Fenofibrate Use May Reduce Progression to Vision-Threatening Diabetic Retinopathy

Brian L. VanderBeek, MD, MPH

New findings suggest fenofibrate use was associated with a decreased risk of progression from non-proliferative diabetic retinopathy (NPDR) to proliferative diabetic retinopathy (PDR) and vision-threatening diabetic retinopathy (VTDR), but not diabetic macular edema (DME) alone.

Additional clinical trials may be necessary to determine if these associations are representative of a causal relationship between fenofibrate use and reduced risk.

“Our positive association for progression to PDR coincides with results of previous clinical trials and adds new information with regards to the impact on DME,” wrote study author Brian L. VanderBeek, MD, MPH, MSCE, Scheie Eye Institute.

Previous research including the ACCORD-EYE study showed reduced progression of diabetic retinopathy severity, but did not address the thresholds of DME or PDR. In contrast, the FIELD study showed reduced laser treatment of DME and PDR with fenofibrate use, but mixed results in the overall progression of diabetic retinopathy.

Accordingly, there is interest in the potential role of fenofibrate in diabetic retinopathy care, with ongoing randomized clinical trials taking place through the DRCR Retina Network.

The current study aimed to further assess the association between fenofibrate use with diabetic retinopathy progression using medical claims of all beneficiaries in a commercial and Medicare administrative database.

Study cohorts were created from all patients with NPDR 18 years or older from who had laboratory values from January 2002 - June 2019. Criteria for exclusion consisted of any previous diagnosis of PDR, DME, proliferative vitreoretinopathy, or treatment used in the care of VTDR.

The main outcomes were identified as a new diagnosis of VTDR or DME and PDR individually, defined by International Classification of Diseases or Current Procedure Terminology codes. Additionally, a time-updating model for all covariates was used in multivariate Cox proportional hazard regression to determine the hazards of progressing to VTDR.

Investigators included a total of 5835 fenofibrate users at baseline with a mean age of 65.3 years (3564 [61.1%] male patients; 3024 [51.8%] White patients) in the analysis. Moreover, they included 144,417 fenofibrate nonusers, with a mean age of 65.7 years (73,587 [51.0%] male; 67,023 [48.4%] White) in the analysis.

In the observation period, data show 27,325 (18.2%) patients progressed to VTDR, 4086 (2.71%) progressed to PDR, and 22,750 (15.1%) progressed to DME.

After controlling for covariates, Cox model results showed the association between fenofibrate and 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).

However, no association was observed on development of DME (hazard ratio, 0.96 [95% CI, 0.90 - 1.03]; P = .27).

“Our findings offer further hope that the DRCR Retina Network clinical trial will prove beneficial for progression to PDR but some concern for those who are hoping for reduction in DME incidence,” VanderBeek concluded.

The study, “Association of Fenofibrate Use and the Risk of Progression to Vision-Threatening Diabetic Retinopathy,” was published in JAMA Ophthalmology.