SGLT2 Inhibitors Improve Skeletal Muscle Pathology in Heart Failure, reveals study

The key findings of the study were:

• Patients receiving SGLT2 inhibitors (SGLT2i) showed a significant reduction of approximately 20% in myofiber atrophy compared to untreated patients (p = 0.07).

• Analysis revealed a distinct transcriptomic signature in SGLT2i-treated patients, associated with beneficial effects on muscle atrophy, metabolism, and inflammation.

• Metabolomic profiling showed notable changes in tryptophan metabolism, with a 24% increase in kynurenic acid and a 32% decrease in kynurenine levels in SGLT2i-treated patients (p < 0.001).

• SGLT2i treatment led to reduced levels of pro-inflammatory cytokines by 26–64%, alongside modulation of downstream muscle interleukin-6-JAK/STAT3 signaling (p < 0.05).

• Experiments in mice treated with SGLT2 inhibitors demonstrated improvements in muscle pathology, supporting the clinical findings and indicating a conserved mammalian response to treatment.

The study suggests that treatment with SGLT2i influences skeletal muscle pathology in HFrEF patients, leading to anti-atrophic, anti-inflammatory, and pro-metabolic effects. These changes may be mediated through IL-6–kynurenine signaling. Improved skeletal muscle health may contribute to the clinical benefits of SGLT2i in HFrEF management.

The findings highlight the potential of SGLT2i as therapeutic agents not only for cardiac outcomes but also for improving skeletal muscle health in HFrEF patients. Further research is warranted to optimize treatment protocols and better understand the underlying mechanisms.

Reference:

Wood, N., Straw, S., Cheng, C. W., Hirata, Y., Pereira, M. G., Gallagher, H., Egginton, S., Ogawa, W., Wheatcroft, S. B., Witte, K. K., Roberts, L. D., & Bowen, T. S. (2024). Sodium–glucose cotransporter 2 inhibitors influence skeletal muscle pathology in patients with heart failure and reduced ejection fraction. European Journal of Heart Failure. https://doi.org/10.1002/ejhf.3192