| Outcome Measures: |
Primary: Change in glucose tolerance, Changes in glucose is measured by area under the curve for the plasma glucose excursion following a 4-hour 75 g oral glucose tolerance test (OGTT), from baseline to 52 wks, 53 wks, 260 wks, and 261 wks | Secondary: Deterioration in glycaemic status, Percentage of subjects in each treatment arm with normal glucose tolerance (NGT) at inclusion who develop impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) or type 2 diabetes; or with IFG or IGT who develop combined IFG/IGT; or with combined IFG/IGT who develop type 2 diabetes, from baseline to 52 wks, 53, wks, 260 wks, and 261 wks | Other: Changes in glycated hemoglobin, Changes in glycated hemoglobin (HbA1c). From normoglycaemic to prediabetic or type 2 diabetic and from prediabetic to type 2 diabetic or normoglycaemic., From baseline to 52 wks and 260 wks|Changes in anthropometric measurements, Changes in body mass index (BMI)(kg/m2), absolute body weight (kg), and waist:hip ratio, from baseline to 52 and 260 wks|Changes in beta cell secretory responses, changes in area under the curve during OGTT and isoglycemic intravenous glucose infusion (IIGI), the homeostatic model assessment (HOMA) and pro-insulin ratio, from baseline to 52, 53, 260, and 261 wks|Changes in insulin sensitivity, assessed by HOMA-IR and Matsuda insulin sensitivity index, from baseline to 52, 53, 260, and 261 wks|Changes in incretin hormone secretion, measured as fasting plasma concentrations and plasma responses of GLP-1, GLP2, and GIP and plasma glucagon during OGTT, baseline to 52, 53, 260, and 261 wks|Changes in incretin effect, insulin and c-peptide responses after OGTT vs. IIGI, baseline to 52, 53, 260, and 261 wks|Changes in presence of non-alcoholic fatty liver disease (NAFLD), gamma-glutamyltranferase (GGT), intra-heptic fat, FGF-21, whole body and visceral fat mass/fat-free mass, circulating lipids, ultrasound scan and fibroscan, baseline to 52 and 260 wks|Changes in cardio-metabolic risk measures, pro-collagen 3, GGT, Intra-hepatic fat, whole body and visceral fat mass/fat-free mass, circulating lipids and cardiovascular biomarkers (highly sensitive c-reactive protein (hs-CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), tumor necrosis factor-alpha (TNF-alpha), adiponectin and plasminogen activator inhibior-1 (PAI-1)), baseline to 52 and 260 wks|Changes in gut microbiota, optional to the main protocol, baseline to 52 and 260 wks|Changes in subjective appetite, visual analogue scale (VAS), baseline to 52, 53, 260, and 261 wks|Number of participants with treatment-related adverse events (Safety and tolerability), as assessed by validated questionnaires, baseline to 52 and 260 wks|Change in Quality of life, Assessed by validated questionnaires (SF-36), Baseline to 52 and 260 wks|Evaluation of alcohol consumption, By validated questionnaires, baseline to 52 and 260 wks|Evaluation of microalbuminuria, Predicitve value of biomarkers for detection of microalbuminuria, baseline to 52 to 260 wks|Evaluation of blindedness of participants and investigators, questionnaire and the end of the blinded trial, baseline to 52 wks|Changes in bonemarkers, baseline to 52 and 260 wks
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