Fenofibrate was associated with a reduced risk of progression to vision-threatening forms of diabetic retinopathy in a new large database study.

“The possibility that an oral medication originally used for a different disease may be beneficial for the management of diabetic eye disease is exciting,” writes Robert N. Frank, MD, emeritus professor of ophthalmology at Wayne State University in Detroit, Michigan, in an accompanying editorial to the study published in JAMA Ophthalmology.

The oral drug typically prescribed to lower lipids is also being studied in a number of ongoing clinical trials for the prevention of worsening of diabetic retinopathy, and was approved for that indication in Australia back in 2013.

Two small trials, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Eye study and Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, have already shown a reduction in vision-threatening diabetic retinopathy with fenofibrate.

But the results of these previous studies were somewhat mixed in terms of overall progression of diabetic retinopathy, and guidelines for the drug’s use for this indication have not been consistent across professional societies. The American Academy of Ophthalmology preferred practice pattern for diabetic retinopathy does not comment on fenofibrate use, whereas the American Diabetes Association position statement argues for a collaborative approach to fenofibrate use.

Study Details

To further elucidate the relationship between fenofibrate and diabetic retinopathy, Elana Meer, a researcher at the University of Pennsylvania in Philadelphia, and colleagues, analyzed data from the Optum Clinformatics Data Mart Database of deidentified medical claims for the current study.

In total, 150,252 people had nonproliferative diabetic retinopathy at baseline, of whom 5835 were taking fenofibrate to control their cholesterol and 144,417 were not.

Researchers adjusted for the following covariates: nonproliferative diabetic retinopathy severity, age, sex, race, education, income, geographic location, index year, statin use, insulin use, hypertension diagnosis, drug use, hypercholesterolemia, ischemic heart disease, chronic heart disease, ischemic stroke, chronic liver disease, peripheral vascular disease, any malignancy, blood disorder/cancer, diabetes complications severity index, A1c, anemia, and estimated glomerular filtration rate.

They then calculated the hazard ratio (HR) of progression to more severe stages of diabetic retinopathy. Compared with those not taking fenofibrate, those taking the drug had an 8% lower risk of vision-threatening disease (HR, 0.92; 95% CI, 0.87 – 0.98; P = .01).

Patients taking fenofibrate also had a 24% reduced risk of proliferative disease (HR, 0.76; 95% CI, 0.64 – 0.90; P = .001).

However, in contrast to results of the FIELD study, patients in the current study did not have a significantly reduced risk of diabetic macular edema (HR, 0.96; 95% CI, 0.90 – 1.03; P = .27).

“Our analysis found that fenofibrate use was associated with a lower risk of progression to vision-threatening diabetic retinopathy, but that association seemed to be solely driven by a reduction in proliferative diabetic retinopathy because no association was seen with diabetic macular edema,” note Meer and colleagues.

The study was funded by the National Institutes of Health, University of Pennsylvania, Research to Prevent Blindness, and Paul and Evanina Mackall Foundation. A study author has reported a financial relationship with EyePoint Pharmaceuticals. Meer and Frank have reported no relevant financial relationships.

JAMA Ophthalmol. Published online April 7, 2022. Article, Editorial

Laird Harrison writes about science, health, and culture. His work has appeared in national magazines, in newspapers, on public radio, and on websites. He is at work on a novel about alternate realities in physics. Harrison teaches writing at the Writers Grotto. Visit him at www.lairdharrison.com or follow him on Twitter: @LairdH

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