The Effects of SGLT2 Inhibition on Cardiac Function in Mice with Duchenne Muscular Dystrophy

Abstract

Background: Duchenne muscular dystrophy is a genetic condition that leads to progressive muscle deterioration and heart failure, primarily in young boys. This study aims to investigate the efficacy of empagliflozin, an SGLT2 inhibitor (SGLT2i) used to treat other causes of heart failure, in improving cardiac function in a mouse model of Duchenne muscular dystrophy. Methods: Three cohorts of mice, DMD mice treated with SGLT2i (MDX group, n=10), non-DMD mice treated with SGLT2i (DBA group, n=10), and DMD mice without treatment (MDX-ND, n=9) underwent cardiac imaging with high-frequency ultrasound at baseline, 4-, 7-, 12-, and 16-weeks. The drug was administered through the mice's food. Results: Preliminary 2D analysis showed normal left ventricular ejection fraction at baseline for all groups (MDX: 57.8 ± 15.6%, DBA: 54.0 ± 14.1%, MDX-ND: 68.5 ± 6.1%). At 16 weeks, the ejection fraction decreased in the MDX-ND group, while ejection fraction remained similar to baseline in the MDX and DBA groups (MDX: 50.4 ± 9.9%, DBA: 56.4 ± 6.7%, MDX-ND: 43.5 ± 9.0%). Conclusions: These preliminary results suggest that SGLT2i may slow the progression of cardiac dysfunction in DMD. These encouraging results justify further investigation with larger sample size and longer follow-up. Next steps include more in-depth analysis of cardiac function with 4D ultrasound cardiac data and/or more controlled drug delivery with injection.