Appendix A: Full Inclusion/Exclusion Criteria Inclusion Criteria: For inclusion in the study patients should fulfill the following criteria: 1. Provision of informed consent prior to any study specific procedures (including run-in) 2. Female or male aged 40 trial ≥ 3. Diagnosed with T2DM 4. High Risk for CV event defined as having either established CV disease and/or multiple risk factors: Established CV Disease (See Appendix E for details) − OR No known cardiovascular disease AND at least two cardiovascular risk factors in addition to T2DM, defined as: Age > 55 in men and > 60 in women − AND presence of at least 1 of the following additional risk factors (see Appendix E for details) Dyslipidemia − Hypertension − Tobacco use − - 5. WOCBP must take precautions to avoid pregnancy throughout the study and for 4 weeks after intake of the last dose. WOCBP must have a negative urine pregnancy test. WOCBP include any female who has − experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral ligation or bilateral oophorectomy) or is not postmenopausal. must be willing to use a medically accepted method of contraception that is − considered reliable in the judgment of the Investigator. For inclusion in the optional genetic research, patients must fulfill the criterion specified in Exclusion Criteria: Patients should not meet any exclusion criteria at the time of randomization. If at the time of enrollment, it is known that the patient will not meet criteria after a successful run-in period he/she should not be entered into run in. 1. Use of the following excluded medications: Current or recent (within 24 months) treatment with pioglitazone and/or use of • pioglitazone for 2 or more at any time Current or recent (within 12 months) treatment with rosiglitazone • Previous treatment with any SGLT2 inhibitor • Any patient currently receiving chronic (>30 consecutive days) treatment with an • oral steroid at a dose equivalent to oral prednisolone mg (e.g., betamethasone ≥10 mg, dexamethasone mg, hydrocortisone mg) per day ≥1.2 ≥1.5 ≥40 2. Acute cardiovascular event [e.g., acute coronary syndrome (ACS), transient ischemic
Appendix A: Full Inclusion/Exclusion Criteria Inclusion Criteria: For inclusion in the study patients should fulfill the following criteria: 1. Provision of informed consent prior to any study specific procedures (including run-in) 2. Female or male aged ≥ 40 3. Diagnosed with T2DM 4. High Risk for CV event defined as having either established CV disease and/or multiple risk factors: − Established CV Disease (See Appendix E for details) OR No known cardiovascular disease AND at least two cardiovascular risk factors in addition to T2DM, defined as: − Age > 55 in men and > 60 in women AND presence of at least 1 of the following additional risk factors (see Appendix E for details) − Dyslipidemia − Hypertension − Tobacco use - 5. WOCBP must take precautions to avoid pregnancy throughout the study and for 4 weeks after intake of the last dose. − WOCBP must have a negative urine pregnancy test. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral ligation or bilateral oophorectomy) or is not postmenopausal. − must be willing to use a medically accepted method of contraception that is considered reliable in the judgment of the Investigator. For inclusion in the optional genetic research, patients must fulfill the criterion specified in Exclusion Criteria: Patients should not meet any exclusion criteria at the time of randomization. If at the time of enrollment, it is known that the patient will not meet criteria after a successful run-in period he/she should not be entered into run in. 1. Use of the following excluded medications: • Current or recent (within 24 months) treatment with pioglitazone and/or use of pioglitazone for 2 or more at any time • Current or recent (within 12 months) treatment with rosiglitazone • Previous treatment with any SGLT2 inhibitor • Any patient currently receiving chronic (>30 consecutive days) treatment with an oral steroid at a dose equivalent to oral prednisolone ≥10 mg (e.g., betamethasone ≥1.2 mg, dexamethasone ≥1.5 mg, hydrocortisone ≥40 mg) per day 2. Acute cardiovascular event [e.g., acute coronary syndrome (ACS), transient ischemic trial