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.