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Pioglitazone But Not Glimepiride Slows Progression of Carotid Intima-Media Thickness in Patients with Type 2 Diabetes: Presented at AHA

By W. A. Thomasson, PhD

CHICAGO, IL -- November 14, 2006 -- Patients with type 2 diabetes who are treated with pioglitazone experience less atherosclerotic thickening of the intimal and medial layers of their carotid arteries than do those who are treated with glimepiride, according to a study presented here at the 2006 Scientific Sessions of the American Heart Association (AHA).

The study, published simultaneously online in the Journal of the American Medical Association, was presented by Theodore Mazzone, MD, professor of medicine and pharmacology, University of Illinois, Chicago, Illinois. Carotid intima-media thickening (CIMT) is considered a general indicator of cardiovascular as well as cerebrovascular risk.

Study participants were 462 men and women aged 45 to 85 years with type 2 diabetes mellitus. Subjects with symptomatic cardiovascular, cerebrovascular, or peripheral vascular disease at baseline were excluded. Participants were randomized to treatment with either pioglitazone or glimepiride and followed for 72 weeks, with CIMT thickness being measured at 24-week intervals.

At baseline, participants' blood pressure was well controlled and their low-density lipoprotein (LDL) cholesterol and glycated hemoglobin (HbA1c) levels reasonably well controlled.

In the glimepiride group, average CIMT rose slowly between baseline and week 72. In the pioglitazone group, by contrast, average CIMT fell between baseline and week 24, remained essentially constant between weeks 24 and 48, and then returned to near baseline by week 72.

There was a statistically significant difference between the 2 groups at weeks 48 and 72 (P =.017 at week 72). Similar results were seen when CIMT was expressed in terms of maximal rather than average thickness. Analysis by subgroups based on age, body mass index, hemoglobin A1c (HbA1c) level, and use of statins showed an advantage for pioglitazone in all groups, although many differences were not statistically significant.

Levels of HbA1c decreased rapidly in the glimepiride group but returned to baseline by week 72. The initial decrease in the pioglitazone group was slower but was sustained for the duration of the trial. HbA1c levels were significantly better in the pioglitazone group from week 72 onward.

Measurement of HDL-cholesterol levels showed a highly significant (P < .001) 13% increase in the pioglitazone group that was maintained throughout the trial. Glimepiride had little effect on HDL-cholesterol levels. Dr. Mazzone noted that this difference could have played a role in the pioglitazone's favorable effect on CIMT.

There was also a 13.5% decrease in triglyceride levels in the pioglitazone group with a 2.1% increase in the glimepiride group (P < .001). No significant between-group differences were seen in LDL-cholesterol levels or systolic blood pressure.

Ten cardiovascular events (1 nonfatal myocardial infarction, 1 nonfatal stroke, and 8 coronary revascularizations) occurred in the glimepiride group compared with 4 events (1 hospitalization for congestive heart failure and 3 coronary revascularizations) in the pioglitazone group.

"Our results demonstrated the beneficial effect of pioglitazone compared to glimepiride on CIMT," Dr. Mazzone concluded.


[Presentation title: Effects of Pioglitazone Compared to Glimepiride on Carotid Intima-Media Thickness (CIMT) in Type 2 Diabetes - Results of the CHICAGO Study.]

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