Fenofibrate Cuts Diabetic Retinopathy Risk by 27%: LENS Trial

A groundbreaking trial presented for the first time at the ADA 2024 demonstrated that Fenofibrate significantly reduces the progression of diabetic retinopathy.

The LENS trial conducted across multiple centers is the first of its kind large scale trial specifically designed to investigate the effect of Fenofibrate on eye outcomes in people with early diabetic retinopathy.

This trial enrolled 1151 participants who were randomly assigned to receive 145 mg fenofibrate tablets or placebo. The primary outcome was a composite of developing referable diabetic retinopathy or maculopathy (based on Scotland’s Diabetic Eye Screening grading scheme) or treatment (intravitreal injection, retinal laser, vitrectomy) for retinopathy or maculopathy. The trial findings have been published in the latest issue of NEJM Evidence.

Over a median follow-up of 4.0 years, 131 participants (22.7%) in the fenofibrate group and 168 participants (29.2%) in the placebo group progressed to referable diabetic retinopathy or maculopathy, or required treatment (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.58 to 0.91; P=0.006). (Refer to Figure 1)

The occurrence of any retinopathy or maculopathy progression was also significantly less common with fenofibrate, 32.1% vs 40.2% with placebo (HR, 0.74). A comparable proportional reduction was noted for referable maculopathy, affecting 107 participants (18.6%) in the fenofibrate group and 149 participants (25.9%) in the placebo group (HR, 0.66). Macular edema occurred in 3.8% with fenofibrate vs in the 7.5% placebo group, which is also significant (HR, 0.50).

Allocation to fenofibrate, compared with placebo, had no effect on visual function, quality of life, or visual acuity

Figure 1: Referable Diabetic Retinopathy or Maculopathy, or Treatment for Diabetic Retinopathy or Maculopathy.

Shown are the results of the primary composite outcome of referable diabetic retinopathy or maculopathy, or treatment thereof, with intravitreal injection of medication, retinal laser therapy, or vitrectomy. The inset graph shows the same data on an expanded y-axis. The primary outcome occurred in 131 participants (22.7%) in the fenofibrate group and in 168 participants (29.2%) in the placebo group, representing 65 fewer primary outcome events per 1000 participants in the fenofibrate group than in the placebo group over a median of 4.0 years of follow-up.

Safety: No Major Concerns:

There was no difference between groups in major cardiovascular events or nontraumatic lower limb amputations and no effect on urine albumin: creatinine ratio. Total and non-HDL cholesterol were slightly lower, while triglyceride levels were a significant 13.7% lower with fenofibrate. The eGFR was 7.9 (95% CI, 6.8 to 9.1) ml/min/1.73 m2 lower in the fenofibrate group compared with the placebo group.

Retinal imaging substudies from cardiovascular outcome trial i.e. the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) trial and the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial have associated fenofibrate use with improvements in diabetic retinopathy.

In summary, for participants with early diabetic retinal changes, fenofibrate treatment resulted in a reduction in the progression of diabetic retinopathy compared to placebo.

Reference: David Preiss, Jennifer Logue, Emily Sammons, Mohammed Zayed, Jonathan Emberson, Rachel Wade,Karl Wallendszus, Will Stevens, Rosanna Cretney, Simon Harding, Graham Leese, Gemma Currie, and Jane Armitage.Effect of Fenofibrate on Progression of Diabetic Retinopathy. NEJM Evidence June 2024.DOI: 10.1056/EVIDoa2400179