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Impact of Selective Peroxisome Proliferator-Activated Receptor (PPAR)-α Modulators and Fibrates on Microvascular

Lucas Lage Marinho1,2, Matheus Laterza Ribeiro3, Patrick R Lawler4,5

  • 1McGill University Health Centre, McGill University, 1001 boulevard Décarie, Montreal, H4A3J1, Canada. lucas.marinho@mail.mcgill.ca.

Current Atherosclerosis Reports
|March 20, 2025
PubMed
Abstract

Insights

Fibrates and selective PPAR-alpha modulators (SPPARM-α) show promise in preventing diabetic microvascular complications like retinopathy and nephropathy. Further trials are needed to confirm their role in modern diabetes care.

Area of Science:

  • Endocrinology
  • Pharmacology
  • Diabetology

Background:

  • Diabetic microvascular complications remain a leading cause of morbidity.
  • Residual risk persists despite current diabetes management strategies.
  • Fibrates and SPPARM-α offer potential therapeutic avenues beyond lipid modification.

Purpose of the Study:

  • To review the role of fibrates and pemafibrate (a SPPARM-α) in diabetic microvascular disease.
  • To assess their potential in mitigating residual risk in retinopathy, nephropathy, neuropathy, and peripheral vascular disease.

Main Methods:

  • Review of existing literature and secondary analyses of large clinical trials.
  • Examination of pharmacotherapies beyond lipid-lowering effects.
  • Evaluation of anti-inflammatory, antioxidant, and endothelial-protective actions.

Main Results:

  • Fibrates and SPPARM-α demonstrate efficacy in slowing retinopathy progression and reducing albuminuria.
  • These agents may prevent minor amputations and reduce incidence of diabetic foot ulcers and gangrene.
  • Pemafibrate shows potential for enhanced efficacy and safety compared to conventional fibrates.

Conclusions:

  • Fibrates and SPPARM-α agonists are promising for preventing diabetic microvascular complications.
  • Their benefits in reducing microvascular damage support broader clinical adoption.
  • Further randomized trials are essential to validate efficacy in contemporary diabetes care.
Keywords:
Diabetes mellitusFibratesNephropathyNeuropathyRetinopathySPPARM alpha agonists

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