Key result
SGLT2 inhibitors cut CV death or worsening HF ~23% across the ejection fraction spectrum.
Why the study?
Although SGLT2 inhibitors form a pillar of HF therapy, whether their benefit is consistent across the full LVEF spectrum remained a key clinical question.
Do SGLT2 inhibitors reduce the composite of cardiovascular death or worsening heart failure in adults with heart failure across the left ventricular ejection fraction spectrum?
Meta-Analysis (n=22,477)
Double-blind with matching placebo in included trials
Centralised randomization in included trials
Yes
Do SGLT2 inhibitors reduce the composite of cardiovascular death or worsening heart failure in adults with heart failure across the left ventricular ejection fraction spectrum?
This meta-analysis demonstrates with high-certainty evidence that SGLT2 inhibitors consistently reduce cardiovascular death or worsening heart failure by 23% across the entire LVEF spectrum without heterogeneity, supporting their role as foundational therapy for all symptomatic heart failure patients regardless of ejection fraction.
Answers are grounded in this paper and cite their sources.
Supports SGLT2 inhibitors as foundational therapy across symptomatic heart failure; confirms and extends prior meta-analyses to the full LVEF spectrum.
Background: Sodium–glucose cotransporter-2 (SGLT2) inhibitors were developed as glucose-lowering drugs but now form a pillar of heart failure (HF) therapy. Whether their benefit is consistent across the full left ventricular ejection fraction (LVEF) spectrum remains a key clinical question. Methods: Following PRISMA 2020, we searched PubMed/MEDLINE, Embase, Cochrane CENTRAL and ClinicalTrials.gov for randomised placebo-controlled trials of SGLT2 inhibitors in adults with HF reporting clinical outcomes. Risk of bias was assessed with RoB 2 and certainty with GRADE. Trial-level hazard ratios (HRs) were pooled with a random-effects model, stratified by LVEF (≤ 40% vs > 40%). Results: Six trials (n = 22,477) were included; five event-driven trials (n = 21,947) contributed to quantitative synthesis. SGLT2 inhibitors reduced the composite of cardiovascular death or worsening HF (HR 0.77, 95% CI 0.72–0.82; I2 = 0%), HF hospitalisation (HR 0.72, 0.67–0.78), cardiovascular death (HR 0.88, 0.80–0.96) and all-cause death (HR 0.92, 0.86–0.99). The composite benefit was similar in HF with reduced ejection fraction (HR 0.74, 0.68–0.82) and in mildly reduced or preserved ejection fraction (HR 0.81, 0.74–0.88). Mortality reduction was clearer in reduced than in preserved ejection fraction. Serious adverse events were not increased. Conclusion: SGLT2 inhibitors reduce HF events irrespective of LVEF, with high-certainty evidence, supporting their use as foundational therapy across the ejection fraction spectrum.
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Bhatia et al. (2026) conducted a meta-analysis in Heart failure across the left ventricular ejection fraction spectrum (HFrEF, HFmrEF, and HFpEF) (n=22,477). SGLT2 inhibitors (dapagliflozin, empagliflozin, sotagliflozin) vs. Matching placebo on top of background guideline-directed medical therapy was evaluated on Composite of cardiovascular death or worsening heart failure (HF hospitalisation or urgent HF visit) (HR 0.77, 95% CI 0.72-0.82, p=<0.001). SGLT2 inhibitors reduced the composite of cardiovascular death or worsening heart failure by 23% (HR 0.77, 95% CI 0.72-0.82; P < 0.001) across the ejection fraction spectrum.
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