Effect of Pioglitazone Compared with Glimepiride on Carotid Intima-media Thickness in Type 2 Diabetes

Effect of Pioglitazone Compared with Glimepiride on Carotid Intima-media Thickness in Type 2 Diabetes

Mazzone Theodore
US Cardiovascular Disease 2007
Published: July 2007
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Objective
To evaluate the effect of pioglitazone versus glimepiride on changes in CIMT of the common carotid artery in patients with type 2 DM. Design, Setting, and Participants Randomized, double-blind, comparator-controlled, multicenter trial in patients with type 2 DM conducted at 28 clinical sites in the multiracial/ethnic Chicago metropolitan area between October 2003 and May 2006. The treatment period was 72 weeks (one-week followup). CIMT images were captured by a single ultrasonographer at one center and read by a single treatment-blinded reader using automated edge-detection technology. Participants were 462 adults (mean age, 60 [standard deviation, SD, 8.1] years; mean body mass index, 32 [SD, 5.1]) with type 2 DM (mean duration, 7.7 [SD, 7.2] years; mean HbA1c value, 7.4% [SD, 1.0%]), either newly diagnosed or currently treated with diet and exercise, sulfonylurea, metformin, insulin, or a combination thereof. Interventions Pioglitazone hydrochloride (15–45mg/d) or glimepiride (1–4mg/d) as an active comparator. Main Outcome Measure Absolute change from baseline to final visit in mean posterior-wall CIMT of the left and right common carotid arteries.

Results
Mean change in CIMT was lower with pioglitazone versus glimepiride at all time-points (weeks 24, 48, 72). At week 72, the primary endpoint of progression of mean CIMT was less with pioglitazone versus glimepiride (-0.001mm versus +0.012mm, respectively; difference, -0.013mm; 95% confidence interval, -0.024 to -0.002; p=0.02). Pioglitazone also slowed progression of maximum CIMT compared with glimepiride (0.002mm versus 0.026mm, respectively, at 72 weeks; difference, -0.024mm; 95% confidence interval, -0.042 to -0.006; p=0.008). The beneficial effect of pioglitazone on mean CIMT was similar across pre-specified subgroups based on age, sex, systolic blood pressure, duration of DM, body mass index, HbA1c value, and statin use.

Conclusion
Over an 18-month treatment period in patients with type 2 DM, pioglitazone slowed progression of CIMT compared with glimepiride. For full results and statistical analysis, please view original paper (JAMA, 2006;296) available at: doi:10.1001/jama.296.21.joc60158

Patients with type 2 diabetes mellitus (DM) have a marked increase in the risk of myocardial infarction (MI), and a substantially worse prognosis after MI compared with patients without diabetes.1;3 In recent years, it has become apparent that optimal control of blood pressure and low-density lipoprotein cholesterol (LDL-C) level can substantially reduce excess cardiovascular risk in patients with diabetes.4;6 However, even with optimal control of these potent cardiovascular risk factors, incremental risk for cardiovascular events remains high compared with individuals without diabetes.2;3,6 New approaches are, therefore, needed to further reduce cardiovascular risk in patients with diabetes.

Emerging evidence suggests that thiazolidinediones could be useful for reducing cardiovascular risk. In isolated vessel-wall cells, troglitazone, pioglitazone, and rosiglitazone have been shown to modulate gene expression in a manner that would be predicted to be atheroprotective in vivo.7;8 In humans, these agents have been shown to have beneficial effects on systemic inflammatory and coagulation markers, lipoprotein profile, and endothelial cell function.9;12 Some of these beneficial effects may be independent of effects on glycemia.13;15 In animal models of atherosclerosis, thiazolidinediones have been shown to reduce atherosclerotic plaque area independent of changes in glycemia or lipid profile.16;17

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