Date of Award


Document Type

Scholarly Project

Degree Name

Master of Physician Assistant Studies (MPAS)


Physician Assistant Studies

First Advisor

Russ Kauffman


Heart failure; Neuro-hormonal cell changes; Pathophysiologic cell changes; Sodium-glucose cotransporter 2; Cardiac electrolyte imbalance; Diabetic patients; Research


Heart failure remains a complex disease that affects a continually increasing number of patients annually. For heart failure, most of the research has focused on the hemodynamic changes of the heart chambers and the medication interventions that slow the progression of heart failure. Recent studies have investigated treatment options that may disrupt the neuro-hormonal and pathophysiologic cell changes that lead to further progression of heart failure. Although the mechanisms by which the sodium-glucose cotransporter 2 (SGLT2) inhibitors are not entirely understood, they are believed to directly affect the cardiac electrolyte imbalances that trigger the cellular changes which contribute to the altered contractility, adrenergic receptor changes, and resulting hemodynamic changes seen with heart failure. To evaluate SGLT2 inhibitors in the treatment of heart failure in diabetic and non-diabetic patients, placebo studies for SGLT2 inhibitors and current guideline-directed therapies including beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), mineralocorticoid receptor agonists (MRA), and angiotensin receptor-neprilysin inhibitors (ARNIs) were compared for each class of medications using the hazard ratios and confidences intervals of the all-cause mortality rates. The results showed that treatment with SGLT2 inhibitors in patients with heart failure with reduced ejection fraction (HFrEF) may be comparable to other guideline-directed therapies. Because of the lack of data specific to patients with heart failure with preserved ejection fraction (HFpEF), further research is needed to assess these medications’ efficacy in this population. When assessing the available pooled data for HFrEF and HFpEF patients, SGLT2 inhibitors appear to be a promising area of research compared to the recommended therapies for those with HFpEF.