Rosiglitazone Decreases C-Reactive Protein to a Greater Extent Relative to Glyburide and Metformin Over 4 Years Despite Greater Weight Gain

doi:10.2337/dc09-1661

Rosiglitazone Decreases C-Reactive Protein to a Greater Extent Relative to Glyburide and Metformin Over 4 Years Despite Greater Weight Gain

Observations from A Diabetes Outcome Progression Trial (ADOPT)

Steven E. Kahn, MB, CHB¹,
Steven M. Haffner, MD²,
Giancarlo Viberti, MD³,
William H. Herman, MD⁴,
John M. Lachin, SCD⁵,
Barbara G. Kravitz, MS⁶,
Dahong Yu, PHD⁶,
Gitanjali Paul, PHD⁶,
Rury R. Holman, MD⁷,
Bernard Zinman, MD⁸ and
for A Diabetes Outcome Progression Trial (ADOPT) Study Group*

¹Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, Washington;
²University of Texas Health Science Center at San Antonio, San Antonio, Texas;
³King's College London School of Medicine, London, U.K.;
⁴Departments of Internal Medicine and Epidemiology, University of Michigan, Ann Arbor, Michigan;
⁵The Biostatistics Center, The George Washington University, Rockville, Maryland;
⁶GlaxoSmithKline, King of Prussia, Pennsylvania;
⁷Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford, U.K.;
⁸Samuel Lunenfeld Research Institute, Mount Sinai Hospital and University of Toronto, Ontario, Canada.

Corresponding author: Steven E. Kahn, skahn{at}u.washington.edu.

Abstract

OBJECTIVE C-reactive protein (CRP) is closely associated with obesity and cardiovascular disease in both diabetic and nondiabetic populations. In the short term, commonly prescribed antidiabetic agents have different effects on CRP; however, the long-term effects of those agents are unknown.

RESEARCH DESIGN AND METHODS In A Diabetes Outcome Progression Trial (ADOPT), we examined the long-term effects of rosiglitazone, glyburide, and metformin on CRP and the relationship among CRP, weight, and glycemic variables in 904 subjects over 4 years.

RESULTS Baseline CRP was significantly correlated with homeostasis model assessment of insulin resistance (HOMA-IR), A1C, BMI, waist circumference, and waist-to-hip ratio. CRP reduction was greater in the rosiglitazone group by −47.6% relative to glyburide and by −30.5% relative to metformin at 48 months. Mean weight gain from baseline (at 48 months) was 5.6 kg with rosiglitazone, 1.8 kg with glyburide, and −2.8 kg with metformin. The change in CRP from baseline to 12 months was correlated positively with change in BMI in glyburide (r = 0.18) and metformin (r = 0.20) groups but not in the rosiglitazone (r = −0.05, NS) group. However, there was no longer a significant correlation between change in CRP and change in HOMA-IR, A1C, or waist-to-hip ratio in any of the three treatment groups.

CONCLUSIONS Rosiglitazone treatment was associated with durable reductions in CRP independent of changes in insulin sensitivity, A1C, and weight gain. CRP in the glyburide and metformin groups was positively associated with changes in weight, but this was not the case with rosiglitazone.

Footnotes

↵*A list of members of A Diabetes Outcome Progression Trial (ADOPT) Study Group can be found in ref. 22.
Clinical trial registry no. NCT00279045, clinicaltrials.gov.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
- Received September 5, 2009.
- Accepted September 28, 2009.