Nissen SE et al. (2008) Comparison of pioglitazone vs glimepiride on progression of coronary atherosclerosis in patients with type 2 diabetes: the PERISCOPE randomized controlled trial. JAMA 299: 1561–1573

People with type 2 diabetes are particularly susceptible to coronary artery disease; however, whether glucose-lowering medications affect the progression of atherosclerosis in such individuals is uncertain. Results of the recent PERISCOPE trial suggest that the thiazolidinedione compound pioglitazone, which increases the sensitivity of peripheral tissues to insulin, slows the progression of atherosclerosis.

Nissen et al. assessed 543 patients with type 2 diabetes and coronary artery disease who were randomly assigned to receive either pioglitazone or glimeparide, an insulin secretagogue. Participants underwent coronary intravascular ultrasonography examination at baseline and after 18 months of treatment.

Mean atheroma volume increased by 0.73% (95% CI 0.33%–1.12%) in the glimeparide group, whereas volume decreased by 0.16% (95% CI −0.57% to 0.25%) in the pioglitazone group (P = 0.002). Pioglitazone also had more-favorable effects on HbA1c, fasting blood glucose, HDL cholesterol, triglyceride and C-reactive protein levels than did glimeparide, but was associated with greater mean weight gain. The incidence of major cardiovascular events was similar in the two treatment groups. Glimeparide was associated with higher incidences of angina and hypoglycemia, whereas pioglitazone was associated with higher incidences of peripheral edema and fracture.

The mechanism by which pioglitazone inhibits atherogenesis remains to be determined; however, the favorable effects on atherosclerosis-related biomarkers observed for pioglitazone have not been seen with other thiazolidinediones.