Effect of systemic fibrates on diabetic retinopathy prevention and progression: A comprehensive systematic review and meta-analysis.

Diabetic retinopathy is a leading cause of vision loss in adults with diabetes, and the role of systemic fibrate therapy in its prevention and progression remains debated. We performed a systematic review and meta-analysis to evaluate the effect of fibrates on diabetic retinopathy development and progression, distinguishing randomized from non-randomized evidence. We searched PubMed, Scopus, and Web of Science from inception to August, 2025, and included 31 studies (17 development, 15 progression). Trials enrolling mixed populations were extracted by baseline retinopathy status. Random-effects pooling of 2 randomized trials showed no evidence of a benefit of fenofibrate for incident diabetic retinopathy (odds ratio 1.00, 95% confidence interval 0.70-1.43; low certainty). This estimate is imprecise and cannot exclude a modest protective or harmful effect. Five randomized trials in patients with established disease showed reduced overall progression (odds ratio 0.56, 95% confidence interval 0.42-0.74; moderate certainty) and reduced progression to diabetic macular edema (odds ratio 0.52, 95% confidence interval 0.36-0.74; moderate certainty). Adjusted estimates from non-randomized studies were directionally consistent. These findings support a stage-specific role for fenofibrate in patients with established diabetic retinopathy, particularly to reduce progression to diabetic macular edema, while the evidence for primary prevention remains inconclusive.