| Outcome Measures: |
Primary: eGFR at the end of the wash-out period following the treatment period, eGFR at the end of the 8-week drug washout period following the 3-year treatment period, estimated from Central Lab serum creatinine and cystatin C using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and adjusted by its baseline value. Baseline and end-of-washout eGFRs will be considered as the average of two eGFR values taken on two separate days before randomization (V2 and V4) and after the washout (V18 and V19), respectively., End of the 2-month wash-out period following the 3-year treatment period (weeks 162 and 164) | Secondary: Time to ≥40% eGFR decline from baseline, kidney failure , or death from renal causes, Time from randomization to 1. sustained ≥40% eGFR decline (based on eGFR estimated from serum creatinine and cystatin C using the 2021 CKD-EPI equation) confirmed after 30 days; 2. kidney failure, defined by eGFR ≤10ml/min/ 1.73m2 confirmed after 30 days or occurring within 30 days prior to death, or initiation of maintenance kidney replacement therapy; or 3. death from kidney-related causes. If an eGFR value meeting the above criteria is observed at the last study visit or immediately before a participant is lost to follow-up or withdraws from the study, no confirmation of this value will be necessary., Up to the end of the 2-month wash-out period following the 3-year treatment period (week 0 to 164) | Other: eGFR at the end of the 3-yr treatment period, eGFR at the end of the 3-yr treatment period (before the washout period) adjusted for the baseline value, End of the 3-year treatment period (week 156)|Time to fatal or non-fatal cardiovascular disease (CVD) events, Time to fatal or non-fatal CVD events (CV death, non-fatal myocardial infarction, non-fatal stroke, or coronary, carotid, or peripheral revascularization procedures), Up to the end of the 2-month wash-out period following the 3-year treatment period (week 0 to 164)|Time to hospitalization or urgent visit for heart failure or CV death, Time to hospitalization or urgent visit for heart failure or death for cardiovascular causes, Up to the end of the 2-month wash-out period following the 3-year treatment period (week 0 to 164)|Time to hospitalization for heart failure, Time to hospitalization for heart failure, Up to the end of the 2-month wash-out period following the 3-year treatment period (week 0 to 164)|B-type natriuretic peptide (NTproBNP) serum levels at the end of the drug washout, Serum levels of NTproBNP at the end of the 8-week drug washout, adjusted for its baseline value, End of the 2-month wash-out period following the 3-year treatment period (week 164)|High-sensitivity cardiac troponin (hs-cTnT) serum levels at the end of the drug washout, Serum levels of hs-cTnT at the end of the 8-week drug washout, adjusted for its baseline value, End of the 2-month wash-out period following the 3-year treatment period (week 164)|NTproBNP serum levels at the end of the treatment period, Serum levels of B-type natriuretic peptide (NTproBNP) at the end of the 3-year treatment period, adjusted for its baseline value, End of the 3-year treatment period (week 156)|hs-cTnT serum levels at the end of the treatment period, Serum levels of high-sensitivity cardiac troponin (hs-cTnT ) at the end of the 3-year treatment period, adjusted for its baseline value, End of the 3-year treatment period (week 156)|Mean blood HbA1c levels during the treatment period, Mean HbA1c during the 3-year treatment period, Weeks 0, 2, 8, 16, 28, 44, 60, 76, 92, 108, 124, 140 156 (from baseline to the end of the treatment period)|Mean blood glucose levels during the treatment period, Mean blood glucose from continuous glucose monitoring during the 3-year treatment period, Weeks 2, 8, 16, 28, 44, 60, 76, 92, 108, 124, 140 156 (from baseline to the end of the treatment period)|Mean GMI during the treatment period, Mean glucose management indicator (GMI) from continuous glucose monitoring during the 3-year treatment period, Weeks 2, 8, 16, 28, 44, 60, 76, 92, 108, 124, 140 156 (from baseline to the end of the treatment period)|Mean time in range (TIR) during the treatment period, Mean time with blood glucose in the 70 to 180 mg /dl range from continuous glucose monitoring during the 3-year treatment period, Weeks 2, 8, 16, 28, 44, 60, 76, 92, 108, 124, 140 156 (from baseline to the end of the treatment period)|Mean time below range 70 (TBR70) during the treatment period, Mean time with blood glucose below 70 mg/dl from continuous glucose monitoring during the 3-year treatment period, Weeks 2, 8, 16, 28, 44, 60, 76, 92, 108, 124, 140 156 (from baseline to the end of the treatment period)|Mean time below range 54 (TBR54) during the treatment period, Mean time with blood glucose below 54 mg/dl from continuous glucose monitoring during the 3-year treatment period, Weeks 2, 8, 16, 28, 44, 60, 76, 92, 108, 124, 140 156 (from baseline to the end of the treatment period)|Mean time above range 180 (TAR180) during the treatment period, Mean time with blood glucose above 180 mg/dl from continuous glucose monitoring during the 3-year treatment period, Weeks 2, 8, 16, 28, 44, 60, 76, 92, 108, 124, 140 156 (from baseline to the end of the treatment period)|Mean time above range 250 (TAR250) during the treatment period, Mean time with blood glucose above 250 mg/dl from continuous glucose monitoring during the 3-year treatment period, Weeks 2, 8, 16, 28, 44, 60, 76, 92, 108, 124, 140 156 (from baseline to the end of the treatment period)|Mean Glucose CV during the treatment period, Mean blood glucose coefficient of variation (CV) from continuous glucose monitoring during the 3-year treatment period, Weeks 2, 8, 16, 28, 44, 60, 76, 92, 108, 124, 140 156 (from baseline to the end of the treatment period)|Mean MAGE during the treatment period, Mean amplitude of glycemic excursions (MAGE) from continuous glucose monitoring during the 3-year treatment period, Weeks 2, 8, 16, 28, 44, 60, 76, 92, 108, 124, 140 156 (from baseline to the end of the treatment period)|Mean GRI during the treatment period, Mean glycemic risk index (GRI) from continuous glucose monitoring during the 3-year treatment period, Weeks 2, 8, 16, 28, 44, 60, 76, 92, 108, 124, 140 156 (from baseline to the end of the treatment period)|Mean total daily insulin dose during the treatment period, Mean total daily insulin dose (TDD, units/kg) during the 3-year treatment period, Weeks 2, 8, 16, 28, 44, 60, 76, 92, 108, 124, 140 156 (from baseline to the end of the treatment period)|Urinary albumin excretion rate change from baseline equal to or more negative than -30% at the end of treatment, Urinary albumin excretion rate (UAER, timed overnight collection) reduction from baseline ≥30% at the end of treatment;, End of treatment period (Week 156).|Urinary albumin excretion rate change from baseline equal to or more negative than -30% at the end of the washout period, Urinary albumin excretion rate (UAER) reduction from baseline ≥30% at the end of the 8-week washout period following the 3-year treatment period;, End of the 2-month wash-out period following the 3-year treatment period (week 164)|eGFR slope during the treatment period, eGFR slope from baseline to the end of the 3-yr treatment period (before the washout period), kidney failure, death, or study discontinuation, whichever occurs first, Weeks 0, 2, 8, 16, 28, 44, 60, 76, 92, 108, 124, 140 156 (from baseline to the end of the treatment period)
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| Locations: |
Stanford University Medical Center, Stanford, California, 94305, United States|Barbara Davis Center / University of Colorado Denver, Aurora, Colorado, 80045, United States|Northwestern University Feinberg School of Medicine, Chicago, Illinois, 60611, United States|Joslin Diabetes Center, Boston, Massachusetts, 02215, United States|Washington University, Saint Louis, Missouri, 63110, United States|Albert Einstein College of Medicine / Montefiore Medical Center, Bronx, New York, 10461, United States|SUNY Upstate Medical University, Syracuse, New York, 13210, United States|Cleveland Clinic Foundation, Cleveland, Ohio, 44195, United States|Oregon Health and Science University, Portland, Oregon, 97239, United States|University of Texas Southwestern, Dallas, Texas, 75390, United States|University of Washington, Seattle, Washington, 98105, United States|Providence Sacred Heart Medical Center, Spokane, Washington, 99204, United States|Unversity of Calgary, Calgary, Alberta, T2T 5C7, Canada|Alberta Diabetes Institute, Edmonton, Alberta, T6G 2E1, Canada|St. Paul's Hospital, Vancouver, British Columbia, V6Z 1Y6, Canada|LMC Diabetes and Endocrinology, Toronto, Ontario, M4G 3E8, Canada|Toronto General Hospital, Toronto, Ontario, M5G 2N2, Canada|Institut de Recherches Cliniques de Montréal, Montreal, Quebec, H2W 1R7, Canada
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