A randomized trial of the effects of rosiglitazone and metformin on inflammation and subclinical atherosclerosis in patients with type 2 diabetes.
BACKGROUND
Metformin and rosiglitazone both improve glycemic control in type 2 diabetes mellitus, however may possess different anti-inflammatory and anti-atherosclerotic properties. We investigated the effects of these medications on high-sensitivity C-reactive protein (hsCRP) and carotid artery intima-media thickness (CIMT) to determine their relative potential to reduce cardiovascular risk independent of their antihyperglycemic actions.


METHODS
Ninety-two subjects with suboptimally controlled diabetes mellitus (hemoglobin A1c [HbA1c] >7.0%) were assigned to therapy with either rosiglitazone 4 mg once daily or metformin 850 mg twice daily for 24 weeks. The primary end point was the change in hsCRP after 24 weeks. The change in CIMT was prespecified as a secondary end point.


RESULTS
Metformin and rosiglitazone treatment led to similar significant improvements in glycemic control (HbA1c -1.08% in the rosiglitazone group and -1.18% in the metformin group, P = nonsignificant). High-sensitivity C-reactive protein levels decreased by an average of 68% in the rosiglitazone group (5.99 +/- 0.88 to 1.91 +/- 0.28 mg/L, P < .001), compared with a nonsignificant 4% reduction in hsCRP with metformin (5.69 +/- 0.83 to 5.46 +/- 0.92 mg/L; P = nonsignificant). Maximal CIMT progressed in the metformin group (+0.084 +/- 0.038 mm), whereas regression of maximal CIMT was observed in the rosiglitazone group (-0.037 +/- 0.031 mm; P = .02 for the between group comparison). Similar changes were observed for mean CIMT. The change in hsCRP and maximal CIMT were related in a multivariable model controlling for changes in HbA1c and lipid parameters (r = .31; P = .01).


CONCLUSIONS
Rosiglitazone, compared to metformin, induced a prompt and profound reduction in hsCRP levels independent of its effect on glycemia. This change was associated with regression of CIMT after 24 weeks.
Stocker
Derek J
DJ
Endocrine, Diabetes, and Metabolism Service, Department of Medicine, Walter Reed Army Medical Center, Washington, DC 20307, USA.
Taylor
Allen J
AJ
Langley
Roy W
RW
Jezior
Matthew R
MR
Vigersky
Robert A
RA
D000368:Aged; D050197:Atherosclerosis / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D015999:Multivariate Analysis; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000627:therapeutic use*; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D014665:Vasodilator Agents; D000077154:Rosiglitazone; D002097:C-Reactive Protein; D008687:Metformin