Associations between fenofibrate use and sight-threatening diabetic retinopathy in type 2 diabetes: UK real-world evidence.

OBJECTIVE: Half of individuals with type 2 diabetes (T2D) also experience dyslipidaemia. In a phase IV clinical trial, fenofibrate was shown to reduce the risk of referable diabetic retinopathy (DR) comparing to placebo in people with background diabetic retinopathy (BDR). We aimed to generate comprehensive real-world evidence on the effects of fenofibrate on the risk of sight-threatening diabetic retinopathy (STDR) in individuals with T2D, compared with statins. METHODS: This propensity score-matched, prevalent new-user comparative effectiveness trial emulation study included adults (≥18 years) with T2D, receiving either statins or fenofibrate, as recorded in Clinical Practice Research Datalink (a UK primary care database) from 1 January 2000 to 30 June 2022. The primary outcome was incident STDR. After propensity score matching, competing risk Cox proportional hazard regression models were used to estimate the crude and adjusted hazard ratios (aHR) in both intention-to-treat (ITT) and per-protocol (PP) analyses. RESULTS: Data from 16,337 fenofibrate new users and their matched 25,764 statin users were included in this study. Participants were followed up for up to 12 years. Fenofibrate use was associated with a reduced risk of developing STDR (aHR: ITT 0.87, 95% CI 0.82-0.93; PP 0.80, 0.74-0.87) in comparison with the statin group. The results were consistent across sensitivity analysis and subgroups based on age, sex, ethnicity, and lipid levels. However, the protective effect was not observed in South Asians. CONCLUSIONS: Fenofibrate use was associated with a reduced risk of STDR in individuals with T2D in the real-world clinical practice. These fundings suggest that fenofibrate could be considered as a DR preventive therapy for individuals with T2D.