Investigation of mechanisms underpinning the effects of SGLT2 inhibition in heart failure

The impact of SGLT2 inhibition on reverse cardiac remodeling in patients with HF.<br>2. The effect of SGLT2 inhibition in patients with HF on novel and standard care biomarkers.<br>3. The effect of SGLT2 inhibition in patients with HF on proteomic expression.<br>The central clinical study was a 26-week, single-arm prospective evaluation of the effects of SGLT2 inhibition on cardiac biomarkers, proteomic shift, myocardial remodeling and patient reported outcomes in patients with heart failure.<br><br>Results<br>In this thesis by publication, across the collective series of papers presented, we have demonstrated that SGLT2 inhibition in patients with heart failure produces several notable effects.

In our meta-analysis we demonstrated SGLT2 inhibition promotes improvements in several cardiac imaging markers of reverse cardiac remodeling. Furthermore, in our clinical study, we found that SGLT2i suppresses markers associated with cardiac fibrosis and inflammation in addition to modulation of proteins/pathways involved in regulation of oxidative stress, cardiac repair, vascular homeostasis and autophagy.<br><br>Conclusion<br>These results add to the growing body of evidence that SGLT2i may promote cardiac remodeling via modulation of several pathways, distinct to conventional HF therapy.<br><br><i>Thesis embargoed until 31st July 2028.</i>