“In-Hospital Initiation of SGLT-2 Inhibitors in Acute Heart Failure: A Systematic Review and Meta-Analysis of Clinical, Decongestion, and Safety Outcomes”

Background Acute heart failure (AHF) carries high morbidity and mortality and is traditionally managed with diuretics, vasodilators, and inotropes. Although guidelines recommend SGLT-2 inhibitors for chronic heart failure to reduce morbidity and mortality, their efficacy and safety when initiated during AHF hospitalization remain incompletely defined. To address this gap, we performed the largest, most contemporary meta-analysis focused exclusively on in-hospital initiation, including the first comprehensive pooled evaluation of decongestion outcomes. Methods We systematically searched PubMed, Scopus, Cochrane CENTRAL, and Google Scholar from inception to February 7, 2026, following PRISMA 2020 guidelines and a pre-registered PROSPERO protocol. Eligible studies were randomized controlled trials enrolling adults hospitalized with AHF receiving in-hospital SGLT-2 inhibitors versus placebo/standard care. Random-effects models (REML) pooled clinical, decongestion, and safety outcomes. Results Eighteen RCTs (n = 15,560) were included. In-hospital SGLT-2 initiation significantly reduced heart failure worsening or hospitalization (RR 0.77, 95% CI 0.67–0.88; NNT = 48) and improved quality of life (KCCQ-12 MD + 2.88 points, p = 0.01). Decongestion outcomes favored SGLT-2 inhibitors, with improved diuretic efficiency (SMD 0.52, p = 0.001), greater weight loss (MD − 0.94 kg, p < 0.001), and lower NT-proBNP (MD − 313.6 pg/mL, p = 0.04). All-cause mortality showed a modest reduction (RR 0.74, p = 0.035) but demonstrated potential publication bias and was attenuated in trim-and-fill analysis. Cardiovascular and non-cardiovascular death, and hospitalization length, were not significantly different. Critically, no increase was detected in AKI, hypotension, hypoglycemia, ketoacidosis, genitourinary infections, or other serious adverse events. Conclusions In-hospital SGLT-2 inhibitor initiation appears safe and is associated with reduced clinical events and modest improvements in decongestion markers. These findings support early in-hospital initiation as a feasible and safe strategy, although the current evidence, while promising, highlights the need for further long-term confirmatory data and provides a basis for potential updates to acute heart failure guidelines. PROSPERO ID: CRD420261297253. Graphical Abstract In-Hospital SGLT-2 Inhibitor Initiation in Acute Heart Failure. Legend: Pooled analysis of 18 RCTs (n=15,560) shows in-hospital SGLT-2 inhibitorinitiation significantly reduces heart failure worsening or hospitalization (RR 0.77; NNT=48),improves quality of life, and enhances decongestion (improved diuretic efficiency, weightloss, NT-proBNP reduction). All-cause mortality demonstrated a modest, less robustreduction. Safety outcomes were comparable to control, supporting early initiation in acuteheart failure.