Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are cornerstone therapy in heart failure (HF), but their relative effectiveness across the ejection fraction (EF) spectrum is uncertain. This was a systematic review after the PRISMA 2020 guidelines were applied to guide the assessment. From database inception to 2025, in-depth searches was conducted through PubMed/MEDLINE and Web of Science, Cochrane CENTRAL, and Google Scholar. Randomized controlled trials (RCTs) and comparative observational studies assessing the efficacy and safety of SGLT2 inhibitors in HF with reduced or preserved EF were included. Risk of bias was assessed using the Cochrane RoB 2.0 tool for RCTs and ROBINS-I for non-randomized studies. Of 1,306 identified records, 15 studies met the inclusion criteria, encompassing over 1.5 million participants. Across trials and real-world cohorts, SGLT2 inhibitors significantly reduced heart failure hospitalizations by 20–30% and cardiovascular death by up to 25%, with benefits observed regardless of diabetes status or EF category. Empagliflozin and dapagliflozin consistently improved composite cardiovascular outcomes, renal function, and quality of life, while adverse events were mild and infrequent. Empagliflozin showed slightly greater effects on ventricular remodeling than dapagliflozin. Most RCTs demonstrated moderate quality with unclear blinding risk; non-randomized studies showed variable but generally low to moderate bias. SGLT2 inhibitors provided consistent cardio-renal benefits and reduced hospitalization and mortality risks across the HF spectrum. Their favorable safety profile supports early integration into guideline-directed therapy for both HFrEF and HFpEF patients.

Key words: SGLT2 inhibitors, heart failure, ejection fraction, cardiovascular outcomes, PRISMA.