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.
Condition: Diabetes Mellitus, Type 2; Kidney Function Tests
MeSH terms: Renal Insufficiency; Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Dapagliflozin
Intervention description: The study consists of a 2-week, open label, dapagliflozin (10mg) treatment period.
Intervention MeSH terms: Dapagliflozin
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 24.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

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 <10%
             (<86 mmol/mol); and eGFR (CKD-EPI) between ≥25 and ≤50 mL/min/1.73m2 or between >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