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.