A Clinical Study to Investigate the Effects of Dapagliflozin on Heart Work, Heart Nutrient Uptake, and Heart Muscle Efficiency in Type 2 Diabetes Patients

Inclusion Criteria

• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
• Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses.
• Females or males ≥40 years up to 75 years of age.
• Individuals with type 2 diabetes diagnosed for at least 6 months based on the American Diabetes Association standards (ADA, 2017) and on stable dose of metformin for at least 6 weeks prior to screening and HbA1c at screening visit of ≥42 mmol/mol (6.0%) and ≤75 mmol/mol (9.0%) measured at local hospital laboratory.
• No significant signs or symptoms of coronary artery disease or, if known coronary artery disease, currently free of symptoms and a) all major epicardial vessels with 160 mmHg or diastolic blood pressure >100 mmHg.
• History of stroke or other clinically significant cerebrovascular disease.
• Any of the following cardiovascular diseases known within 3 months prior to signing the consent at enrolment:
• Atrial fibrillation, or other unstable or severe arrhythmia affecting heart function
• Unstable heart failure or any heart failure with NYHA class III and IV
• Significant valvular disease
• Significant peripheral artery disease
• Planned cardiac surgery or angioplasty within 3 months from enrolment.
• Clinical diagnosis of type 1 diabetes, maturity onset diabetes of the young (MODY), secondary diabetes or diabetes insipidus.
• Verified body weight variability of >3 kg during the 3 proceeding months before screening.
• Active malignancy requiring treatment at the time of visit 1 (with the exception of successfully treated basal cell or treated squamous cell carcinoma).
• Patients with severe hepatic impairment (Child-Pugh class C).
• Unstable or rapidly progressing renal disease.
• Clinically significant disease or disorder which, in the opinion of the investigator, may either put the subject at risk because of participation in the study, or influence the results or the subject's ability to participate in the study.
• Ongoing treatment with other antidiabetic drugs than metformin.
• Ongoing treatment with loop diuretics.
• Ongoing weight-loss diet (hypocaloric diet) or use of weight loss agents.
• Contraindications to dapagliflozin therapy.
• Ongoing treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except for T2D.
• Previous enrolment in the present study or participation in another clinical study with an investigational product during the last 1 month prior to screening.
• Estimated Glomerular Filtration Rate (eGFR) 450 mL during the 3 months prior to screening.
• Women who has a positive pregnancy test at enrolment or randomization, or are breastfeeding.