Renal safety and clinical effectiveness of peri-hospitalization SGLT2 inhibitor initiation in acute heart failure: a systematic review and meta-analysis
J Gu, D Yow, S Chang, W Tan, S TanAbstract
Objectives
To evaluate the renal safety and clinical efficacy of initiating sodium–glucose cotransporter-2 (SGLT2) inhibitors during hospitalization for acute heart failure (AHF), with a focus on initiation timing.
Background
Concern for acute kidney injury (AKI) often delays in-hospital initiation of SGLT2 inhibitors. Whether early initiation (≤24 hours) or initiation during active decongestion exacerbates renal dysfunction remains unclear.
Methods
A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing in-hospital SGLT2 inhibitor initiation vs. placebo/usual care in AHF was conducted (PubMed/Embase through December 2025). The primary endpoint was a composite of AKI or worsening renal function (WRF). Secondary endpoints included cardiovascular death or worsening heart failure events. Subgroup analyses stratified initiation timing into early (≤24 hours) vs. stabilized phases.
Results
Six RCTs comprising 3,398 patients were included. Initiation ranged from ultra-early (<12 hours) to stabilized peri-discharge windows. In-hospital SGLT2 inhibitor initiation was not associated with an increased risk of AKI/WRF (111/1,711 [6.5%] vs. 107/1,687 [6.3%]; Risk Ratio: 0.97; 95% CI: 0.61–1.53; I² = 47%). This safety signal remained consistent across timing strata, including ultra-early initiation. For clinical efficacy, early initiation was associated with a reduction in cardiovascular death or worsening heart failure events (Hazard Ratio: 0.80; 95% CI: 0.65–0.99; I²=0%).
Conclusions
In patients hospitalized with AHF, peri-hospitalization initiation of SGLT2 inhibitors is safe regarding renal function and reduces post-discharge clinical events. These findings support initiation upon presentation rather than deferral until outpatient follow-up.