• Visit 2 during the run-in phase has been omitted, as the visit was primarily implemented for controlling of patients’ compliance which will be assessed anyway at randomization visit. • Inclusion criterion 1: new: ≤ 85 years old; old: < 85 years old. • Inclusion criterion 3: new: HbA1c ≥ 6.5%; old: HbA1c > 7.0%. • Exclusion criterion 8 has been specified allowing investigators to assess individually a necessary lapse of time preceding registration for patients with implantable cardioverter-defibrillator (ICD) and pacemaker. • Exclusion criterion 16: new: active tumor disease; old: malignancies within the past 5 years (except carcinoma in situ of the cervix and non melanomatous skin cancer). • Definition of MRI compatibility has been included to optimize scheduling the cardiac MRI procedure. • Plasma volume assessment will only be performed in a subgroup of patients due to organizational issues. Patients will be assigned to this examination consecutively beginning from a certain time point in order not to compromise randomisation balance. • In addition to DNA extraction, the biobanking samples will be used for RNA extraction also. • Introduction of time range for randomisation visit. This visit may be postponed for a week due to e.g. bank holidays, patient’s medical condition or other patient’s related issues. The time range for visit 3 and visit 4 was also extended, up to 7 days. • CTP section related to adverse events of special interest was completed.

Until April 2019, 54 patients have been randomized within the recruitment period of approximately 29 months since enrolment of the first patient (22 patients in EFFORT-1, 32 patients in EFFORT-2). It was decided to terminate inclusion of patients into the study by the end of 2019, last patient last visit date in January 2021. From a statistical point of view, EFFORT-1, originally planned as a confirmatory study, with a calculated necessary sample size of 200 patients, will now have, with an expected sample size of less than 50 patients, only very low power to detect a difference between treatment arms. So, EFFORT-1, in the same way as planned from the beginning for EFFORT-2, is now regarded as an exploratory hypotheses generating study.