Fenofibrate and Carotid Intima-Media Thickness in Adults with Type 2 Diabetes Mellitus: A FIELD Sub-Study

Background: Type 2 Diabetes Mellitus (T2DM) is associated with increased carotid intima-media thickness (CIMT; a validated measure of subclinical atherosclerosis) and an increased incidence of cardiovascular disease. Fenofibrate, a lipid-lowering PPARα agonist, reduces a number of microvascular and macrovascular complications in diabetic adults. We explored the effects of fenofibrate intervention on CIMT in adults with T2DM at high-risk of cardiovascular disease. Methods: In a prospectively designed sub-study of the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study of patients with T2DM, we assessed CIMT in a subset of 422 representative adults, randomised to fenofibrate 200 mg/daily (n = 197) or placebo (n = 225). CIMT was assessed at baseline, two and four years after commencement of the study. Sub-group analyses included examining the effect of fenofibrate on CIMT in those with and without dyslipidaemia (low HDL and high TG) compared with placebo. Results: Fenofibrate and placebo treated subjects were well matched at baseline, with similar CIMT (0.90 ± 0.19 mm). Over four years, CIMT increased similarly in both groups, by 3–4% (p = 0.35 between groups). These results were similar in those with or without dyslipidaemia (p = 0.30). Conclusions: CIMT progressed over four years, with or without fenofibrate treatment in T2DM adults, despite significant improvements in lipoprotein levels. Thus, mechanisms for the reduction of microvascular and macrovascular complications attributed to fenofibrate in the FIELD study appear to be independent of changes in subclinical atherosclerosis.