Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial.
BACKGROUND
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.


METHODS
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.


METHODS
Pioglitazone hydrochloride (15-45 mg/d) or glimepiride (1-4 mg/d) as an active comparator.


METHODS
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, HbA(1c) value, and statin use.


CONCLUSIONS
Over an 18-month treatment period in patients with type 2 DM, pioglitazone slowed progression of CIMT compared with glimepiride.


BACKGROUND
clinicaltrials.gov Identifier: NCT00225264
Mazzone
Theodore
T
Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Illinois College of Medicine, Chicago 60612, USA. tmazzone@uic.edu
Meyer
Peter M
PM
Feinstein
Steven B
SB
Davidson
Michael H
MH
Kondos
George T
GT
D'Agostino
Ralph B
RB
Perez
Alfonso
A
Provost
Jean-Claude
JC
Haffner
Steven M
SM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control; D002339:Carotid Arteries / Q000033:anatomy & histology / Q000000981:diagnostic imaging*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000627:therapeutic use*; D017539:Tunica Intima / Q000033:anatomy & histology / Q000000981:diagnostic imaging*; D014463:Ultrasonography
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C057619:glimepiride; D000077205:Pioglitazone