Background: Heart failure (HF) is one of the leading public health problems with a substantial
burden in the global healthcare system. Although significant efforts are based on prevention,
early recognition, and proper management of HF, the worldwide surge of risk factors like hypertension,
diabetes, and obesity has further complicated the existing problem.
Objective: This study aims to define the role of the sodium-glucose cotransporter 2 (SGLT2) inhibitors
in non-diabetic HF.
Methods: We performed a comprehensive literature review to examine the available evidence in
the clinical implications of SGLT2 inhibitors in non-diabetic HF using the online databases
(PubMed and Embase).
Results: We identified two RCTs-DAPA-HF and DEFINE-HF, which were conducted to analyze
the net clinical benefit of dapagliflozin in non-diabetic HF patients. Although we could not study
the composite effects of these studies due to the difference in outcome measures, the individual outcomes
look promising. The number needed to treat (NNT) to prevent one primary event was 21
(95% CI: 15 to 38) in the DAPA study. In DEFINE HF study, responder analysis showed a significant
proportion of patients in the treatment arm experienced improvements in the functional status
with clinically meaningful improvement in KCCQ-OS by 3.7 points and KCCQ-CS by 4.6 points
with NNT of 10 and 7, respectively, at 12 weeks. Both studies also showed low safety concerns in
patients without T2D.
Conclusion: The outcomes of the two RCTs, DAPA-HF and DEFINE-HF, that studied the effects
of SGLT2 inhibitors in non-diabetic HF showed promising clinical outcomes. Although we are
waiting for other prospective RCTs to reflect similar results and safety profiles, it seems the
SGLT2 inhibitors can have broader clinical implications in managing non-diabetic HF with improved