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C-reactive protein further reduced with TZDs
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Patients with type 2 diabetes who were treated with rosiglitazone experienced more rapid and durable reductions in C-reactive protein despite greater weight gain after four years compared with patients treated with glyburide and metformin, according to results of a subgroup analysis of the ADOPT trial.
Further, the effect was independent of changes in insulin sensitivity, HbA1c and weight gain.
For the subgroup analysis of ADOPT, researchers randomly assigned patients to one of three treatment arms: rosiglitazone 4 mg daily (n=304); glyburide 2.5 mg daily (n=302); or metformin 500 mg daily (n=298). The researchers assessed the long-term effects of each treatment on the reduction of C-reactive protein and the relationship between C-reactive protein, weight and glycemic levels after four years.
Of the 904 patients, 706 remained at one year (rosiglitazone, n=239; glyburide, n=220; metformin, n=247) and 413 at four years (rosiglitazone, n=153; glyburide, n=112; metformin, n=148).
At baseline, C-reactive protein levels were significantly associated with insulin resistance, HbA1c, BMI, waist circumference and waist-to-hip ratio.
At four years, C-reactive protein reduction was greater in the rosiglitazone group by –47.6% (P<.001) compared with glyburide, and by –30.5% (P=.004) compared with metformin.
Treatment with glyburide and metformin was associated with moderate, gradual reductions in C-reactive protein. However, unlike with rosiglitazone, the researchers reported a positive association between the reduction and changes in weight; the reduction was independent of glycemic control and insulin sensitivity.
Weight increased by 5.6 kg in the rosiglitazone group, 1.8 kg in the glyburide group and decreased by 2.8 kg in the metformin group at year four.
Changes in C-reactive protein levels from baseline to one year were positively associated with changes in BMI for the glyburide (R=0.18) and metformin (R=0.20) groups only. There was no longer a significant association between changes in C-reactive protein levels and changes in insulin resistance, HbA1c or waist-to-hip ratio for any of the treatment groups.
“The possible value of C-reactive protein reduction by glucose-lowering therapy for future cardiovascular disease events needs to be considered with other CVD risk factors in patients with type 2 diabetes,” the researchers concluded.
Kahn SE. Diabetes Care. 2010;33:177-183.