Effect of Pioglitazone Compared With Glimepiride on Carotid Intima-Media Thickness in Type 2 Diabetes
A Randomized Trial
- Theodore Mazzone, MD;
- Peter M. Meyer, PhD;
- Steven B. Feinstein, MD;
- Michael H. Davidson, MD;
- George T. Kondos, MD;
- Ralph B. D’Agostino, Sr, PhD;
- Alfonso Perez, MD;
- Jean-Claude Provost, MD;
- Steven M. Haffner, MD
- Author Affiliations: Department of Medicine, Section of Endocrinology, Diabetes and Metabolism (Dr Mazzone) and Section of Cardiology (Dr Kondos), University of Illinois College of Medicine, Chicago; Departments of Preventive Medicine (Dr Meyer) and Medicine, Section of Cardiology (Drs Feinstein and Davidson), Rush University Medical Center, Chicago; Department of Mathematics, Statistics and Consulting Unit, Boston University, Boston, Mass (Dr D’Agostino); Takeda Global Research and Development Inc, Lincolnshire, Ill (Dr Perez); Synarc, Paris, France (Dr Provost); and Department of Medicine, University of Texas Health Science Center at San Antonio (Dr Haffner).
- Corresponding Author: Theodore Mazzone, MD, University of Illinois College of Medicine, Section of Endocrinology, Diabetes and Metabolism, 1819 W Polk St, 612 CMW MC 797, Chicago, IL 60612 (tmazzone{at}uic.edu).
Abstract
Context Carotid artery intima-media thickness (CIMT) is a marker of coronary atherosclerosis and independently predicts cardiovascular events, which are increased in type 2 diabetes mellitus (DM). While studies of relatively short duration have suggested that thiazolidinediones such as pioglitazone might reduce progression of CIMT in persons with diabetes, the results of longer studies have been less clear.
Objective To evaluate the effect of pioglitazone vs 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 (1-week follow-up). CIMT images were captured by a single ultrasonographer at 1 center and read by a single treatment-blinded reader using automated edge-detection technology. Participants were 462 adults (mean age, 60 [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 glycosylated hemoglobin [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 (15-45 mg/d) or glimepiride (1-4 mg/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 less with pioglitazone vs glimepiride at all time points (weeks 24, 48, 72). At week 72, the primary end point of progression of mean CIMT was less with pioglitazone vs glimepiride (−0.001 mm vs +0.012 mm, respectively; difference, −0.013 mm; 95% confidence interval, −0.024 to −0.002; P = .02). Pioglitazone also slowed progression of maximum CIMT compared with glimepiride (0.002 mm vs 0.026 mm, respectively, at 72 weeks; difference, −0.024 mm; 95% confidence interval, −0.042 to −0.006; P = .008). The beneficial effect of pioglitazone on mean CIMT was similar across prespecified 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.
Trial Registration clinicaltrials.gov Identifier: NCT00225264
Published online November 13, 2006 (doi:10.1001/jama.296.21.joc60158).
