Beyond lipids: fenofibrate in diabetic retinopathy and nephropathy

Diabetic retinopathy (DR) and nephropathy (DN) are leading microvascular complications of diabetes, yet current therapies remain inadequate. Fenofibrate, a peroxisome proliferator-activated receptor (PPAR)-α agonist approved for dyslipidemia, has gained attention for its protective effects on the retina and kidney that extend beyond lipid modulation. Emerging preclinical and clinical evidence highlights the pleiotropic actions of fenofibrate (anti-inflammatory, antioxidative, neuroprotective, and antifibrotic), mediated through both PPAR-α-dependent and -independent pathways. These properties support its potential benefits in DR and DN, even in normolipidemic individuals. In this review, we integrate mechanistic insights with clinical outcomes, critically evaluate landmark trials, and explore emerging molecular targets of fenofibrate. We highlight the multifunctional actions of fenofibrate and propose strategies to advance its clinical utility in diabetic microvascular complications.