| Outcome Measures: |
Main Objective: To investigate the effect of the glucagon-like peptide-1 receptor agonist liraglutide on patophysiological characteristics and the risk of type 2 diabetes mellitus in women with previous gestational diabetes mellitus (GDM).;<br> Secondary Objective: To investigate if liraglutide has an effect on appetite which is different during OGTT and IIGI, if liraglutide improves the subjects' quality of life and bone mineral density.<br> To investigate if the quality of life in women with prior GDM and non-alcoholic fatty liver (NAFLD) is better or worse than women with prior GDM without NAFLD, women without prior GDM and without NAFLD and women with NAFLD who attend an outpatient clinic due to their liver disease.<br> ;Timepoint(s) of evaluation of this end point: After 52, 53, 260, and 261 weeks;Primary end point(s): Primary endpoint is the change in glucose tolerance from baseline to week 52 as measured by area under the curve (AUC) for the PG excursion following a 4-hour 75 g-oral glucose tolerance test (OGTT). Additional endpoints regarding glucose tolerance includes changes from baseline to week 53 (after trial medication wash-out) and at end of the study (260 weeks and 261 weeks (liraglutide-treated).<br> Secondary end point(s): 1) Percentage of subjects in each treatment arm with normal glucose tolerance (NGT: FPG = 6.0 mM and 2h PG < 7.8 mM) at inclusion who develop prediabetes (impaired fasting glucose (IFG): (6.1 mM = fasting PG (FPG) < 7.0 mM and 2h PG after 75 g-OGTT < 7.8 mM) and/or impaired glucose tolerance (IGT): (FPG < 6.1 mM and 7.8 mM = 2h PG after 75 g-OGTT = 11.0 mM) or T2DM (FPG= 7mM or 2h PG = 11.1 mM)<br> 2) Improvement in glycaemic status, as percentage of patients in each treatment arm going from:<br> ?€? IFG to normal glucose tolerance (FPG = 6.0 mM and 2h PG < 7.8 mM)<br> ?€? IGT to NGT<br> ?€? Combined IFG and IGT to IFG, IGT, or NGT<br> 3) Progression of isolated IFG or isolated IGT (at inclusion) to combined IFG/IGT or type 2 diabetes mellitus (T2DM), and progression of combined IFG/IGT (at inclusion) to T2DM<br> 4) Changes in glycosylated haemoglobin (HbA1c) as percentage of patients who progress from:<br> ?€? Normoglycaemic to prediabetic (HbA1c <6.0 ? 6.0-6.4)<br> ?€? Normoglycaemic to T2DM (HbA1c <6.0 ? = 6.5)<br> ?€? Prediabetic to T2DM (HbA1c 6.0-6.4 ? = 6.5)<br> or improves from:<br> ?€? Prediabetic to normoglycaemic (HbA1c 6.0-6.4 ? <6.0)<br> 5) Changes in anthropometric measurements (BMI, absolute body weight (kg) and waist:hip ratio)<br> 6) Changes in beta cell secretory responses (AUC for insulin and C-peptide) during OGTT and IIGI, the homeostatic model assessment (HOMA) and pro-insulin to insulin ratio)<br> 7) Changes in insulin sensitivity (assessment of insulin resistance (HOMAIR ) and Matsuda insulin sensitivity index)<br> 8) Changes in incretin hormone secretion (fasting plasma concentrations and plasma responses of GLP-1, GLP-2 and GIP) and plasma glucagon during OGTT<br> 9) Changes in incretin effect (insulin and C-peptide responses after OGTT vs. IIGI)<br> 10) Changes in gamma-glutamyltransferase (GGT), intra-hepatic fat, FGF-21, whole body and visceral fat mass/fat-free mass, circulating lipids and cardiovascular biomarkers (e.g.highly sensitive C-reactive protein (hs-CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), tumor necrosis factor-alpha (TNF-a), adiponectin and plasminogen activator inhibitor-1 (PAI-1) and RNA-oxidation)<br> 11) Changes in gut microbiota (optional to the main protocol)<br> 12) Changes in subjective appetite (measured by visual analogue scale (VAS))<br> 13) Safety and tolerability<br> 14) Evaluation of QoL will be judged by validated questionnaires<br> 15) Evaluation of alcohol consumption will be judged by validated questionnaires<br> 16) Evaluation of the predictive value of biomarkers for detection of microalbuminuria<br> 17) Evaluation of blindedness of participant and investigators by questionnaire and the end of the blinded part of the trial<br> 18) Changes in bone markers<br> ;Timepoint(s) of evaluation of this end point: All secondary endpoints will be assessed as changes from baseline until 52 weeks, and until end of the study (260 weeks). In addition, some endpoints (including 1, 2, 3, 6, 7, 8, 9, 10, 12 and 18 - above) will also be assessed as changes from baseline until week 53 and week 261 (after trial medication wash-out).
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