SGLT2i & GLP-1RAIncretin and Treatment With Inhibition of Sodium-glucose Cotransporter-2 Combination Insights Into Mechanisms Implicated in Congestive Heart Failure: "NATRIURETIC" Trial

Inclusion Criteria:

1. Men and women diagnosed with T2D ≥6 months prior to informed consent;
2. eGFR ≥30 mL/min/1.73m2;
3. Age >18 years;
4. HbA1c 7.0%-12.0%;
5. Body Mass Index (BMI) 18.5-40.0 kg/m2;
6. Stable HbA1c, measured 2-12 months prior to screening, within 5% of baseline value;
7. Blood pressure ≤160/100 mmHg at screening, >90/60 mmHg;
8. Stable on dose of ACE inhibitor, angiotensin receptor blocker or renin inhibitor for at least 2 weeks.

Exclusion Criteria:

1. Type 1 Diabetes;
2. Leukocyte and/or nitrite positive urinalysis that is untreated;
3. Severe hypoglycaemia within 2 months prior to screening;
4. History of hypoglycaemia unawareness based on investigator judgement;
5. Unstable coronary artery disease with acute coronary syndrome, percutaneous intervention or bypass surgery within 3 months;
6. Clinically significant valvular disease subject to PI/Sub PI's discretion;
7. Congestive heart failure subject to PI/Sub PI's discretion;
8. Bariatric surgery or other surgeries that induce chronic malabsorption within one year;
9. Anti-obesity drugs or diet regimen and unstable body weight three months prior to screening;
10. Treatment with systemic corticosteroids;
11. Blood dyscrasias or any disorders causing hemolysis or unstable red blood cells;
12. Pre-menopausal women who are nursing, pregnant, or of child-bearing potential and not practicing an acceptable method of birth control;
13. Participation in another trial with an investigational drug within 30 days of informed consent;
14. Alcohol or drug abuse within three months prior to informed consent that would interfere with trial participation or any ongoing clinical condition that would jeopardize subject safety or study compliance based on investigator judgement;
15. Liver disease, defined by serum levels of alanine transaminase, aspartate transaminase, or alkaline phosphatase >3 x upper limit of normal as determined during screening;
16. Medical history of cancer or treatment for cancer in the last five years prior to screening;
17. History of pancreatitis;
18. Personal of family history of medullary thyroid cancer or MEN2B;
19. Tachycardia, HR >100;
20. Use of SGLT2i, GLP-1RA or DPP-4i within the past 1 month (1-month minimum washout is allowed);
21. History of gastroparesis;
22. Known intolerance to SGLT2i or GLP-1RA;
23. Allergy to iodine-based substances if receiving iohexol for GFR measures.