This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Contact me when this article is cited  Related Content  • Related letters  • Similar articles in JAMA  Social Bookmarking   What's this?

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

JAMA. 2006;296:(doi:10.1001/jama.296.21.joc60158).

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 [HbA_1c] 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, HbA_1c 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).

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).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

RELATED LETTERS

Pioglitazone vs Glimepiride and Carotid Intima-Media Thickness
Dario Giugliano and Katherine Esposito
JAMA. 2007;297(12):1315-1316.
EXTRACT | FULL TEXT  

Pioglitazone vs Glimepiride and Carotid Intima-Media Thickness
Yujiro Kida and Tetsuji Sato
JAMA. 2007;297(12):1316.
EXTRACT | FULL TEXT  

Pioglitazone vs Glimepiride and Carotid Intima-Media Thickness—Reply
Theodore Mazzone
JAMA. 2007;297(12):1316-1317.
EXTRACT | FULL TEXT  

Oral Hypoglycemic Use and the SANDS Trial
Eva L. Evans, Rohit P. Ojha, and Lori A. Fischbach
JAMA. 2008;300(4):389.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

The 6th Annual World Congress on the Insulin Resistance Syndrome
Bloomgarden
Diabetes Care 2009;32:e114-e121.
FULL TEXT  

Hypertriglyceridemic Waist Phenotype Predicts Increased Visceral Fat in Subjects With Type 2 Diabetes
Sam et al.
Diabetes Care 2009;32:1916-1920.
ABSTRACT | FULL TEXT  

Treatment of spontaneously hypertensive rats with rosiglitazone ameliorates cardiovascular pathophysiology via antioxidant mechanisms in the vasculature
Potenza et al.
Am. J. Physiol. Endocrinol. Metab. 2009;297:E685-E694.
ABSTRACT | FULL TEXT  

Review article: Thiazolidinediones and heart failure
Chaggar et al.
Diabetes and Vascular Disease Research 2009;6:146-152.
ABSTRACT  

Oral hypoglycaemic agents, insulin resistance and cardiovascular disease in patients with type 2 diabetes
Hemmingsen et al.
Eur J Endocrinol 2009;161:1-9.
ABSTRACT | FULL TEXT  

A Randomized Trial of Therapies for Type 2 Diabetes and Coronary Artery Disease
The BARI 2D Study Group
NEJM 2009;360:2503-2515.
ABSTRACT | FULL TEXT  

Effect of Ramipril and of Rosiglitazone on Carotid Intima-Media Thickness in People With Impaired Glucose Tolerance or Impaired Fasting Glucose STARR (STudy of Atherosclerosis with Ramipril and Rosiglitazone).
Lonn et al.
J Am Coll Cardiol 2009;53:2028-2035.
ABSTRACT | FULL TEXT  

STARR (STudy of Atherosclerosis with Ramipril and Rosiglitazone) Is the Biggest Big Enough?
Kaski and Cockerill
J Am Coll Cardiol 2009;53:2036-2038.
FULL TEXT  

A Prospective, Multicenter, Randomized Trial to Assess Efficacy of Pioglitazone on In-Stent Neointimal Suppression in Type 2 Diabetes: POPPS (Prevention of In-Stent Neointimal Proliferation by Pioglitazone Study)
Takagi et al.
J Am Coll Cardiol Intv 2009;2:524-531.
ABSTRACT | FULL TEXT  

Relation of Abdominal Fat Depots to Systemic Markers of Inflammation in Type 2 Diabetes
Sam et al.
Diabetes Care 2009;32:932-937.
ABSTRACT | FULL TEXT  

From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus
DeFronzo
Diabetes 2009;58:773-795.
FULL TEXT  

Dominant-Negative Loss of PPAR{gamma} Function Enhances Smooth Muscle Cell Proliferation, Migration, and Vascular Remodeling
Meredith et al.
Arterioscler. Thromb. Vasc. Bio. 2009;29:465-471.
ABSTRACT | FULL TEXT  

Review: Durable glycaemia -- the promised land
Campbell
British Journal of Diabetes & Vascular Disease 2009;9:53-63.
ABSTRACT  

Pioglitazone Inhibits the Expression of Inflammatory Cytokines From Both Monocytes and Lymphocytes in Patients With Impaired Glucose Tolerance
Zhang et al.
Arterioscler. Thromb. Vasc. Bio. 2008;28:2312-2318.
ABSTRACT | FULL TEXT  

Investigation of the vascular and pleiotropic effects of atorvastatin and pioglitazone in a population at high cardiovascular risk
Forst et al.
Diabetes and Vascular Disease Research 2008;5:298-303.
ABSTRACT  

PERISCOPE and the effect of pioglitazone on the progression of coronary artery disease in patients with diabetes
Marx
Diabetes and Vascular Disease Research 2008;5:345-346.
 

Oxidative Stress Regulates Adipocyte Apolipoprotein E and Suppresses Its Expression in Obesity
Espiritu and Mazzone
Diabetes 2008;57:2992-2998.
ABSTRACT | FULL TEXT  

Thiazolidinediones in Type 2 Diabetes: A Cardiology Perspective
Khanderia et al.
The Annals of Pharmacotherapy 2008;42:1466-1474.
ABSTRACT | FULL TEXT  

The Peroxisome Proliferator-Activated Receptor-{gamma} Agonist Pioglitazone Represses Inflammation in a Peroxisome Proliferator-Activated Receptor-{alpha}-Dependent Manner In Vitro and In Vivo in Mice
Orasanu et al.
J Am Coll Cardiol 2008;52:869-881.
ABSTRACT | FULL TEXT  

Approaches to Treatment of Type 2 Diabetes
Bloomgarden
Diabetes Care 2008;31:1697-1703.
FULL TEXT  

Relationship of Abdominal Visceral and Subcutaneous Adipose Tissue With Lipoprotein Particle Number and Size in Type 2 Diabetes
Sam et al.
Diabetes 2008;57:2022-2027.
ABSTRACT | FULL TEXT  

Oral Hypoglycemic Use and the SANDS Trial
Evans et al.
JAMA 2008;300:389-389.
FULL TEXT  

Effect of Diabetes on Progression of Coronary Atherosclerosis and Arterial Remodeling: A Pooled Analysis of 5 Intravascular Ultrasound Trials
Nicholls et al.
J Am Coll Cardiol 2008;52:255-262.
ABSTRACT | FULL TEXT  

Best Practices for Lowering the Risk of Cardiovascular Disease in Diabetes
Triplitt and Alvarez
Diabetes Spectr. 2008;21:177-189.
ABSTRACT | FULL TEXT  

How to interpret figures in reports of clinical trials
Pocock et al.
BMJ 2008;336:1166-1169.
FULL TEXT  

Think Beyond the Numbers, Don't Forget the Patient
Repas
JAOA: Journal of the American Osteopathic Association 2008;108:ii-S4.
FULL TEXT  

Increased High-Density Lipoprotein Cholesterol Predicts the Pioglitazone-Mediated Reduction of Carotid Intima-Media Thickness Progression in Patients With Type 2 Diabetes Mellitus
Davidson et al.
Circulation 2008;117:2123-2130.
ABSTRACT | FULL TEXT  

Comparison of Pioglitazone vs Glimepiride on Progression of Coronary Atherosclerosis in Patients With Type 2 Diabetes: The PERISCOPE Randomized Controlled Trial
Nissen et al.
JAMA 2008;299:1561-1573.
ABSTRACT | FULL TEXT  

Does PERISCOPE Provide a New Perspective on Diabetic Treatment?
Steg and Marre
JAMA 2008;299:1603-1604.
FULL TEXT  

Osteoprotegerin, Thiazolidinediones Treatment, and Silent Myocardial Ischemia in Type 2 Diabetic Patients
Sultan et al.
Diabetes Care 2008;31:593-595.
FULL TEXT  

Beneficial Effects of Pioglitazone on Hypertensive Cardiovascular Injury Are Enhanced by Combination With Candesartan
Nakamura et al.
Hypertension 2008;51:296-301.
ABSTRACT | FULL TEXT  

New Drugs for the Treatment of Diabetes Mellitus: Part I: Thiazolidinediones and Their Evolving Cardiovascular Implications
McGuire and Inzucchi
Circulation 2008;117:440-449.
FULL TEXT  

Thiazolidinediones and Cardiovascular Outcomes in Older Patients With Diabetes
Lipscombe et al.
JAMA 2007;298:2634-2643.
ABSTRACT | FULL TEXT  

Vascular disease in paediatric type 2 diabetes: the state of the art
Vaughan et al.
Diabetes and Vascular Disease Research 2007;4:297-304.
ABSTRACT  

Links Between Adipose Tissue and Thrombosis in the Mouse
Bodary
Arterioscler. Thromb. Vasc. Bio. 2007;27:2284-2291.
ABSTRACT | FULL TEXT  

Nateglinide Reduces Carotid Intima-Media Thickening in Type 2 Diabetic Patients Under Good Glycemic Control
Mita et al.
Arterioscler. Thromb. Vasc. Bio. 2007;27:2456-2462.
ABSTRACT | FULL TEXT  

Carotid Intima-Media Thickness in Confirmed Prehypertensive Subjects: Predictors and Progression
Femia et al.
Arterioscler. Thromb. Vasc. Bio. 2007;27:2244-2249.
ABSTRACT | FULL TEXT  

The Peroxisome Proliferator Activated Receptor-{gamma} Agonist Pioglitazone Increases Number and Function of Endothelial Progenitor Cells in Patients With Coronary Artery Disease and Normal Glucose Tolerance
Werner et al.
Diabetes 2007;56:2609-2615.
ABSTRACT | FULL TEXT  

Artery-Related Differences in Atherosclerosis Expression: Implications for Atherogenesis and Dynamics in Intima-Media Thickness
Dalager et al.
Stroke 2007;38:2698-2705.
ABSTRACT | FULL TEXT  

Pioglitazone and Risk of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: A Meta-analysis of Randomized Trials
Lincoff et al.
JAMA 2007;298:1180-1188.
ABSTRACT | FULL TEXT  

Long-term Risk of Cardiovascular Events With Rosiglitazone: A Meta-analysis
Singh et al.
JAMA 2007;298:1189-1195.
ABSTRACT | FULL TEXT  

Review: Statin plus thiazolidinedione use in patients with diabetes at high cardiovascular risk
Erdmann
British Journal of Diabetes & Vascular Disease 2007;7:211-216.
ABSTRACT  

The Avandia Debate
Bloomgarden
Diabetes Care 2007;30:2401-2408.
FULL TEXT  

Review: Imaging to assess effect of medical therapy in patients with diabetes mellitus
Raggi and Bellasi
British Journal of Diabetes & Vascular Disease 2007;7:157-164.
ABSTRACT  

Avandia Study Gets Mixed Reviews
Law
DOC News 2007;4:20-24.
FULL TEXT  

Point: Recent Long-Term Clinical Studies Support an Enhanced Role for Thiazolidinediones in the Management of Type 2 Diabetes
Kahn and Zinman
Diabetes Care 2007;30:1672-1676.
FULL TEXT  

Combined Low-Dose Pioglitazone, Flutamide, and Metformin for Women with Androgen Excess
Ibanez et al.
J. Clin. Endocrinol. Metab. 2007;92:1710-1714.
ABSTRACT | FULL TEXT  

Fluid Retention With Thiazolidinediones: Does the Mechanism Influence the Outcome?
Lindenfeld and Masoudi
J Am Coll Cardiol 2007;49:1705-1707.
FULL TEXT  

Pioglitazone vs Glimepiride and Carotid Intima-Media Thickness
Giugliano and Esposito
JAMA 2007;297:1315-1316.
FULL TEXT  

Pioglitazone vs Glimepiride and Carotid Intima-Media Thickness
Kida and Sato
JAMA 2007;297:1316-1316.
FULL TEXT  

Kidney disease in diabetology
Schernthaner
Nephrol Dial Transplant 2007;22:703-707.
FULL TEXT  

Relationship of Traditional and Nontraditional Cardiovascular Risk Factors to Coronary Artery Calcium in Type 2 Diabetes
Mazzone et al.
Diabetes 2007;56:849-855.
ABSTRACT | FULL TEXT  

Peroxisome Proliferator Activated Receptors as Transcriptional Nodal Points and Therapeutic Targets
Brown and Plutzky
Circulation 2007;115:518-533.
ABSTRACT | FULL TEXT  

TZD Therapy Thought to Slow Atherosclerosis in People With Diabetes
Goldfarb
DOC News 2007;4:1-12.
FULL TEXT  

Pioglitazone vs. Glimepiride in Type 2 Diabetes
Journal Watch Cardiology 2006;2006:2-2.
FULL TEXT