The
Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study provides an extensive evidence base for the efficacy and tolerability of
fenofibrate treatment in patients with
type 2 diabetes mellitus, predominantly in a primary prevention setting. The FIELD study did not show a significant effect with
fenofibrate on the primary end point,
coronary artery disease death or nonfatal
myocardial infarction (p = 0.16). Treatment with
fenofibrate did reduce all
cardiovascular disease (CVD) events, the secondary end point (by 11%, p = 0.035). The primary end point was reduced by the same percentage. The modest percent reduction in the primary and secondary end points is probably a result of a number of study confounders, notably an excess of
statin drop-in
therapy and disproportionate treatment with other drugs for CVD prevention in the placebo arm. Estimates of relative risk reduction used by the FIELD investigators to equalize the use of
statins in the
fenofibrate and placebo groups suggest a true benefit of treatment on reduction of CVD events of 17%-21%. There was no excess of elevated serum liver
enzymes and no cases of
rhabdomyolysis in patients receiving both
fenofibrate and a
statin. Prevention of microvascular disease, specifically, reduction in the rate of
laser treatment for retinopathy (by 30%, p = 0.0003), progression of
albuminuria (p = 0.002), and nontraumatic
amputations (by 38%, p = 0.011), may well be the most innovative finding of the FIELD study, especially in view of the current lack of effective preventative treatments for
diabetic retinopathy and the need for additional treatments that slow the progression of
diabetic nephropathy. These findings also give impetus to investigate mechanisms by which
fenofibrate and
peroxisome proliferator-activated receptor-alpha activation may protect the endothelium of small blood vessels in patients with
type 2 diabetes.