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  • SGLT2 Inhibitors...

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

Written By : Dr Riya Dave |Medically Reviewed By : Dr. Kamal Kant Kohli Published On 2024-04-01T19:45:55+05:30  |  Updated On 2 April 2024 10:54 AM IST
SGLT2 Inhibitors Improve Skeletal Muscle Pathology in Heart Failure, reveals study
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Patients with heart failure and reduced ejection fraction (HFrEF) often experience skeletal muscle pathology, contributing to symptoms and reduced quality of life. While sodium–glucose cotransporter 2 inhibitors (SGLT2i) have shown clinical benefits in HFrEF, their effects on skeletal muscle remain unclear. A recent study aimed to investigate whether SGLT2i influences skeletal muscle pathology in patients with HFrEF.


HFrEF patients commonly exhibit skeletal muscle abnormalities, exacerbating their condition. SGLT2i have emerged as promising treatments for HFrEF, yet their precise mechanisms of action are not fully understood. This study sought to elucidate the impact of SGLT2i on skeletal muscle health in HFrEF patients.

The study was published in the European Journal Of Heart Failure. The study was conducted by Nathanael Wood and colleagues. The study analyzed muscle biopsies from 28 male HFrEF patients treated with or without SGLT2i. Comprehensive analyses, including immunohistochemistry, transcriptomics, metabolomics, and serum inflammatory profiling, were conducted. Additionally, experiments in mice treated with SGLT2i were performed to validate findings.

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


European Journal Of Heart FailureSGLT2 inhibitorsheart failureskeletal muscle pathologyHFrEFtranscriptomemetabolomeinflammationclinical outcomes
Source : European Journal Of Heart Failure
Dr Riya Dave
Dr Riya Dave

    Dr Riya Dave has completed dentistry from Gujarat University in 2022. She is a dentist and accomplished medical and scientific writer known for her commitment to bridging the gap between clinical expertise and accessible healthcare information. She has been actively involved in writing blogs related to health and wellness.

    Dr. Kamal Kant Kohli
    Dr. Kamal Kant Kohli

    Dr Kamal Kant Kohli-MBBS, DTCD- a chest specialist with more than 30 years of practice and a flair for writing clinical articles, Dr Kamal Kant Kohli joined Medical Dialogues as a Chief Editor of Medical News. Besides writing articles, as an editor, he proofreads and verifies all the medical content published on Medical Dialogues including those coming from journals, studies,medical conferences,guidelines etc. Email: drkohli@medicaldialogues.in. Contact no. 011-43720751

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