Pioglitazone may slow progression of atherosclerosis in patients with diabetes as well as improve sensitivity to insulin, according to a presentation at the annual meeting of the American Heart Association. It will be published in the December 6 print issue of JAMA
Theodore Mazzone, MD, of the University of Illinois at Chicago College of Medicine, and colleagues studied possible anti-atherosclerosis effects of pioglitazone in 462 adults with type 2 diabetes in the Chicago metropolitan area between 2003 and 2006.

Study participants (average age, 60 years; 289 men, 173 women) were randomized to receive a daily dose of pioglitazone (15 to 45 milligrams) or glimepiride (1 to 4 milligrams), a diabetes medication that works through different mechanisms. At the beginning of the study and 24, 48, and 72 weeks later, ultrasound was used to measure carotid artery intima-media thickness. Glycosylated hemoglobin (HbA1c) levels, as well as blood pressure, blood cholesterol, and adverse events were also monitored throughout the study.

A total of 158 (68 percent) of the pioglitazone group and 165 (72 percent) of the glimepiride group completed the 72-week trial; 175 (76 percent) of the pioglitazone group and 186 (81 percent) of the glimepiride group had at least one ultrasound of the carotid artery and were included in the artery wall thickness analysis.

At baseline, average wall thickness was comparable between groups (0.771 millimeters vs. 0.779 millimeters). At the 72-week follow-up, wall thickness of patients in the glimepiride group increased by an average of 0.012 millimeters from baseline, whereas the average wall thickness in the pioglitazone group decreased by 0.001 millimeters.

"A pre-specified subgroup analysis based on age, sex, systolic blood pressure, duration of type 2 diabetes mellitus, body mass index, HbA1c value and statin use showed a uniform beneficial effect of pioglitazone treatment," the authors wrote.

Over the course of the study, blood pressure changes were not significantly different between groups. HbA1c levels were similar until week 48, when levels in the pioglitazone group became significantly lower than in the glimepiride group.

High-density lipoprotein cholesterol levels increased in the pioglitazone group by week 24 and remained higher through 72 weeks compared with levels in the glimepiride group, representing a potential mechanism by which pioglitazone reduced artery thickness, according to the authors. Another possible mechanism is a direct drug effect on the artery wall.

"Additional data will be needed to determine the clinical significance of these findings; specifically, whether a strategy of routine use of pioglitazone instead of glimepiride substantially reduces major cardiovascular events," the group concluded.