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Diabetes and Combined Lipid Therapy Regimen - DIACOR
Description:
The goal of the trial was to evaluate treatment with simvastatin, fenofibrate, or a combination of simvastatin and fenofibrate among patients with type II diabetes and mixed dyslipidemia.
Study Design
Study Design:
Patients Enrolled: 300
Mean Follow Up: 12 weeks
Mean Patient Age: Mean age 61 years
Female: 45
Patient Populations:
Controlled type II diabetes mellitus (hemoglobin A1C ≥9%); stable dosing of hypoglycemic therapy regimen for the previous 3 months; dyslipidemia, defined as having at least two of the following: LDL ≥100 mg/dl, triglycerides ≥200 mg/dl, high-density lipoprotein <40 mg/dl
Exclusions:
Plasma creatine kinase >50% above the upper limit of normal (ULN); known history of coronary heart disease, myopathy, or rhabdomyolysis; active liver disease or serum alanine aminotransferase or aspartate aminotransferase levels >30% above the ULN; history of alcohol consumption ≥2 drinks/day or ≥10 drinks/week; use of lipid-lowering agents taken within 6-8 weeks prior to study, depending on agent; serum creatinine >1.5 mg/dl; uncontrolled hypertension; proteinuria; hypothyroidism; known hypersensitivity to statins or fibrates
Primary Endpoints:
Rate of triglyceride <200 mg/dl at 12 weeks
Drug/Procedures Used:
Patients were randomized to simvastatin (20 mg; n = 100), fenofibrate (160 mg; n = 100), or a combination of simvastatin 20 mg and fenofibrate 160 mg (n = 100) for 12 weeks. Fasting lipids were measured at baseline, 6 weeks, and 12 weeks.
Principal Findings:
Baseline characteristics were well balanced between groups, with diabetes controlled by oral antidiabetic agents in 87% of patients, insulin in 10.7%, and diet in 15.7%.
At 12 weeks, low-density lipoprotein (LDL) cholesterol was significantly reduced from baseline in all three treatment groups (-5.6% with fenofibrate, -34.1% with simvastatin, -29.1% with combined; p < 0.001 vs. baseline for each group), with greater decreases in the simvastatin and combined group compared with the fenofibrate alone group (p < 0.0001). Triglycerides were also reduced compared to baseline in all groups (-38.2% with fenofibrate, -24.8% with simvastatin, -49.4% with combined; p < 0.001 vs. baseline for each), with the largest reductions seen with the combination group (p < 0.0001 vs. simvastatin alone; p = 0.07 vs. fenofibrate).
High-sensitivity C-reactive protein (hs-CRP) was significantly reduced from baseline in the simvastatin groups (-16.0%, p = 0.04), with nonsignificant reductions in the fenofibrate group (-14.7%, p = 0.17) and the combination group (-16.0%, p = 0.10), with no difference between groups. LpPLA2 was significantly reduced from baseline in all three treatment groups (-26.9% with fenofibrate, -34.5% with simvastatin, -36.2% with combined; p < 0.001 vs. baseline for each group), with no difference between groups. The frequency of adverse events was similar between groups.
Interpretation:
Among patients with type II diabetes and mixed dyslipidemia, treatment with fenofibrate, simvastatin, or the combination was associated with reductions in LDL, triglycerides, and LpPLA2 at 12 weeks compared with baseline, with larger reductions in triglycerides seen with combination therapy than the other groups.
While there was no additional benefit on hs-CRP, the present trial demonstrated the additional triglyceride-lowering benefits of fenofibrate when combined with simvastatin on top of either therapy alone. However, the trial was not powered to evaluate clinical events. The upcoming ACCORD trial will evaluate treatment with fenofibrate compared with placebo in diabetic patients who are also treated with simvastatin, which will provide a more definitive answer of the clinical benefit of fenofibrate in the setting of statin therapy.
References:
Muhlestein JB, May HT, Jensen JR, et al. 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. J Am Coll Cardiol 2006;48:396–401.
Keywords: Fenofibrate, Insulin, C-Reactive Protein, Hemoglobins, Hyperlipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Diabetes Mellitus, Type 2, Hypolipidemic Agents, Hypoglycemic Agents, Hypercholesterolemia, Simvastatin, Fasting
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