Functional Impact of GLP-1 for Heart Failure Treatment (FIGHT)

Inclusion Criteria:

Age ≥ 18 years
AHFS as defined by the presence of at least 1 symptom (dyspnea, orthopnea, or edema) AND 1 sign (rales on auscultation, peripheral edema, ascites, pulmonary vascular congestion on chest radiography)
AHFS is the primary cause of hospitalization
Prior clinical diagnosis of HF
Left Ventricular Ejection Fraction(LVEF) ≤ 40% during the preceding 3 months (if no echo within the preceding 3 months, an LVEF ≤ 30% during the preceding three years is acceptable)
On evidence-based medication for HF (including beta-blocker and ACE-inhibitor/ARB) or previously deemed intolerant
Use of at least 80 mg or furosemide total daily dose (or equivalent) prior to admission for AHFS (a lower dose of a loop diuretic combined with a thiazide will count as an "equivalent")
Willingness to provide informed consent

Exclusion Criteria:

AHFS due to acute myocarditis or acute Myocardial Infarction
Ongoing hemodynamically significant arrhythmias contributing to HF decompensation
Inotrope, intra-aortic balloon pump (IABP) or other mechanical circulatory support use at the time of consent. Prior use will not exclude a patient.
Current or planned left ventricular assist device therapy in next 180 days
United Network for Organ Sharing status 1A or 1B
B-type natriuretic peptide(BNP)< 250 or NT-proBNP<1,000 (Not required per protocol but if available and too low would be an exclusion; within 48 hours of consent)
Hemoglobin (Hgb) < 8.0 g/dl
Glomerular filtration rate(GFR) < 20 ml/min/1.73 m2 within 48 hours of consent
Systolic blood pressure < 80 mmHg at consent
Resting Heart Rate > 110 at consent
Acute coronary syndrome within 4 weeks as defined by electrocardiographic (ECG) changes and biomarkers of myocardial necrosis (e.g. troponin) in an appropriate clinical setting (chest discomfort or anginal equivalent)
Percutaneous Coronary Intervention, coronary artery bypass grafting or new biventricular pacing within past 4 weeks
Primary hypertrophic cardiomyopathy
Infiltrative cardiomyopathy
Constrictive pericarditis or tamponade
Complex congenital heart disease
Non-cardiac pulmonary edema
More than moderate aortic or mitral stenosis
Intrinsic (prolapse, rheumatic) valve disease with severe mitral, aortic or tricuspid regurgitation
Sepsis, active infection (excluding cystitis) or other comorbidity driving the HF decompensation
Acute or chronic severe liver disease as evidenced by any of the following: encephalopathy, variceal bleeding, International Normalized Ration (INR) > 1.7 in the absence of anticoagulation treatment
Terminal illness (other than HF) with expected survival of less than 1 year
Previous adverse reaction to the study drug
Receipt of any investigational product in the previous 30 days.
Enrollment or planned enrollment in another randomized therapeutic clinical trial in next 6 months.
Inability to comply with planned study procedures
Pregnancy or breastfeeding mothers
Women of reproductive age not on adequate contraception
History of acute or chronic pancreatitis
History of symptomatic gastroparesis
Familial or personal history of medullary thyroid cancer or multiple endocrine neoplasia type-2 (MEN2)
Prior weight-loss surgery (i.e., Roux-en-Y gastric bypass) or other gastric surgery associated with increased endogenous GLP-1 production
Prior or ongoing treatment with GLP-1 receptor agonists
Ongoing treatment with dipeptidyl peptide-IV inhibitors (1 week washout required)
Ongoing treatment with thiazolidinedione
Oxygen-dependent chronic obstructive pulmonary disease
Diabetic patients with history of 2 or more severe hypoglycemia, Diabetic Ketoacidosis(DKA) or hyperglycemic, hyperosmotic nonketotic coma in the preceding 12 months.
Diagnosis of Type 1 Diabetes Mellitus

40. If diabetic, inadequate glycemic control with glucose level > 300 mg/dL within 24 hours of randomization