Liu Mengying, Lim Seok Ting, Song Weihua, Coffman Thomas M, Wang Xiaomeng
Duke-NUS Medical School, Singapore 169857, Singapore.; Singapore Eye Research Institute, Singapore 169856, Singapore.
Duke-NUS Medical School, Singapore 169857, Singapore.; Singapore Eye Research Institute, Singapore 169856, Singapore..
Trends Pharmacol Sci. 2025 Aug 19. doi: 10.1016/j.tips.2025.07.014.
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.
糖尿病视网膜病变（DR）和肾病（DN）是糖尿病主要的微血管并发症，但目前的治疗方法仍然不足。非诺贝特是一种被批准用于治疗血脂异常的过氧化物酶体增殖物激活受体（PPAR）-α激动剂，其对视网膜和肾脏的保护作用超出了脂质调节范畴，因而受到关注。新出现的临床前和临床证据凸显了非诺贝特的多效性作用（抗炎、抗氧化、神经保护和抗纤维化），这些作用通过PPAR-α依赖性和非依赖性途径介导。这些特性支持了其在DR和DN中潜在的益处，即使在血脂正常的个体中也是如此。在本综述中，我们将机制性见解与临床结果相结合，批判性地评估具有里程碑意义的试验，并探索非诺贝特新出现的分子靶点。我们强调非诺贝特的多功能作用，并提出提高其在糖尿病微血管并发症中临床效用的策略。
