2025 AMA Research Challenge – Member Premier Access

October 22, 2025

Virtual only, United States

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Title Comparative Effects of Statins and Fibrates on the Onset of Diabetic Retinopathy in Type 2 Diabetes

Background Diabetic retinopathy (DR) is a common complication of type 2 diabetes mellitus (T2DM) and a leading cause of vision loss in working-age adults. Management often requires invasive, costly procedures to preserve vision and while lipid-lowering drugs (LLDs), particularly statins and fibrates, have shown promise in slowing DR progression, their role in disease onset remains unclear. This study evaluated the association between statin or fibrate therapy and DR onset to assess their prophylactic potential.

Methods This retrospective cohort study used de-identified electronic health records from 152 healthcare organizations via the TriNetX Global Network. Patients with T2DM and no prior ocular complications, diagnosed at least 10 years prior, were assigned to fibrate-only (n = 7,004) or statin-only (n = 463,588) cohorts. Drug exposure required two records: one within 6 months and one at least 1 year after diagnosis. After propensity score matching on demographic characteristics, retinal vascular and non-diabetic retinopathy conditions, and serum HDL, LDL, triglycerides, and HbA1c, each cohort included 6,691 patients. Outcomes included diagnosis of nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), or need for antiVEGF injections or retinal laser. Patients with outcomes prior to cohort entry were excluded.

Results Fibrate therapy was associated with lower risk of DR across all stages: 55.1% reduction in mild NPDR (RR = 0.449; 95% CI: 0.359, 0.561; p < 0.001), 68.7% in moderate (RR = 0.313; 95% CI: 0.202, 0.486; p < 0.001), 65.3% in severe (RR = 0.357; 95% CI: 0.174, 0.735; p < 0.004), and 67.6% in PDR (RR = 0.324; 95% CI: 0.203, 0.517; p < 0.001). Onset was also delayed: mild (log-rank x2 = 25.238; p < 0.001), moderate (log-rank x2 = 17.419; p < 0.001), severe (log-rank x2 = 5.140; p < 0.024), and PDR (log-rank x2 = 15.125; p < 0.001). Fibrate users had a 66.7% reduced risk of retinal laser (RR = 0.333; 95% CI: 0.212, 0.524; p < 0.001) and longer time-to-event (log-rank x2 = 14.372; p < 0.001). No difference was found in antiVEGF injection risk.

Conclusion Fibrate therapy was associated with reduced risk and delayed onset of DR in patients with T2DM compared to statin therapy. These findings support a potential role for fibrates in DR prophylaxis.

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