Impact of Selective Peroxisome Proliferator-Activated Receptor (PPAR)-α Modulators and Fibrates on Microvascular Disease: Is There Still Room?

Objective: This review examines the role of fibrates and the selective PPAR-alpha modulators (SPPARM-α), pemafibrate, in diabetic microvascular disease. It reviews their potential to mitigate residual risk in retinopathy, nephropathy, neuropathy and peripheral vascular disease.

Results: These pharmacotherapies, beyond their lipid-lowering effects, may exert anti-inflammatory, antioxidant, and endothelial-protective actions. Secondary analyses of large clinical trials supports their efficacy in slowing retinopathy progression, reducing albuminuria, and preventing minor amputations. Recent analyses suggest that pemafibrate offers an enhanced efficacy and safety profile compared to conventional fibrate and may lower the incidence of diabetic foot ulcers and gangrene. Fibrates and SPPARM-α agonists represent promising therapies to prevent diabetic microvascular complications. Their benefits in reducing microvascular damage support their broader adoption in clinical practice. However, additional dedicated randomized trials are essential to validate the efficacy of those agents in contemporary diabetes care era and to address the growing burden of diabetes-related microvascular complications.