Sodium-Glucose Co-transporter-2 Inhibitors and Cardiac Function Parameters: A Network Meta-analysis and Trial Sequential Analysis of Randomized Clinical Trials.

Background: Sodium-glucose Co-transporter-2 Inhibitors (SGLT2is) are recommended for heart failure based on clinical outcomes. However, there is a lack of evidence linking SGLT2is with changes in cardiac function parameters.

Aim: This study aimed to systematically evaluate the literature assessing the impact of SGLT2is on various cardiac parameters.

Methods: Randomized clinical trials assessing any of the cardiac function parameters (atrial, valvular, pulmonary artery, and left ventricular) with SGLT2is were included. Mixed treatment comparison pooled estimates (mean differences (MD); 95% confidence intervals (95% CI)) were generated using a random-effects model and validated using trial sequential and bootstrap analyses. Intraclass differences and sub-group analysis in heart failure were evaluated.

Results: Thirty-four studies (2930 participants) were included in the review, of which 31 (2616 participants) were included in the meta-analysis. SGLT2is were associated with a significant increase in left ventricular ejection fraction (MD: 0.73; 95% CI: 0.09, 1.37%) and reductions in left ventricular mass (MD: -0.21; 95% CI: -0.39, -0.03 g), left ventricular mass index (MD: -0.22; 95% CI: - 0.36, -0.08 g/m2), left ventricular end-diastolic diameter (MD: -0.71; 95% CI: -1.29, -0.13 cm), left ventricular end-diastolic volume (MD: -0.56; 95% CI: -1.02, -0.1 ml), left atrial volume index (MD: -0.35; 95% CI: -0.58, -0.04 ml/m²), and pulmonary artery systolic pressure (MD: -1.08; 95% CI: - 1.94, -0.21 mmHg). Significant improvements in various cardiac parameters were observed in studies conducted on heart failure.

Conclusion: The findings of this study assessing cardiac function parameters support the guidelines recommending SGLT2 inhibitors in heart failure, which are primarily based on clinical outcomes.