Victoria Adrian, PharmD; M Health Fairview
Background: Diabetic retinopathy is a microvascular complication of diabetes that occurs when blood vessels in the retina are damaged by high blood glucose levels. This condition can lead to irreversible vision changes including blurred vision, floaters, or vision loss. Current strategies to slow the progression of diabetic retinopathy include maintaining glycemic control and annual eye exams. Fenofibrate, a peroxisome proliferator-activated receptor alpha agonist (PPAR-alpha agonist), is traditionally used to treat hyperlipidemia and hypertriglyceridemia. In the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) trial, fenofibrate therapy was shown to reduce the risk of proliferative retinopathy or macular edema over five years as a tertiary outcome.
Objective: The purpose of the LENS (Lowering Events in Non-Proliferative Retinopathy in Scotland) trial was to evaluate whether oral fenofibrate affects the progression of diabetic retinopathy.
Study Design: The LENS trial was a double-blind, parallel-group, randomized controlled trial conducted in Scotland from September 2018 through July 2021. The study required participants to be ≥18 years of age, diagnosed with non-referable diabetic retinopathy or maculopathy, and have an eGFR ≥40 mL/min/1.73 m2. Participants were randomly assigned to receive either placebo or oral fenofibrate 145mg with the dosing regimen chosen based on the eGFR measure at randomization assessment (eGFR ≥60 mL/min/1.73 m2 was assigned fenofibrate 145 mg daily; eGFR 30-59 mL/min/1.73 m2 was assigned fenofibrate every other day). If eGFR changed during the trial, the dosing regimen was adjusted accordingly. Each participant had an initial single macula-centered 45-degree digital retinal color photograph taken of each eye. Each eye was graded for the severity of retinopathy or maculopathy using the NHS Scotland diabetes eye screening (DES) program grading scheme. The primary outcome was time to first occurrence of the composite of developing referable diabetic retinopathy or maculopathy in either eye.
Results: A total of 1,151 participants underwent randomization with complete data available for 1,149 participants at the end of the trial. The median age of participants was 61 years, 26% had type 1 diabetes, and the average HbA1c was 8.2%. Ninety-eight percent of participants who underwent randomization had mild background retinopathy and 10% had observable diabetic maculopathy. Significantly fewer participants in the fenofibrate group experienced the primary outcome compared to the placebo group. The primary outcome occurred in 22.7% (131/576) of the fenofibrate treatment group and 29.2% (168/575) of the placebo group (hazard ratio, 0.73; 95% CI, 0.58 to 0.91; P = 0.006; number needed to treat = 16) over a median of 4 years. Progression of retinopathy or maculopathy occurred in 32.1% (185/576) of the fenofibrate group and 40.2% (231/575) of the placebo group (hazard ratio, 0.74; 95% CI, 0.61 to 0.90). There was no difference between the two treatment groups noted for visual function, quality of life, or visual acuity. There was also no difference in cardiovascular complication rates or serious adverse events between the two groups. However, fenofibrate therapy led to an average reduction in eGFR of 8 mL/min/1.73 m2.
Conclusion: This trial concluded that fenofibrate therapy results in a statistically significant reduction in the risk of diabetic retinopathy progression compared to placebo over several years.
Key Points: The LENS trial data may support the early use of fenofibrate in patients with diabetes to reduce the risk of diabetic retinopathy or maculopathy progression. Patients receiving fenofibrate treatment had a 27% lower risk of diabetic retinopathy progression compared to those receiving placebo.
References:
- ElSayed NA, Aleppo G, Bannuru RR, et al. 12. Retinopathy, Neuropathy, and Foot Care: Standards of Care in Diabetes—2024. Diabetes Care. 2023;47(Supplement_1):S231-S243. doi:10.2337/dc24-s012
- Preiss D, Logue J, Sammons E, et al. Effect of fenofibrate on progression of diabetic retinopathy. NEJM Evidence. June 2024. doi:10.1056/evidoa2400179