What is the role of fenofibrate (Fenofibrate) in diabetic retinopathy?

From the Guidelines

Fenofibrate is a recommended adjunctive treatment for diabetic retinopathy, particularly in individuals with dyslipidemia, as it may slow retinopathy progression, especially in those with very mild non-proliferative diabetic retinopathy at baseline. This recommendation is based on the most recent evidence from the 2024 standards of care in diabetes, which suggests that fenofibrate can be beneficial in slowing retinopathy progression 1. The exact mechanism by which fenofibrate exerts its protective effects on the retina is not fully understood, but it is thought to involve the activation of peroxisome proliferator-activated receptor alpha (PPAR-α), which reduces inflammation, oxidative stress, and abnormal blood vessel formation in the retina.

Key points to consider when using fenofibrate for diabetic retinopathy include:

• The typical dosage is 145 mg daily, though some clinicians may use 160 mg daily
• Fenofibrate should be used alongside optimal glycemic control, blood pressure management, and regular ophthalmologic examinations, not as a replacement for these measures
• The medication is generally well-tolerated but requires monitoring of liver function and muscle symptoms
• Patients with severe kidney disease should use reduced doses or avoid it altogether

The benefits of fenofibrate in diabetic retinopathy have been established in major clinical trials, such as the FIELD and ACCORD-Eye studies, which demonstrated significant reductions in retinopathy progression, particularly in patients with pre-existing retinopathy 1. While primarily used to treat dyslipidemia, fenofibrate's protective effects on the retina appear to be independent of its lipid-lowering properties. Overall, fenofibrate is a valuable adjunctive treatment for diabetic retinopathy that can slow disease progression and reduce the need for laser therapy, and its use should be considered in patients with dyslipidemia and diabetic retinopathy.

From the Research

Role of Fenofibrate in Diabetic Retinopathy

The role of fenofibrate in diabetic retinopathy is supported by several studies, which suggest that it can reduce the progression of the disease and the need for laser treatment.

• Fenofibrate has been shown to reduce the progression of diabetic retinopathy by 31% in the FIELD study and by 40% in the ACCORD Eye study 2, 3.
• The putative mechanisms implicated in the mode of action of fenofibrate involve lipid and nonlipid pathways, including beneficial effects on apoptosis, oxidative stress, inflammation, blood-retinal barrier breakdown, and neuroprotection 2.
• Fenofibrate regulates the expression of many different genes, with a range of beneficial effects on lipid control, inflammation, angiogenesis, and cell apoptosis, which are believed to be important in the development of diabetic retinopathy 4.
• Experimental studies have demonstrated improved survival of retinal endothelial and pigment epithelial cells in conjunction with reduced stress signaling under diabetic conditions, and fenofibrate improves retinal outcomes in rodent models of diabetes and retinal neovascularization 4, 5.

Clinical Evidence

Clinical evidence from large, randomized trials such as the FIELD and ACCORD studies suggests that fenofibrate can be used as an adjunctive treatment for early diabetic retinopathy in patients with type 2 diabetes mellitus 2, 3, 6.

• The FIELD study showed that fenofibrate reduced the first laser treatment by 31% and progression of diabetic retinopathy by 5.0% over 5 years 2.
• The ACCORD Eye study showed that fenofibrate with simvastatin resulted in a 40% reduction in the odds of retinopathy progressing over 4 years, compared with simvastatin alone 3.
• The results of these studies suggest that fenofibrate can be a useful adjunctive treatment to modifiable risk factor control and regular ophthalmic review in the management of diabetic retinopathy 4, 5, 6.

Potential Benefits and Limitations

The potential benefits of fenofibrate in diabetic retinopathy include its ability to reduce disease progression and the need for laser treatment, as well as its beneficial effects on lipid control, inflammation, and cell apoptosis.

• However, further clinical trials are needed to establish the benefits of fenofibrate in other forms of diabetes, including type 1 diabetes, and to refine how best to use fenofibrate in the management of diabetic retinopathy 4, 5.
• Additionally, the incorporation of fenofibrate into clinical practice should be continually revised as more information becomes available 4.