The investigators propose a small pilot proof of concept study to not only prove the existence of, but also probe the mechanisms underlying cardio-renal effects of empagliflozin in patients with heart failure. The investigators propose a 50 patient randomized, double-blind, placebo-controlled crossover study with patients with stable HF, type II diabetes and an eGFR >45ml/min/1.73 m2 who are chronically receiving loop diuretics.

Study Objectives

1. Study the acute/short term effect and cardio-renal mechanisms of sodium-glucose cotransporter 2 (SGLT2) inhibition in patients with heart failure.
2. Determine the effect of chronic combined SLLGT2 and loop diuretic exposure in patients with heart failure.

Primary Outcomes

1. Aim 1 (Acute): Determine if acute SGLT2 inhibition will improve the natriuretic effect of a loop diuretic compared to placebo.
2. Aim 2 (Chronic): Determine the effect of 14 days of SGLT2 inhibition on blood volume.

Inclusion Criteria:

• Stable HF as defined by:
• No hospitalization for >60 days
• Stable HF medications for >=2 weeks, and stable diuretics for 4 weeks
• Opinion of HF cardiologist that the patient is at their optimal volume status
• Chronic daily oral loop diuretic dose >=20mg furosemide equivalents
• Diagnosis of type II diabetes
• Patient monitors blood glucose regularly at home
• eGFR >=45 mL/min/1.73 m2
• >=18 years old

Exclusion Criteria:

• Active titration of chronic HF medications expected during the study period
• Use of a non-loop diuretic, aside from an aldosterone antagonist (<=25mg spironolactone or <=50mg eplerenone)
• Critical stenotic valvular disease, complex congenital heart disease, or prior heart transplant
• History of diabetic ketoacidosis, "brittle" diabetes, and/or frequent hypoglycemia or severe hypoglycemic episodes requiring emergent intervention (ER visit or EMS response, glucagon administration or forced oral carbs) in the last 6 months
• History of bladder dysfunction, incontinence, pyelonephritis, urosepsis, or frequent urinary tract infections
• Anemia (defined as hemoglobin <8g/dL)
• Pregnancy or breastfeeding
• History of serious hypersensitivity
• Participation in another trial with an investigational drug within the 30 days prior to informed consent
• Use of another SGLT-2 inhibitor
• Appears unlikely, or unable to participate in the required study procedures, as assessed by the study PI or research RN (ex: clinically-significant psychiatric, addictive, or neurological disease)
• Inability to give written informed consent or follow study protocol