Fenofibrate for Prevention of DR Worsening


About this study

The purpose of this study is to evaluate the effect of fenofibrate compared with placebo for prevention of diabetic retinopathy (DR) worsening or center-involved diabetic macular edema (CI-DME) with vision loss through 4 years of follow-up in participants with mild to moderately severe non-proliferative DR (NPDR) and no CI-DME at baseline.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • ​​Age ≥ 18 and ≤ 80 years of age.
  • Diagnosis of diabetes mellitus (type 1 or type 2).
  • Both eyes meet the study eye criteria listed below.
  • Able and willing to provide informed consent.
  • Able and willing to wear a continuous glucose monitoring (CGM) device (for United States participants only).
  • Either: (1) both eyes have mild- to- moderately severe NPDR (defined by ETDRS DR severity level 35 to 47) or (2) one eye has mild- to- moderately severe NPDR and the other eye has microaneurysms only (DR severity level 20).
  • Confirmation of DR severity level is required by both the investigator and central Reading Center grading of fundus photographs.
  • Both eyes must have best-corrected E-ETDRS visual acuity letter score ≥79 (approximate Snellen equivalent 20/25 or better).
  • Both eyes must have media clarity, pupillary dilation, and study participant cooperation sufficient to obtain adequate fundus photographs, fluorescein angiogram, and OCT.
  • Investigator must verify accuracy of OCT scan by ensuring it is centered and of adequate quality (including segmentation line placement.

Exclusion Criteria:

  • A condition that, in the opinion of the investigator, would preclude participation in the study (e.g., unstable medical status that may preclude successful completion of follow-up).
  • Initiation of intensive insulin treatment (a pump or multiple daily injections) within 3 months prior to screening or plans to do so in the next 3 months.
  • Participation in an investigational trial that involved treatment within 30 days of screening with any drug that has not received regulatory approval for the indication being studied.
  • Known allergy or hypersensitivity to any component of fenofibrate.
  • Known allergy to fluorescein dye.
  • History of treatment with a prescription fibrate medication (e.g. bezafibrate, fenofibrate, gemfibrozil, fenofibric acid) within 12 months prior to screening or anticipated need for fibrate medication for another indication (e.g. lipid management).
  • Any prior systemic treatment for DME or DR.
  • Decreased renal dysfunction, defined as requiring dialysis or central laboratory eGFR value < 60.
  • Active liver disease, defined as any liver function test > 3 x upper limit of normal based on central laboratory value.
  • Pre-existing symptomatic gallbladder disease including gallstones; however, prior gallbladder removal is not an exclusion.
  • Triglycerides > 400mg/dL on treatment or > 700mg/dL on no treatment based on central laboratory value.
  • Current use of any of the following medications:
    • Coumarin anticoagulants (Coumadin/Warfarin).
    • Immunosuppressants that affect kidney function, such as cyclosporine and tacrolimus.
    • Colchicine (Colcrys).
  • History of severe myalgia requiring discontinuation of lipid lowering treatment.
  • Blood pressure > 160/100 (systolic above 160 or diastolic above 100).
  • HbA1c > 11.0% based on central laboratory value or if lab sample cannot be analyzed, recent result within 3 months.
  • Systemic anti-VEGF or pro-VEGF treatment within 4 months prior to screening or anticipated use during the study.
  • For women of child-bearing potential: pregnant or lactating or intending to become pregnant within the next 4 years.
  • Participant is expecting to move out of the area of the clinical center to an area not covered by another clinical center during the next four years.
  • The following exclusions apply to both eyes:
    • Evidence of definite neovascularization according to the investigator or central Reading Center grading of fluorescein angiography.
    • Includes presence of neovascularization (NV) outside of the 7-modified ETDRS fields on ultra-widefield imaging, which is an exclusion.
  • Current CI-DME based on clinical exam or OCT central subfield thickness (CST), defined as:
    • Zeiss Cirrus: CST ≥ 290 µm in women or ≥ 305 µm in men.
    • Heidelberg Spectralis: CST ≥ 305 µm in women or ≥320 µm in men.
  • Major non-diabetic intraocular pathology that in the opinion of the investigator would substantially and adversely affect visual acuity or lead to ocular neovascularization during the study.
  • Any prior treatment for DME or DR.
  • History of major ocular surgery within prior 4 months or anticipated within the next 6 months following randomization.
  • Anticipated need for intraocular anti-VEGF or PRP in the next 6 months following randomization.
  • History of intraocular anti-VEGF or corticosteroid treatment within the prior year for any indication.
  • Any history of vitrectomy.
  • History of YAG capsulotomy performed within 2 months prior to screening.
  • Aphakia.
  • Evidence of uncontrolled glaucoma (intraocular pressure must be <30, with no more than one topical glaucoma medication, and no documented glaucomatous field loss for the eye to be eligible).

Eligibility last updated 1/21/22. Questions regarding updates should be directed to the study team contact.


Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Andrew Barkmeier, M.D.

Open for enrollment

Contact information:

Hamad Gul

(507) 284-5833


More information


Publications are currently not available

Mayo Clinic Footer