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Evaluation of Cardiac Contractility Modulation Therapy in 2D Human Stem Cell-Derived Cardiomyocytes
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Sodium-glucose co-transporter 2 inhibitor therapy: mechanisms of action in heart failure

Shruti S Joshi1, Trisha Singh2, David E Newby2

  • 1BHF Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, UK sjoshi@ed.ac.uk.

Heart (British Cardiac Society)
|February 27, 2021
PubMed

Insights

Sodium-glucose co-transporter 2 (SGLT2) inhibitors benefit heart failure patients, even without diabetes. Research explores novel cardiac mechanisms beyond glucose control, including improved calcium handling and myocardial energetics.

Area of Science:

  • Cardiology
  • Endocrinology
  • Pharmacology

Background:

  • Type 2 diabetes mellitus (T2DM) patients face elevated heart failure (HF) risk.
  • Sodium-glucose co-transporter 2 (SGLT2) inhibitors improve glycemic control and reduce cardiovascular events in T2DM.
  • Remarkable cardiovascular benefits of SGLT2 inhibitors are observed in HF patients without T2DM, with unclear mechanisms.

Purpose of the Study:

  • To review cardiac-specific mechanisms of SGLT2 inhibitor action.
  • To highlight ongoing research into these proposed mechanisms.
  • To understand SGLT2 inhibitor benefits in cardiovascular health and disease.

Main Methods:

  • Literature review of landmark clinical trials and recent studies.
  • Analysis of proposed mechanistic pathways for SGLT2 inhibitor effects.
  • Identification of ongoing investigations into these mechanisms.

Main Results:

  • SGLT2 inhibitors demonstrate cardiovascular benefits beyond glycemic control.
  • Proposed mechanisms include improved cardiomyocyte calcium handling, enhanced myocardial energetics, autophagy induction, and reduced epicardial fat.
  • Existing explanations like diuresis, weight reduction, and blood pressure lowering do not fully account for clinical outcomes.

Conclusions:

  • Novel cardiac-specific mechanisms are crucial for understanding SGLT2 inhibitor efficacy in heart failure.
  • Further research is warranted to elucidate these pathways.
  • SGLT2 inhibitors represent a promising therapeutic strategy for cardiovascular protection.
Keywords:
heart failureheart failure with reduced ejection fractionpharmacologysystemic review

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