In comparison to glucagon-like peptide-1 receptor agonists (GLP1-RA) and metformin, the superiority of sodium-glucose transporter 2 inhibitor (SGLT2i) was evident in improving left ventricular ejection fraction (LVEF) in heart failure (HF) with reduced ejection fraction patients, as well as improving maximal oxygen consumption (PVO ₂ ) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) in non-diabetic HF patients.

• This Bayesian network meta-analysis of seven randomized controlled trials involving 2897 patients was conducted to assess the effect of various glucose-lowering medications on the outcomes of non-diabetic HF patients.

• The most favorable medication in lowering NT-proBNP was SGLT2i, with the significant decrease in NT-proBNP vs GLP1-RA, metformin, and placebo.

• More effectiveness of SGLT2i was evident in improving LVEF for HF with reduced ejection fraction patients, vs GLP1-RA and placebo.

• Compared with placebo, more favourable were SGLT2i and GLP1-RA in improving PVO ₂ , with significant increase of PVO ₂ at a mean difference of 1.60 mL/kg/min and 0.86 mL/kg/min, respectively.

• All three drugs demonstrated comparable safety relative to placebo.