the study will evaluate average 24-hr sodium excretion during dapagliflozin treatment in patients with type 2 diabetes mellitus with preserved or impaired renal function or non-diabetics with impaired renal function.

Conditions: Diabetes Mellitus, Type 2; Kidney Function Tests

Summary: the purpose of this study is to evaluate how dapagliflozin mechanism of action is impacted by type 2 diabetes mellitus status and kidney function


Eligibility criteria:
inclusion criteria: * provision of signed and dated, written informed consent prior to any study specific procedures * female and/or male aged between 18 years and ≤80 years * in the diabetic arms - a diagnosis of t2dm with hba1c ≥6.5% (≥48 mmol/mol) and \ 90 and ≤130 ml/min/1.73m2 for patients aged 59 years or younger, between \>85 and ≤130 ml/min/1.73m2 for patients aged 60 to 69 years, and between \>75 and ≤130 ml/min/1.73m2 for patients aged 70 years or older at the screening visit (visit 1) * in the non-diabetic arm, hba1c \<6.5% (\<48 mmol/mol) and an egfr (ckd-epi) between ≥25 and ≤50 ml/min/1.73m2 at the screening visit (visit 1) * patient specific optimal antihypertensive dose of an angiotensin receptor blocker at least 6 weeks before study treatment * in the diabetic arm (group 2) an appropriate stable dose of metformin, or sulphonylurea, or metformin+sulphonylurea as anti-diabetic therapy for the last 12 weeks before study treatment * stable urinary sodium excretion on 2 successive 24-hr urinary sodium excretion measurements. * in the diabetic arm with impaired renal function (group 1), a stable insulin dosing (intermediate, long-acting, premixed insulin, basal bolus insulin) for the last 12 weeks prior to visit 4 (day 1), as judged by the investigator. metformin or sulphonylurea, or metformin+sulphonylurea together with insulin would be accepted, but is not mandatory. if used, stable dose of metformin or sulphonylurea, or metformin+sulphonylurea as anti-diabetic therapy for the last 12 weeks prior to visit 4 (day 1) is required. exclusion criteria: * diagnosis of type 1 diabetes mellitus * any of the following cardiovascular/vascular diseases within 3 months prior to signing the consent; myocardial infarction, cardiac surgery or revascularization, unstable angina, unstable heart failure, heart failure nyha class iv, transient ischemic attack or significant cerebrovascular disease, unstable or previously undiagnosed arrhythmia * symptoms/complaints suggestive of established neurogenic bladder and/or incomplete bladder emptying * history of bladder cancer, diagnosis of polycystic kidney disease, history or current lupus nephritis or unstable or rapidly progressing renal disease * uacr \>1000 mg/g at screening * current/chronic use of the following medications: any anti-diabetic medication with the exception of metformin, sulphonylurea, angiotensin converting enzyme inhibitors, insulin (insulin only allowed in group 1), oral glucocorticoids, non-steroidal anti-inflammatory drugs, immune suppressants, chemotherapeutics, antipsychotics, tricyclic antidepressants and monoamine oxidase inhibitors * receiving immunosuppressive or other immunotherapy for primary or secondary renal disease within 6 months prior to screening * current treatment or treatment within the last 2 weeks prior to screening with diuretics including loop diuretics, thiazides, and mineralocorticoid antagonists