The ACCORD-Lipid study: implications for treatment of dyslipidemia in Type 2 diabetes mellitus.

Patients with Type 2 diabetes mellitus (T2DM) are at high risk of developing cardiovascular disease (CVD). Treatment of diabetic dyslipidemia, comprised mainly of hypertriglyceridemia, and low HDL-C, with either statin or fibrate monotherapy, is moderately effective at reversing the abnormal lipid levels, but does not completely reverse the risk of CVD. Combination therapy with a statin and fibrate more effectively treats diabetic dyslipidemia; however, neither the impact on CVD risk nor the safety profile of statin-fibrate combined treatment had been tested in a large randomized trial. The Action to Control Cardiovascular Risk in Diabetes (ACCORD)-Lipid trial tested the hypothesis that combination therapy with a fibrate and statin would more effectively prevent major CVD events in a high-risk population of patients with T2DM compared with statin monotherapy. In ACCORD-Lipid, over 5000 patients were treated with fenofibrate plus simvastatin versus simvastatin alone. Although combination therapy did not significantly reduce CVD event rates in the ACCORD-Lipid cohort as a whole, a predefined subgroup of participants with the combination of significant hypertriglyceridemia and low HDL-C experienced a 31% lower event rate with combination therapy. Post hoc analyses conducted in similar subsets in previous fibrate monotherapy trials were concordant with these findings in ACCORD-Lipid. Combination therapy was well tolerated and safe, with no detectable increase in myopathy. The implications of the ACCORD-Lipid findings for the treatment of dyslipidemia in patients with T2DM are discussed.