Adding a Fibrate to Statin Therapy in Type 2 Diabetes

Dyslipidemia is a common comorbidity in patients with type 2 diabetes. Elevated lipids are thought to contribute to the development of cardiovascular disease. Specifically, elevated LDL promotes atherosclerotic placque production that can eventually lead to a heart attack or stroke. Patients with increased LDL levels are often placed on a drug known as a statin, which inhibits endogenous synthesis of cholesterol and lowers LDL.

Several clinical trials have demonstrated that statin use in type 2 diabetics can reduce the rate of cardiovascular events, however there is room for improvement. Fenofibrate, another drug indicated for dyslipidemia, has had mixed success in the literature in reducing adverse events from cardiovascular disease in type 2 diabetics. A clinical trial, recently published in The New England Journal of Medicine, assessed the use of Fenofibrate as an adjunct to improve simvastatin (a statin) therapy.

Eligible participants for the trial were type 2 diabetics between the ages of 55 and 79 with subclinical cardiovascular disease, or between 40 and 79 with established cardiovascular disease. Required lab values included an LDL of 60-180 mg/dL, HDL below 55 mg/dL, triglycerides below 750 mg/dL if not not on a lipid lowering therapy and below 400 mg/dL if on a lipid controlling drug. 5,518 patients received open label simvastatin and were blinded to receive either fenofibrate or placebo.

The primary outcome of the trial was the first "major cardiovascular event", or death. The investigators found that the rate of the primary outcome was 2.2% in the fenofibrate group and 2.4% in the placebo group. Fenofibrate in addition to simvastatin did not provide any additional benefit in preventing death. A subgroup analyisis suggested that sex could be a contributing factor in attaining any benefit from the addition of fenofibrate to a statin.

Men demonstrated a benefit from the addition of fenofibrate in regards to the rate of cardiovascular events, while women conversely demonstrated an increased risk. The authors pointed out this was in contrast to previously published work that demonstrated sex is not a determinant factor in fenofibrate efficacy. The subgroup analysis also suggested that type 2 diabetics with high triglycerides and low HDL may benefit from fenofibrate in addition to a statin.

This clinical trial suggests that fenofibrate in addition to simvastain in type 2 diabetics does not offer any benefit in preventing cardiovascular events or death. The authors caution against routine fenofibrate use in type 2 diabetics in addition to statin therapy. However, the subgroup analysis suggests that the drug may have a potential use for type 2 diabetics with high triglyceride levels and low HDL. An additional clinical trial focusing on these subgroups is needed to confirm this result.

References:

ACCORD Study Group, et, al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1563-74.