LENS Trial: Fenofibrate Significantly Reduced Progression of Diabetic Retinopathy vs Placebo.

By M Cecilia Bahit, MD on

Findings from cardiovascular trials suggested that fenofibrate therapy may reduce the progression of diabetic retinopathy.

– The LENS (Lowering Events in Non-proliferative retinopathy in Scotland) was a pragmatic trial to assess the effect of fenofibrate on the progression of retinopathy vs placebo conducted in Scotland.

-Fenofibrate was associated with a 27% reduction in the progression of diabetic retinopathy compared to placebo.

Diabetic retinopathy is a common complication of diabetes and a leading cause of vision loss worldwide. Treatments for advanced disease are expensive, require expertise to deliver, and sometimes are ineffective. This is why diabetic retinal screening is recommended to identify people at risk of this condition. Fenofibrate is an orally administered peroxisome proliferator-activated receptor alpha agonist that reduces circulating triglycerides and non–high-density lipoprotein (HDL) cholesterol levels. Findings from the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) and the ACCORD (Action to Control Cardiovascular Risk in Diabetes)trials suggest that fenofibrate may reduce diabetic retinopathy.  The LENS (Lowering Events in Non-proliferative retinopathy in Scotland) trial (Funded by the National Institute for Health and Care Research; ClinicalTrials.gov number, NCT03439345;ISRCTN number, ISRCTN15073006.)a pragmatic, national, randomized, parallel-group, double-blind, placebo-controlled clinical trial of fenofibrate set within a national retinal screening program — was designed to assess its effect on progression of retinopathy in people with early diabetic eye disease. The results were presented at a symposium during the American Diabetes Association’s (ADA) 84th Scientific Sessions in Orlando, FL, and were simultaneously published in NEJM Evidence.

The study recruited and followed adults with nonreferable diabetic retinopathy or maculopathy using the national Diabetic Eye Screening (DES) program in Scotland. Patients were randomly assigned to receive 145-mg fenofibrate tablets or placebo (taken daily or, in those with impaired renal function, on alternate days). The primary outcome was a composite of developing referable diabetic retinopathy or maculopathy (based on Scotland’s DES grading scheme) or treatment (intravitreal injection, retinal laser, vitrectomy) for retinopathy or maculopathy.

A total of 1151 participants were included and randomly assigned to treatment. During a median of 4.0 years, progression to referable diabetic retinopathy or maculopathy, or treatment thereof, occurred in 22.7% of patients in the fenofibrate group and 29.2% in the placebo group (hazard ratio, 0.73; 95% confidence interval [CI], 0.58 to 0.91; P=0.006).

The frequencies for any progression of retinopathy or maculopathy were 32.1% vs. 40.2% [hazard ratio, 0.74; 95% CI, 0.61 to 0.90], and for the development of macular edema were 3.8% vs. 7.5% [ hazard ratio, 0.50; 95% CI, 0.30 to 0.84] for the fenofibrate vs placebo groups respectively. Only seventeen (3.0%) patients assigned to fenofibrate and 28 (4.9%) assigned to placebo were given treatment for retinopathy (hazard ratio, 0.58; 95% CI, 0.31 to 1.06). There was no effect on visual function, quality of life, or visual acuity. Trial-averaged Estimated glomerular filtration rate was 7.9 (95% CI, 6.8 to 9.1) ml/min/1.73 m2 lower in participants in the fenofibrate group compared with the placebo group. Serious adverse events occurred in one-third of patients in both treatment arms.

“Diabetic retinopathy remains a leading cause of visual loss and we need simple strategies that can be widely used to reduce the progression of diabetic eye disease,” said Dr. David Preiss, MRCP, FRCPath, PhD, Associate Professor at Oxford Population Health. “Results from the LENS trial suggest that fenofibrate may provide a valuable addition to treat people with diabetic retinopathy.”