Impact of SGLT2 inhibitors on cardiac function and infarct size in experimental myocardial ischemic injury: systematic literature review and meta-analysis

Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have been included in current clinical practice guidelines to decrease heart failure hospitalization or cardiovascular death, but further rigorous studies are necessary to determine the extent of their capacity for managing HF symptoms. We carried out a systematic literature review and meta-analysis to evaluate the impact of different SGLT2i on left ventricular ejection fraction (LVEF) and/or infarct size (IS) measured as the % of either the left ventricle (LV) or the area at risk (AAR) in animal models of myocardial infarction and ischemia–reperfusion injury. The study protocol was pre-registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42023427960). PubMed, Scopus and Web of Science databases were searched from inception to 15 May 2025. Primary endpoints were changes to LVEF and IS in treated versus control groups. Sixty-five studies with a total of 99 valid comparisons complying with the pre-defined inclusion criteria were identified. SGLT2i-treated animals exhibited a significantly improved LVEF (MD = 11.25% [95% CI 9.45, 13.05], p < 0.0001) and decreased IS both when measured as a %LV (MD = − 11.57% [95% CI − 14.96, − 8.18], p < 0.0001) or as a %AAR (MD = − 15.47% [95% CI − 19.03, − 11.91], p < 0.0001) compared to control subjects, independently of diabetic status. A sex-specific meta-analysis revealed a potentially greater LVEF improvement in males (MD = 12.08% [95% CI 10.14; 14.01]) than females (MD = 7.27% [95% CI 4.52; 10.03], p = 0.03). Dapagliflozin administration decreased IS as a %LV significantly more than empagliflozin (MD = − 15.99 [95% CI − 20.64, − 11.35] versus MD = − 4.14 [95% CI − 11.46, − 3.18], p = 0.013). In conclusion, the use of SGLT2i in animal models of ischemia improves LVEF irrespective of the SGLT2i used or the diabetic status of the subjects, significantly more in male animals, and consistently decreases IS.