (an insulin secretagogue) and a thiazolidinedione (an insulin sensitizer); 543 diabetic adults (age range, 35–85) with known coronary artery disease and glycosylated hemoglobin (HbA_1c) levels <10% were randomized to daily therapy with the sulfonylurea glimepiride or the thiazolidinedione pioglitazone (Actos). The maker of pioglitazone funded the multicenter study, and its employees were on the research team.

Most patients were taking standard preventive therapies (e.g., aspirin, statins), and patients were permitted to continue other diabetes drugs, such as metformin or insulin. HbA_1c levels were roughly 7% for both groups during treatment. Intravascular ultrasound assessment of atherosclerosis was available for 360 subjects (66%) after 18 months of treatment and showed that atheroma volume increased in the glimepiride group and decreased in the pioglitazone group (least square mean change, 0.73% vs. –0.16%; P=0.002). An analysis that included noncompleters showed a similar difference. Hypoglycemia was more common with glimepiride, and edema and fractures were more common with pioglitazone.

Comment: These results suggest that an insulin sensitizer is superior to an insulin secretagogue in lowering risk for heart disease in diabetic patients; however, this trial is limited by the high rate of noncompletion and the researchers’ failure to access actual clinical endpoints. The results certainly justify a larger clinical trial to address these limitations but do not support a change in clinical decision making. Note that in the previously published PROactive trial (Journal Watch Nov 8 2005), pioglitazone was associated with a small decrease in vascular events and a small increase in congestive heart failure among patients who were receiving other antidiabetic therapies.

— Thomas L. Schwenk, MD

Published in Journal Watch General Medicine April 1, 2008

Citation(s):

Nissen SE et al. Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: The PERISCOPE randomized controlled trial. JAMA 2008 Apr 2; 299:1561.

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