DiEtary Sodium Intake Effects on Ertugliflozin-induced Changes in GFR, reNal Oxygenation and Systemic Hemodynamics: the DESIGN Study (DESIGN)

Inclusion Criteria: Adults with previously diagnosed T2DM according to American Diabetes Association (ADA) criteria HbA1c 6.5-10% Age 35-80 years of age Overweight or obese with BMI: >25 kg/m2 We will make every effort to enrol participants of all races/ethnicities." Both sexes (females must be post-menopausal; no menses >1 year; in case of doubt, Follicle-Stimulating Hormone (FSH) will be determined with cut-off defined as >31 U/L) Ability to provide signed and dated, written informed consent prior to any study procedures Estimated GFR 60-90 ml/min/1.73m2 by CKD-EPI matching the eGFR range of most participants in VERTIS-CV Sodium intake at baseline < 200 mmol/day UACR < 30 mg/mmol All participants need to be on a stable dose of Diabetes medication, including Metformin, SU, insulin All participants need to be on a stable dose of RAS inhibition Exclusion Criteria: History of unstable or rapidly progressing renal disease Estimated GFR <60 mL/min/1.73m2 or eGFR > 90 mL/min/1.73m2 determined by CKD-EPI UACR > 30 mg/mmol Current/chronic use of the following medication: SGLT2 inhibitors, TZD, GLP-1RA, glucocorticoids, immune suppressants, antimicrobial agents, chemotherapeutics, antipsychotics, tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). Subjects on diuretics will only be excluded when these drugs cannot be stopped for the duration of the study. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDs) will not be allowed, unless used as incidental medication (1-2 tablets) for non-chronic indications (i.e. sports injury, headache or back ache). However, no such drug can be taken within a timeframe of 2 weeks prior to renal testing History of diabetic ketoacidosis (DKA) requiring medical intervention (e.g. emergency room visit and/or hospitalization) within 1 month prior to the Screening visit. Current urinary tract infection and active nephritis Recent (<6 months) history of cardiovascular disease, including: Acute coronary syndrome Chronic heart failure (New York Heart Association grade II-IV) Stroke or transient ischemic neurologic disorder Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal (ULN) and/or alanine aminotransferase (ALT) >3x ULN History of or actual malignancy (except basal cell carcinoma) History of or actual severe mental disease Substance abuse (alcohol: defined as >4 units/day) Allergy to any of the agents used in the study Individuals who are investigator site personnel, directly affiliated with the study, or are immediate (spouse, parent, child, or sibling, whether biological or legally adopted) family of investigator site personnel directly affiliated with the study Inability to understand the study protocol or give informed consent