Fenofibrate shown to reduce progression of diabetic retinopathy

Fenofibrate is a PPAR α agonist which is widely used to treat hyperlipidaemia, specifically raised triglyceride. Previous sub-analysis of two large cardiovascular outcomes studies; The FIELD study¹ and the ACCORD study² have indicated potential benefits of Fenofibrate in retinopathy progression. The multicentre LENS trial is the first dedicated study investigating fenofibrate's effect on diabetic retinopathy outcomes³

In this study, a total of 1151 participants with either mild background retinopathy or maculopathy were randomly assigned to receive 145 mg fenofibrate or placebo either daily or every other day in those with impaired kidney function. 27% of participants had type 1 diabetes and 23% had an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². The primary outcome was time to the first occurrence of the composite of developing referable diabetic retinopathy or maculopathy, or treatment for diabetic retinopathy or maculopathy (including intravitreal injection of medication, retinal laser therapy, or vitrectomy) in either eye. The study showed that significant reduction in achieving primary outcome with fenofibrate compared with Placebo (hazard ratio 0.73, p = .006). The occurrence of any retinopathy or maculopathy progression was also significantly less common with fenofibrate, 32.1% versus 40.2% with placebo (hazard ratio [HR], 0.74), as was referral for treatment, 18.6% versus 25.9% with placebo (HR, 0.66). Significant reduction in developing macular oedema was also observed with fenofibtrate (HR, 0.50). No differences was observed between the two groups in visual function, quality of life, or visual acuity. Results were similar for participants with type 1 and type 2 diabetes, and those with normal versus impaired renal function.

Reassuringly, but perhaps unsurprisingly given that fenofibrate has been used widely in clinical practice, no safety concerns was observed. As anticipated, slight reduction in eGFR was observed in the fenofibrate group but this is reversible. It would be interesting to know if this mild reduction in eGFR would translate to long term renal protection, as was observed with SGLT2i and ACE-I therapy. Whether evidence derived from this work would translate to a change in routine practice especially within the ophthalmology circle remains clear. Among physician involved in managing people with type 2 diabetes a low threshold to start fenofibrate should be set especially among patients with diabetic eye diseases.