| Outcome Measures: |
Primary: Occurrence of clinical significant retinopathy progression., Comprising 2-step progression of ETDRS score (to at least moderately severe grade), clinically significant macular oedema, need for laser surgery, need for intraocular anti-VEGF or corticosteroid therapy or vitrectomy, adjudicated to be for diabetic retinopathy (DR), As reported throughout the study and/or annual eye assessment post-randomisation | Secondary: The individual components of the primary endpoint, Clinically significant retinopathy progression, 2-step progression of ETDRS score, At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).|Occurrence of clinically significant macula oedema (CSME)., Occurrence of clinically significant macula oedema (CSME) per standard ophthalmological assessment or laser therapy., As reported throughout the study|Need for laser surgery for DR, Need for laser surgery for DR, As reported throughout the study|Need for intraocular anti-VEGF or corticosteroid injection or vitrectomy, Need for intraocular anti-VEGF or corticosteroid injection or vitrectomy for DR, As reported throughout the study|Visual acuity., Visual acuity using ETDRS/LogMar or Snellen Chart, At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).|Macular volume and thickness, Macular volume and thickness by Optical Coherence Tomography (OCT), At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).|Albuminuria., Albuminuria measured as urinary albumin:creatinine ratio., At baseline, 12 m post-randomisation, 24 m post-randomisation, the end of study visit (which is on average 36 months post-randomisation) and wash-out visit.|Estimated glomerular filtration rate., Estimated glomerular filtration rate using Modification of Diet in Renal Disease (MDRD) formula., At study completion and washout visit|Peripheral neuropathy status, Peripheral neuropathy status assessed by temperature \& vibration sensation and monofilament test., At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).|Autonomic neuropathy., Autonomic neuropathy (QTc and R-R intervals) on annual ECGs., At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit (which is on average 36 months post-randomisation).|Total cardiovascular events., Total cardiovascular events including myocardial infarction, stroke, sudden cardiac death, hospitalisation for acute coronary syndrome or any revascularisation events., As reported throughout the study.|Frequency of foot ulcer and non-traumatic amputation., Foot ulcer and/or non-traumatic amputation are reported by site during the study., As reported throughout the study | Other: Lipid and lipoprotein levels, Lipid and lipoprotein levels, At baseline and end of study|Biomarkers and molecular markers, Markers of inflammation, glycation and oxidative stress, angiogenesis and adipocyte function, and molecular markers, as change from baseline with study treatment, At baseline and end of study|Quality of Life questionnaire, Quality of Life questionnaire completed by participants annually, At baseline, 12 m post-randomisation, 24 m post-randomisation and the end of study visit
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| Locations: |
Canberra Hospital, Garran, Australian Capital Territory, 2605, Australia|Royal Prince Alfred Hospital, Camperdown, New South Wales, 2050, Australia|Concord Repatriation General Hospital, Concord, New South Wales, 2139, Australia|Garvan Institute of Medical Research, Darlinghurst, New South Wales, 2010, Australia|Retina Associates - South West Retina, Liverpool, New South Wales, 2170, Australia|Hunter Diabetes Centre, Merewether, New South Wales, 2291, Australia|Prince of Wales Hospital, Randwick, New South Wales, 2032, Australia|Royal North Shore Hospital, Saint Leonards, New South Wales, 2065, Australia|Cairns Hospital, Cairns, Queensland, 4870, Australia|Mater Adult Hospital, South Brisbane, Queensland, 4101, Australia|Princess Alexandra Hospital, Woolloongabba, Queensland, 4102, Australia|Royal Adelaide Hospital, Adelaide, South Australia, 5000, Australia|Southern Adelaide Diabetes and Endocrine Services, Oaklands Park, South Australia, 5046, Australia|University Hospital Geelong, Geelong, Victoria, 3220, Australia|Heidelberg Repatriation Hospital, Heidelberg, Victoria, 3081, Australia|Baker Heart and Diabetes Institute, Melbourne, Victoria, 3004, Australia|St Vincent's Hospital Melbourne, Melbourne, Victoria, 3065, Australia|The Royal Melbourne Hospital, Parkville, Victoria, 3050, Australia|Sunshine Hospital, St Albans, Victoria, 3021, Australia|Fremantle Hospital, Fremantle, Western Australia, 6160, Australia|Prince of Wales Hospital, Shatin, New Territories, Hong Kong|Auckland Diabetes Centre, Auckland, 1051, New Zealand|Christchurch Hospital, Christchurch, 8011, New Zealand|Belfast Health and Social Care Trust, Belfast, BT12 6BA, United Kingdom
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