A systematic review and meta-analysis of randomized controlled trials (RCTs) published in the Journal of Cardiac Failure assessed the clinical impact of initiating sodium–glucose cotransporter-2 inhibitors (SGLT2i) during hospitalization for acute heart failure (AHF). Major databases were searched through September 10, 2025 to identify eligible RCTs comparing in-hospital SGLT2i initiation versus control. 

Primary endpoints included all-cause mortality and worsening HF, while secondary outcomes comprised cardiovascular (CV) death, HF rehospitalization, and safety events. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models, and trial sequential analysis (TSA) evaluated the robustness of findings.

Eight RCTs involving 4,096 patients were included, with a weighted median follow-up of 60 days. In-hospital initiation of SGLT2i was associated with a reduction in all-cause mortality (RR 0.61; 95% CI 0.47–0.81) and worsening HF events (RR 0.67; 95% CI 0.48–0.94). A significant reduction in CV mortality was also observed (RR 0.68; 95% CI 0.47–0.99). No statistically significant difference was identified in HF rehospitalization rates (RR 0.87; 95% CI 0.70–1.09). 

Safety outcomes, including acute kidney injury, hypotension, hypoglycemia, urinary tract infection, and serious adverse events, were comparable between groups. TSA indicated sufficient evidence supporting mortality reduction, while further studies are required for worsening HF outcomes.

In-hospital SGLT2i initiation was associated with reduced mortality and worsening HF in AHF. Safety outcomes were comparable, though additional long-term data are needed to confirm sustained benefits.