The Reduction of Inflammatory Biomarkers by Statin, Fibrate, and Combination Therapy Among Diabetic Patients With Mixed Dyslipidemia: The DIACOR (Diabetes and Combined Lipid Therapy Regimen) Study Original Research Article

Objectives The primary objective was to determine the effect of statin-fibrate combination therapy on inflammatory biomarkers in patients with diabetes. Background Atherosclerosis is a long-term, chronic inflammatory disease that is exacerbated in patients with diabetes. Methods Patients (n = 300) with type II diabetes, mixed dyslipidemia (2 or more of low-density lipoprotein ≥100 mg/dl, triglycerides ≥200 mg/dl, or high-density lipoprotein <40 mg/dl), and no history of coronary heart disease were randomly assigned to receive simvastatin 20 mg, fenofibrate 160 mg, or a combination of simvastatin 20 mg and fenofibrate 160 mg daily. At 12 weeks after randomization, we measured levels of high-sensitivity C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2). Results At 12 weeks, median hsCRP was significantly reduced (−14.6%, p = 0.004) from baseline, but the effect did not differ between treatments. The effect was greatest among patients with baseline hsCRP levels >2.0 mg/l (fenofibrate = −18.9%, p = 0.002 vs. baseline; simvastatin = −24.8%, p < 0.0001; combination = −27.3%, p = 0.002). Likewise, median Lp-PLA2 levels in the overall study population were significantly reduced (−16.8%, p < 0.0001), and the effect did not differ among treatments. This effect also was greatest among patients with increased baseline levels of Lp-PLA2 greater than the median of 320.9 ng/ml (fenofibrate = −41.3%, p < 0.0001; simvastatin = −47.5%, p < 0.0001; combination = −46.8%, p < 0.0001). Conclusions Simvastatin, fenofibrate, and combination therapy each lowered hsCRP and Lp-PLA2. These anti-inflammatory effects were most pronounced among patients with increased baseline levels. Combination therapy was no more effective than either form of monotherapy. (The DIACOR Study; http://www.clinicaltrials.gov/ct/show/NCT00309712?order=1)