Outcomes of Fibrate vs Statin Therapy in Patients With Nonproliferative Diabetic Retinopathy and Type 2 Diabetes

Importance Diabetic retinopathy (DR) progression significantly impacts vision and quality of life in patients with Type 2 Diabetes Mellitus (T2DM). Statins and fibrates are commonly prescribed lipid-lowering medications, but their comparative effectiveness in DR progression remains uncertain. Objective To determine whether fibrates reduce the risk of DR progression compared to statins in patients with T2DM and nonproliferative diabetic retinopathy (NPDR). Design, Setting, and Participants Retrospective cohort study using the TriNetX Global Collaborative Network, a multicentered, population-based electronic medical record database. Inclusion criteria consisted of patients diagnosed with T2DM and NPDR 5-20 years prior. Patients were propensity score matched based on demographics and comorbidities. Two cohorts were defined: patients on fibrates but not statins (n = 543), and patients on statins but not fibrates (n = 60,135). After matching, each cohort included 542 patients. Main Outcomes and Measures Primary outcomes: intravitreal antiVEGF injection or retinal laser procedures Secondary outcomes: progression to PDR, vitreous hemorrhage (VH), neovascularization (NV), or tractional retinal detachment (TRD) Tertiary outcomes: neovascular glaucoma (NVG) or pars plana vitrectomy (PPV). Results Fibrate-treated patients had a 57.3% risk reduction in anti-VEGF injection (RR = 0.427; 95% CI: 0.219, 0.830; p < 0.011) and longer time-to-injection (log-rank x 2 = 4.927; p < 0.027). PDR risk was reduced by 59.3% (RR = 0.407; 95% CI: 0.242, 0.684; p < 0.001) with delayed progression (log-rank x 2 = 8.657; p < 0.004). Fibrate use was associated with 72.1% lower instantaneous risk of NGV (HR = 0.279; 95% CI: 0.079, 0.991, p < 0.015) and delayed onset (log-rank x 2 = 4.448, p < 0.036) despite a higher survival probability in the statin group (97.08% vs 96.65%). Fibrates lowered the absolute risk of NV (−0.019; 95% CI: −0.030, −0.007; p < 0.002) but increased risk of TRD (0.018; 95% CI: 0.007, 0.030; p < 0.003); however, neither occurred in the comparison group, limiting statistical power. Conclusions and Relevance Among patients with T2DM and NPDR, fibrates were associated with reduced risk of antiVEGF injection, PDR progression, and NVG onset compared to statins. These findings suggest fibrates may help mitigate DR progression.