Sodium-Glucose Cotransporter Inhibitors in Non- Diabetic Heart Failure: A Narrative Review

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 cardiovascular outcomes.