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).
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.


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.
Kahn
Steven E
SE
Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle,Washington, USA. skahn@u.washington.edu
Haffner
Steven M
SM
Viberti
Giancarlo
G
Herman
William H
WH
Lachin
John M
JM
Kravitz
Barbara G
BG
Yu
Dahong
D
Paul
Gitanjali
G
Holman
Rury R
RR
Zinman
Bernard
B
D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005905:Glyburide / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*; D013995:Time; D016896:Treatment Outcome; D015430:Weight Gain / Q000187:drug effects
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D002097:C-Reactive Protein; D008687:Metformin; D005905:Glyburide