DALLAS — Treatment with rosiglitazone was linked with markedly reduced serum levels of C-reactive protein and regression of carotid atherosclerosis in a study with about 70 patients with type 2 diabetes. In contrast, treatment with metformin was unable to produce either of these effects.
These findings “point to potential superior efficacy of thiazolidinediones over metformin for cardiovascular outcomes, but direct studies are needed,” Dr. Allen J. Taylor said at the annual scientific sessions of the American Heart Association.
“The data are consistent with the biologically plausible hypothesis of a direct antiatherosclerotic effect of rosiglitazone,” said Dr. Taylor, chief of cardiology services and professor of medicine at Walter Reed Army Medical Center in Washington.
The study, done at Walter Reed, had no commercial sponsorship.
The researchers enrolled patients with type 2 diabetes and a hemoglobin A1c level of more than 7% despite treatment with diet or a sulfonylurea drug. Patients were randomized to treatment on an open-label basis to either 4 mg rosiglitazone (Avandia) daily or 850 mg metformin (Glucophage) twice daily. The randomization was stratified to assign patients with similar levels of statin use to both treatment groups.
The primary end point was the change in serum levels of C-reactive protein (CRP) after 24 weeks of treatment. In the rosiglitazone group, serum CRP fell by about half after the first 2 weeks of treatment, from an average of 6 mg/L at baseline to a mean of 3 mg/L. The CRP level continued to gradually drop during subsequent treatment, and after 24 weeks, was at an average of 2 mg/L in 37 evaluable patients.
Every time CRP levels were measured, after 2, 4, 16, and 24 weeks of treatment, the reductions were significantly different, compared with baseline.
In contrast, metformin produced no significant drop in CRP at any of the measured times in 38 evaluable patients. The secondary end point was a change in the ultrasound measurement of carotid intimal medial thickness after 24 weeks of treatment, compared with baseline levels.
In the rosiglitazone group, the mean carotid intimal media thickness regressed by an average of 0.069 mm in 35 evaluable patients, an indicator of reduced atherosclerosis. The average change in 38 patients treated with metformin was atherosclerosis progression of 0.011 mm. The difference between the two groups was statistically significant.
An exploratory analysis indicated a modest statistical link between the change in serum CRP and the change in carotid intimal medial thickness, Dr. Taylor said.
Neither drug had an effect on serum levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, or triglycerides.