Primary outcome was a composite of the development of referable diabetic retinopathy or referable maculopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). Referable diabetic retinopathy was defined by the NHS Scotland's grading criteria as any development of R3, R4 or M2 disease. R3 (referable background diabetic retinopathy): any of four or more blot hemorrhages in both inferior and superior hemi-fields, or venous beading, or intraretinal microvascular abnormalities (IRMA); R4 (proliferative diabetic retinopathy): any active new vessels, or vitreous hemorrhage; M2 (referable maculopathy): any blot hemorrhages, or hard exudates within a radius of ≤1 optic disc diameter of the centre of the fovea. Adverse event reports of eye procedures, vitreous haemorrhages and macular oedema were adjudicated by experienced doctors at the Central Co-ordinating Office (CCO), masked to treatment allocation.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence.

Progression of Diabetic Retinopathy/Maculopathy to a referable grade (R3 or R4 or M2) based on the NHS Scotland grading scheme in at least one eye.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence.

Treatment for diabetic retinopathy or maculopathy (including intravitreal injection of medication, retinal laser therapy, or vitrectomy) in either eye.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to first occurrence.

Any progression of diabetic retinopathy or maculopathy across the NHS Scotland retinopathy grading scale. R4 = Proliferative DR, R3 = Referable background DR, R2 = Observable background DR. R1 = Mild background DR, R0 = No DR anywhere (where R4 is the highest severity grade and R0 is the lowest grade); M2 = Referable maculopathy, M1 = Observable maculopathy, M0 = No Maculopathy (where M2 is the highest severity grade and M0 is the lowest grade).

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence

The presence of hard exudates or blot haemorrhages within 1 disc diameter of the macula/fovea

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence

The accumulation of macular fluid as determined by optical coherence tomography (OCT) imaging or on adverse event report

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence

Based on measurement of visual acuity at retinal screening visits. Baseline visual acuity was taken from routine measurement within NHS Scotland's Diabetic Eye Screening programme (using the latest value within 18 months of randomisation). Visual acuity after randomisation was obtained by averaging available results for a participant. Conversion from Snellen to LogMAR was applied where necessary. This analysis is based on the better eye: if only 1 eye with results, analyse that eye; if 2 eyes, use eye with better acuity; if identical acuity in both eyes, use the right eye. LogMAR typically ranges from -0.3 (20/10 vision on the Snellen chart) to 1 (20/200 vision). Lower scores indicate better vision.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on trial-averaged visual acuity.

Visual function is based on the Visual Function Questionnaire-25. Visual function was defined by the composite score derived from the VFQ-25. VFQ-25 data were collected at the screening visit, after two years and at the end of the study. Results from two years and end-of-study were averaged to provide a trial-averaged result for a participant. The VFQ-25 composite score ranges from 0 to 100, where higher scores indicate better visual function. It is calculated by averaging results from up to 11 vision-related sub-scales.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on trial-averaged VFQ-25 Composite Score. Collected at baseline, at approximately 2 years and at the end of the trial.

Quality of life was measured using the EQ-5D instrument, and valued by mapping to the EQ-5D-3L UK value set using the mapping function developed by Hernandez Alava et al. Pharmaco Economics (2022). EQ-5D data were collected at the screening visit, after two years and at the end of the study. Results from two years and end-of-study were averaged to provide a trial-averaged result for a participant. Possible scores range from -0.59 to 1.00, where 1 is the best possible health state and 0 represents a quality of life considered equivalent to death.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on trial-averaged EQ-5D Index Score. Collected at baseline, at approximately 2 years and at the end of the trial.

EQ-5D Visual Analogue Scale data were collected at the screening visit, after two years and at the end of the study. Results from two years and end-of-study were averaged to provide a trial-averaged result for a participant. EQ VAS scores range from 0 to 100, where 100 is the best possible health state.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on trial-averaged EQ-5D Visual Analogue Scale. Collected at baseline, at approximately 2 years and at the end of the trial.

Health economic analysis: cost to the health service over 2 years. This included (i) hospital inpatient and outpatient activity (costed with nationally representative NHS costs); (ii) costs of fenofibrate (based on 200mg NHS cost); (iii) laboratory tests (NHS cost (including nurse/doctor time)); (iv) community prescribed medicines (NHS costs); (v) NHS Scotland retinal screening (published NHS unit costs); (vi) treatment for advanced retinopathy: for relevant participants, application of assumptions regarding usual number of injections from UK cohort study.

Comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo over 2 years

Health economic analysis: Cost-effectiveness (incremental cost per QALY gained). The result is the value of GBP (British Pound) expenditure required to gain 1 quality adjusted life year for fenofibrate therapy vs. standard care. Years gained are presented by arm with 95% credible intervals taken as 2.5th and 97.5th percentile of simulated probabilistic output.

QALY calculated based on quality of life data from EQ-5D questionnaires collected at baseline, at approximately 2 years and at the end of the trial.

Composite primary outcome in prespecified subgroup according to the baseline characteristic: Sex - male. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence

Composite primary outcome in prespecified subgroup according to the baseline characteristic: Sex - female. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence

Composite primary outcome in prespecified subgroup according to the baseline characteristic: Age <60 years. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence

Composite primary outcome in prespecified subgroup according to the baseline characteristic: Age ≥60 years. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence

Composite primary outcome in prespecified subgroup according to the baseline characteristic: Type of Diabetes - type 1 diabetes. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence

Composite primary outcome in prespecified subgroup according to the baseline characteristic: Type 2 and other diabetes. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence

Primary outcome in prespecified subgroup according to the baseline characteristic: Renal function at Randomisation - eGFR <60mL/min/1.73m^2). The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence.

Composite primary outcome in prespecified subgroup according to the baseline characteristic: Renal function at Randomisation - eGFR ≥60mL/min/1.73m^2. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence

Primary outcome in prespecified subgroup according to the baseline characteristic: HbA1c at Screening <70mmol/mol. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence.

Primary outcome in prespecified subgroup according to the baseline characteristic-HbA1c at Screening - ≥70mmol/mol. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence.

Composite primary outcome in prespecified subgroup according to the baseline characteristic - HbA1c at Screening - Unknown. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence.

Composite primary outcome in prespecified subgroup according to the baseline characteristic: Timing of primary outcome - Within first year. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence.

Composite primary outcome in prespecified subgroup according to the baseline characteristic: Timing - After first year. The primary outcome was a composite of the development of referable diabetic retinopathy, or treatment for diabetic retinopathy or maculopathy (including retinal laser therapy, vitrectomy or intravitreal injection of medication). The definition for referable diabetic retinopathy is provided above in '1. Primary Outcome: Number of Participants with Progression to Referable Diabetic Retinopathy or Maculopathy, or Treatment.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence

Based on collection of biochemical data. Urine albumin: creatinine ratio (UACR) results. Urine was collected for measurement of UACR at LENS screening visits wherever possible (baseline results). Post randomization UACR results came from measurements conducted part of routine care. Post randomisation results for a participant were averaged for each participant. Separate values for participants assigned fenofibrate and placebo are reported as geometric mean (95% confidence intervals) and the difference between arms is reported as a percentage difference (95% confidence intervals)

Intention-to-treat comparisons among randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on trial-averaged UACR.

This outcome is a composite of myocardial infarction, stroke, coronary artery revascularisation and peripheral artery revascularisation.

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence.

Composite of any non-traumatic lower limb amputation (defined as minor amputation [distal to the ankle] or major amputation [through or proximal to the ankle]).

Intention-to-treat comparisons among all randomised participants of the effects of allocation to fenofibrate versus placebo during the scheduled treatment period on time to the first occurrence