Efficacy and Safety of Sodium-Glucose Cotransporter-2 Inhibitors for Heart Failure in Children and Adolescents: A Single-Arm and Pairwise Systematic Review and Meta-Analysis with GRADE Assessment of the Evidence
Abstract
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a cornerstone of adult heart failure (HF) therapy and are increasingly prescribed off-label to children, yet pediatric outcomes have never been pooled. We searched PubMed/MEDLINE, Embase, Scopus, and Web of Science to 14 August 2026 for studies of any SGLT2 inhibitor in children or adolescents with HF and performed a single-arm meta-analysis of all exposed patients and a pairwise meta-analysis of the comparative studies with random-effects models. Nine studies contributed 599 exposed patients and 97 controls. Pooled rates were 3.8% (95% confidence interval [CI] 1.6-8.4) for mortality, 8.5% (6.2-11.5) for transplantation, 11.2% (8.2-15.1) for worsening HF, 0.2% (0.03-1.6) for ketoacidosis, 4.5% (1.2-14.9) for acute kidney injury, 3.7% (1.1-11.7) for urinary tract infection, and 4.1% (1.4-11.2) for discontinuation because of an adverse event. After initiation, left ventricular ejection fraction rose by 7.7 percentage points (3.6-11.8) and natriuretic peptide fell by 0.42 standard deviations (0.34-0.49). In the comparative synthesis (63 exposed, 97 unexposed), risk ratios were 0.80 (0.11-6.07) for mortality and 0.21 (0.03-1.68) for worsening HF; ejection fraction improved 3.34 percentage points more with SGLT2 inhibitors (0.22-6.46) whereas natriuretic peptide did not differ (standardized mean difference -0.09, -0.50 to 0.33).
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 599 participants or records.
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