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Brief Report
April 7, 2022

Association of Fenofibrate Use and the Risk of Progression to Vision-Threatening Diabetic Retinopathy

Author Affiliations
  • 1Scheie Eye Institute, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia
  • 2Center for Preventative Ophthalmology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia
  • 3Center for Clinical Epidemiology and Biostatistics, Department of Biostatistics & Epidemiology, University of Pennsylvania Perelman School of Medicine, Philadelphia
  • 4Leonard Davis Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia
JAMA Ophthalmol. 2022;140(5):529-532. doi:10.1001/jamaophthalmol.2022.0633
Key Points

Question  What is the association of fenofibrates with progression of nonproliferative diabetic retinopathy to vision-threatening diabetic retinopathy?

Findings  In this cohort study of 5835 fenofibrate users and 144 417 fenofibrate nonusers, use of fenofibrates was not associated with risk of diabetic macular edema alone. However, it was found to be associated with a decreased risk of proliferative diabetic retinopathy and vision-threatening diabetic retinopathy (a composite outcome of either proliferative diabetic retinopathy or diabetic macular edema).

Meaning  In addition to dyslipidemic effects, use of fenofibrates in patients with diabetic retinopathy may reduce their risk of progression to visually threatening forms of disease.


Importance  Diabetic retinopathy (DR) may progress from nonproliferative DR (NPDR) to vision-threatening DR (VTDR). Studies have investigated fenofibrate use as a protective measure with conflicting results, and fenofibrate is not typically considered by ophthalmologists in the management of DR currently.

Objective  To assess the association between fenofibrate use and the progression from NPDR to VTDR, proliferative DR (PDR), or diabetic macular edema (DME).

Design, Setting, and Participants  This multicenter cohort study used medical claims data from a large US insurer. Cohorts were created from all patients with NPDR 18 years or older who had laboratory values from January 1, 2002, to June 30, 2019. Exclusion criteria consisted of any previous diagnosis of PDR, DME, proliferative vitreoretinopathy, or treatment used in the care of VTDR. Patients were also excluded if they had a diagnosis of VTDR within 2 years of insurance plan entry, regardless of when NPDR was first noted in the plan.

Exposures  Fenofibrate use.

Main Outcomes and Measures  The main outcomes were a new diagnosis of VTDR (a composite outcome of either PDR or DME) or DME and PDR individually. A time-updating model for all covariates was used in multivariate Cox proportional hazard regression to determine hazards of progressing to an outcome. Additional covariates included NPDR severity scale, systemic illnesses, demographics, kidney function (based on estimated glomerular filtration rate level), hemoglobin A1c, hemoglobin, and insulin use.

Results  A total of 5835 fenofibrate users with NPDR at baseline (mean [SD] age, 65.3 [10.4] years; 3564 [61.1%] male; 3024 [51.8%] White) and 144 417 fenofibrate nonusers (mean [SD] age, 65.7 [12.3] years; 73 587 [51.0%] male; 67 023 [46.4%] White) were included for analysis. Of these, 27 325 (18.2%) progressed to VTDR, 4086 (2.71%) progressed to PDR, and 22 750 (15.1%) progressed to DME. After controlling for all covariates, Cox model results showed fenofibrates to be associated with a decreased risk of VTDR (hazard ratio, 0.92 [95% CI, 0.87-0.98]; P = .01) and PDR (hazard ratio, 0.76 [95% CI, 0.64-0.90]; P = .001) but not DME (hazard ratio, 0.96 [95% CI, 0.90-1.03]; P = .27).

Conclusions and Relevance  In this study, fenofibrate use was associated with a decreased risk of PDR and VTDR but not DME alone. These findings support the rationale for additional clinical trials to determine if these associations may be representative of a causal relationship between fenofibrate use and reduced risk of PDR or VTDR.

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