Abstract

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 x2 = 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 x2 = 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 x2 = 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.

Competing Interest Statement

The authors have declared no competing interest.

Funding Statement

The authors received no financial support for the research, authorship, or publication of this article. No external funding, grants, or in-kind support were obtained for this study.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Not Applicable

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

This study was conducted using deidentified patient data from the TriNetX Global Collaborative Network. Per the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule 164.514(b)(1), a qualified expert determined that the use of these data is exempt from institutional review board (IRB) oversight. No patient identifiers were accessed, and all analyses complied with relevant ethical guidelines.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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Data Availability

The data that support the findings of this study are derived from the TriNetX Global Collaborative Network, which contains de-identified patient information from participating healthcare organizations. Due to data use agreements, the raw data are not publicly available. Access to the TriNetX platform and its datasets can be obtained by qualified researchers through a request to TriNetX (https://www.trinetx.com), subject to institutional approval and data sharing policies.

Non-standard Abbreviations and AcronymsDRDiabetic retinopathyT2DMType 2 Diabetes MellitusNPDRnonproliferative diabetic retinopathyVHvitreous hemorrhageNVneovascularizationTRDtractional retinal detachmentNVGneovascular glaucomaPPVpars plana vitrectomyHMG-CoA3-Hydroxy-3-Methylglutaryl-Coenzyme APPAR-αPeroxisome proliferator-activated receptor alphaHCOshealthcare organizationswet AMDexudative age-related macular degenerationLLDlipid-lower drugPRPpanretinal, photocoagulationPDRproliferative diabetic retinopathyASTaspartate aminotransferaseALTalanine aminotransferaseAKIacute kidney injuryRRrisk ratioCIconfidence intervalsHRHazard ratios