| Outcome Measures: |
Primary: Change in Oral Disposition Index (oDI), The oDI value is the product of total responsivity index and insulin sensitivity. The change in oDI from baseline to 6M on treatment is calculated as the difference between 6M oDI value and baseline oDI value. The oDI measures the ability of beta-cell to respond to a glucose stimulus., Baseline and 6 months|Change in Protein Density Fat Fraction (PDFF), The change in PDFF from baseline to 6M on treatment is calculated as the difference between 6M PDFF value and Baseline PDFF. It provides an accurate, non-invasive, reproducible, quantitative, and precise estimation of liver fat content. The expected changes in MRI-PDFF from baseline to 6M is ≥ 5.8% reduction compared to the placebo group., Baseline and 6 months | Secondary: Change in Oral glucose tolerance test (OGTT) derived biomarkers: oDI, Change in oDI from baseline to 9M after the wash-out period, calculated as the difference between 9M oDI value and baseline oDI value. This is similar to Outcome 1 except measured at 9M., Baseline and 9 months|Change in OGTT derived biomarkers: fasting insulin, Change in fasting insulin calculated as 1/Fasting Insulin \[1/IF\] from baseline to 6M., Baseline and 6 months|Change in OGTT derived biomarkers: fasting insulin, Change in fasting insulin calculated as 1/Fasting Insulin \[1/IF\] from baseline to 9M., Baseline and 9 months|Change in OGTT derived biomarkers: c-peptide, Change in c-peptide from baseline to 6M calculated as \[change in C-peptide from 0-30min\] /\[change in glucose from 0-30 min\]. This computes for early c-peptide response to oral glucose., Baseline and 6 months|Change in OGTT derived biomarkers: c-peptide, Change in c-peptide from baseline to 9M calculated as \[change in C-peptide from 0-30min\] /\[change in glucose from 0-30 min\]. This computes for early c-peptide response to oral glucose., Baseline and 9 months|Change in OGTT derived biomarkers: fasting c-peptide, Change in fasting c-peptide from baseline to 6M calculated as Fasting C-peptide/Fasting Insulin., Baseline and 6 months|Change in OGTT derived biomarkers: fasting c-peptide, Change in fasting c-peptide from baseline to 9M calculated as Fasting C-peptide/Fasting Insulin., Baseline and 9 months|Time to glucose peak, Identification of time to glucose peak during OGTT at baseline., Baseline|Time to glucose peak, Identification of time to glucose peak during OGTT at 6M., 6 months|Time to glucose peak, Identification of time to glucose peak during OGTT at 9M., 9 months|Glucagon levels, Identification of glucagon levels during OGTT at baseline., Baseline|Glucagon levels, Identification of glucagon levels during OGTT at 6M., 6 months|Glucagon levels, Identification of glucagon levels during OGTT at 9M., 9 months|Incretin effect, Estimated as the ratio between total insulin responses during OGTT and IVGTT at the end of treatment and expressed as percentage. It is computed by: \[100% × (AUCins OGTT - AUCins IVGTT)/AUCins OGTT\]., 6 months|Incretin effect, Estimated as the ratio between total insulin responses during OGTT and IVGTT at the end of the wash-out period and expressed as percentage. It is computed by: \[100% × (AUCins OGTT - AUCins IVGTT)/AUCins OGTT\]., 9 months|Change in Protein Density Fat Fraction (PDFF), The change in PDFF from baseline to 9M after the wash-out period is calculated as the difference between 9M PDFF value and Baseline PDFF. It provides an accurate, non-invasive, reproducible, quantitative, and precise estimation of liver fat content. The expected changes in MRI-PDFF from baseline to 9M is ≥ 5.8% reduction compared to the placebo group., Baseline and 9 months|Fractional rates of de Novo Lipogenesis (DNL), It is the measure of contribution of hepatic DNL and plasma free fatty acid reesterification to plasma triglyceride secretion at baseline. It is calculated by F = plasma palmitate enrichment/(22 X plasma deuterium enrichment). F is the fraction of palmitate synthesized during the time between the loading dose of the deuterium-labeled water and the collection time., Baseline|Fractional rates of de Novo Lipogenesis (DNL), It is the measure of contribution of hepatic DNL and plasma free fatty acid reesterification to plasma triglyceride secretion at 6M. It is calculated by F = plasma palmitate enrichment/(22 X plasma deuterium enrichment). F is the fraction of palmitate synthesized during the time between the loading dose of the deuterium-labeled water and the collection time., 6 months|Fractional rates of de Novo Lipogenesis (DNL), It is the measure of contribution of hepatic DNL and plasma free fatty acid reesterification to plasma triglyceride secretion at 9M. It is calculated by F = plasma palmitate enrichment/(22 X plasma deuterium enrichment). F is the fraction of palmitate synthesized during the time between the loading dose of the deuterium-labeled water and the collection time., 9 months|Total cholesterol, Measure of total cholesterol in plasma taken at 6M., 6 months|Total cholesterol, Measure of total cholesterol in plasma taken at 9M., 9 months|LDL cholesterol, Measure of LDL cholesterol in plasma taken at 6M., 6 months|LDL cholesterol, Measure of LDL cholesterol in plasma taken at 9M., 9 months|HDL cholesterol, Measure of HDL cholesterol in plasma taken at 6M., 6 months|HDL cholesterol, Measure of LDL cholesterol in plasma taken at 9M., 9 months|Triglycerides, Measures of triglycerides in plasma taken at 6M., 6 months|Triglycerides, Measures of triglycerides in plasma taken at 9M., 9 months | Other: Changes in liver fibrosis, Changes in fibrosis of the liver as measured by the difference between MRE Stiffness during baseline and 6M., 6 months|Changes in liver fibrosis, Changes in fibrosis of the liver as measured by the difference between MRE Stiffness during baseline and 9M., 9 months
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