| Outcome Measures: |
Primary: Change in peak early diastolic strain rate measured by cardiac MRI, It is now well recognised that diastolic dysfunction is the primary characteristic of heart disease in T2DM. Measured by gold-standard tagged cardiac MRI. MRI scans will be anonymised and sent to a stand-alone work station for independent analysis., Change from baseline peak end diastolic strain rate at 26 weeks | Secondary: Composite of standard biochemical variables, (measured blinded to treatment allocation by UHL Pathology labs measured at baseline, 12 weeks to 26 weeks) * HbA1c * Liver Function Tests * Renal Function Tests * Lipid profile including total-, LDL- and HDL-cholesterol and triglycerides * Thyroid function tests * Complete Blood Count (Hematocrit) * Vitamin D, Changes from baseline to 26 weeks|Composite chronic low-grade inflammation and adiposity, (measured blinded to treatment allocation in specialist laboratories at baseline, 12 weeks and 26 weeks): * Interleukin-6 * C-reactive protein * Leptin * Adiponectin, Changes from baseline to 26 weeks|Composite Endothelial Function, Assessed using biological markers. A blood sample will be taken at baseline and 26 weeks and the serum analysed using MSD multiplex panels for the following markers of vascular injury: * Panel 1) sICAM-3, e-Selectin, Thrombomodulin, * Panel 2) CRP, sICAM, sVCAM, SAA Evaluation of endothelial progenitor cells, stromal derived factor (SDF-1 and GLP-1) and associated biomarkers in a sub-set of participants., Changes from Baseline to 26 weeks|Composite Standard Anthropometric variables, Measures taken at baseline, 12 and 26 weeks * BMI * Weight * Percentage body fat * Waist and hip circumferences * Systolic and Diastolic Blood pressure (average of 3 measures taken 5 minutes apart) * Heart rate (after resting seated for at least 5 minutes, Changes from baseline to 26 weeks|MRI defined adiposity, • Subcutaneous, visceral and hepatic adiposity volumes (measured through semi-automated analysis), Changes from baseline to 26 weeks|Composite Lifestyle variables, Measured at baseline, 12 and 26 weeks * Cardio-respiratory fitness (graded VO2 max test) * Total physical activity and time in sedentary behaviour, light-, moderate-, and vigorous-intensity physical activity (ActiGraph GT3X accelerometer worn around the waist during waking hours for 7 consecutive days) * Sitting time (thigh mounted ActivPal inclinometer worn for 7 consecutive days), Changes from baseline to 26 weeks|Composite Quality of Life and Depression, Measured at baseline, 12 and 26 weeks * EQ5D * Hospital anxiety and depression score, Changes from baseline to 26 weeks|Composite treatment and satisfaction, Measured at baseline, 12 and 26 weeks • DTSQ, Changes from Baseline to 26 weeks|Composite Medication Usage, • Changes to SU, lipid lowering and anti-hypertensive medication usage recorded at baseline, 12 and 26 weeks, Changes from Baseline to 26 weeks|Composite Hypoglycemic Episodes, Self-reported in a standardized hypoglycemia diary., Changes from baseline to 26 weeks|Composite Outcomes, 1. HbA1c \<7.0%, no weight gain and no minor or major hypoglycemia 2. HbA1c \<7.0% and no weight gain 3. HbA1c \<7%, SBP \<130 mmHg, and no weight gain 4. HbA1c \<7% and SBP \<130 mmHg 5. Adverse events (see Section 16 for criteria), Post-26 week analysis|Composite MRI Outcomes, Other cardiac measures of function and structure will include: * Peak Systolic Strain * Left Ventricular Ejection Fraction * Stroke volume * LV end-diastolic volume * LV end-systolic volume * LV end-diastolic mass * Left Ventricular End Diastolic Mass/volume ratio * Pre-and post contrast T1 mapping to calculate volume of distribution, a marker of diffuse cardiac fibrosis * Myocardial Perfusion Reserve ( a measure of microvascular function), Change from baseline cardiac measures at 26 weeks|Composite 7 point glucose profile, Participants will be requested to provide a 7-point glucose profile measured at treatment initiation,12 and 26 week follow-up., Chanegs from baseline to 26 weeks
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