THE ROLE OF SGLT2 INHIBITORS BEYOND DIABETES IN HEART FAILURE: EVIDENCE FROM RECENT TRIALS

Abstract

Background: Heart failure remains a leading global cause of morbidity and mortality, with limited therapeutic options, especially for patients with preserved ejection fraction (HFpEF). Sodium-glucose cotransporter-2 (SGLT2) inhibitors, initially developed for glycemic control in type 2 diabetes mellitus (T2DM), have shown cardioprotective effects beyond glucose lowering. Objective: This systematic review aimed to critically appraise evidence from recent randomized controlled trials evaluating the efficacy and safety of SGLT2 inhibitors in heart failure patients, regardless of diabetes status. Methods: A narrative synthesis was conducted using data from four pivotal RCTs: DAPA-HF, EMPEROR-Reduced, EMPEROR-Preserved, and DELIVER, collectively enrolling over 21,000 patients with varying ejection fractions. Results: Across trials, SGLT2 inhibitors (dapagliflozin and empagliflozin) consistently reduced the composite risk of cardiovascular death or heart failure hospitalization by approximately 18–30%. Benefits appeared early, were sustained throughout follow-up, and were similar in diabetic and non-diabetic patients. Adverse events were infrequent; hypoglycemia was negligible in non-diabetic patients, with a small increase in genital infections. Conclusion: These findings have led to updated clinical guidelines recommending SGLT2 inhibitors as cornerstone therapy for HFrEF and as first-line pharmacologic options for HFpEF. Continued research is warranted to explore long-term outcomes and optimal therapeutic combinations.

Keywords:  Heart Failure; SGLT2 Inhibitors; Dapagliflozin; Empagliflozin; HFrEF; HFpEF; Cardiovascular Outcomes; Diabetes; Randomized Controlled Trials