Effect of fenofibrate on diabetic retinopathy progression: an RCT-Only systematic review and meta-analysis incorporating the LENS trial.

Diabetic retinopathy (DR) causes preventable vision loss, yet treatments remain reactive. Fenofibrate showed ophthalmic benefits in cardiovascular trials, and LENS (2024) expanded the evidence. Under a pre-registered PRISMA 2020 protocol we searched four databases to June 25, 2026 for randomized trials of fenofibrate reporting an ophthalmic outcome in adults with diabetes, applied RoB 2 and GRADE, and pooled dichotomous outcomes as random-effects risk ratios (RR). Ten studies met inclusion criteria: six completed with extractable results and four ongoing; three completed trials contributed to the primary pooled outcome. All enrolled predominantly type 2 diabetes (one trial 26% type 1, no type-specific estimate). For DR progression, three trials (N = 3,756) gave RR 0.77 (95% CI 0.68-0.88;HKSJ 0.60-0.99; I2 0%; moderate certainty), 45 fewer events per 1,000; stratification gave 0.80 (0.68-0.93) for the LENS composite and 0.70 (0.55-0.90) for ETDRS step-based definitions (difference P = 0.37). Need for retinal treatment fell under the conventional model (RR 0.68, 0.57-0.82) but at low certainty: 90.2% of the weight came from one pre-anti-VEGF-era trial and the HKSJ interval crossed the null (0.42-1.11), so this outcome is not firm evidence about contemporary treatment need. No trial found benefit for visual acuity or function (low certainty); macular edema evidence was not combinable (very low certainty). Venous thromboembolism was increased (RR 1.52, 1.12-2.06), an estimate derived entirely from FIELD (103/4,755 vs 68/4,767). In adults with diabetes, predominantly type 2, fenofibrate slows structural DR progression but is not established as vision-preserving.