Efficacy and Safety of SGLT2 Inhibitors and Sotagliflozin in Heart Failure: A Systematic Review and Meta-Analysis of 59 Randomized Controlled Trials
Abstract
Sodium-glucose cotransporter-2 (SGLT2) inhibitors have become a cornerstone of heart failure (HF) therapy, yet the totality of randomized evidence - including smaller trials beyond the landmark cardiovascular (CV) outcome studies - has not been comprehensively synthesized. We searched PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (ICTRP) from inception to March 2026 for randomized controlled trials (RCTs) comparing any SGLT2 inhibitor or the dual sodium-glucose cotransporter-1/2 (SGLT1/SGLT2) inhibitor sotagliflozin with placebo or standard care in adults with HF. Random-effects Mantel-Haenszel risk ratios (RRs) with Hartung-Knapp-Sidik-Jonkman (HKSJ) confidence intervals (CIs) were used. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. The protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD420251167908). Of 6,239 records identified, 114 studies met inclusion criteria and 59 RCTs (29,692 participants) were included in the quantitative synthesis. SGLT2 inhibitors reduced all-cause mortality (ACM; RR 0.90, 95% CI 0.83-0.98; p = 0.016; 26 trials; low certainty), although trim-and-fill adjustment for publication bias attenuated the finding (adjusted RR 0.92, 95% CI 0.84-1.00). HF hospitalization (HFH) was reduced…
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: 29,692 participants or records.
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