Precision medicine in type 2 diabetes: insight and validation of genetic-dependent cardiovascular response to fenofibrate. A genetic-driven randomized clinical trial.

Fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR-a) agonist known to improve diabetic dyslipidemia, has been proposed as a drug to prevent cardiovascular disease (CVD) in type 2 diabetes (T2D). However, results of clinical trials have been mixed. Supporting the hypothesis that these disappointing results hide a genetic heterogeneity in the CVD response to fenofibrate, we have identified a common genetic variant in the gene coding for PPAR-a showing dramatic effects on the ability of this drug to reduce CVD events in the ACCORD Lipid trial. Our aim is now to validate these findings by dissecting the pathways through which this variant exerts such modulatory effect, by means of a randomized clinical trial and in vitro studies. If successful, this project will pave the way to a precision medicine approach to prescribe fenofibrate optimally, offering a cardio-protective drug to those patients that are most likely to experience a robust benefit from this medication.