Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors in Non-diabetic Heart Failure: A Systematic Review of Randomized Controlled Trials and Real-World Evidence
Abstract
Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were initially developed to improve glycemic control in patients with type 2 diabetes. More recently, growing evidence has highlighted their cardiovascular benefits, particularly in patients with heart failure (HF), irrespective of diabetic status. This systematic review evaluates the efficacy and safety of SGLT2i, including dapagliflozin and empagliflozin, in non-diabetic patients with HF across different phenotypes, namely heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). A comprehensive literature search was conducted in PubMed, Scopus, and Embase for studies published between January 1, 2015, and January 15, 2024, in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies included adult patients with HF, reported outcomes for non-diabetic subgroups, and assessed treatment with SGLT2i. Six studies met the inclusion criteria: four randomized controlled trials (RCTs), one pooled patient-level analysis, and one observational cohort study involving 16,264 non-diabetic patients. A pooled patient-level analysis incorporated data from DAPA-HF and DELIVER; to avoid duplication, only DAPA-HF was analyzed individually, while DELIVER was included solely within the pooled dataset. SGLT2i use was associated with lower cardiovascular mortality (hazard ratio (HR): 0.73-0.86) and reduced HF hospitalization, with consistent…
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Evidence Hub reads this as a systematic review, 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.
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