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Homogeneous Time-resolved Förster Resonance Energy Transfer-based Assay for Detection of Insulin Secretion
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SGLT2-inhibitors; more than just glycosuria and diuresis

Amir Fathi1, Keeran Vickneson2, Jagdeep S Singh3,4

  • 1Department of Neuroanaesthesia and Critical Care, National Hospital for Neurology and Neurosurgery, University College London, London, UK.

Heart Failure Reviews
|December 4, 2020
PubMed

Insights

Sodium-glucose linked cotransporter subtype 2 (SGLT2) inhibitors show cardiovascular benefits, particularly for heart failure (HF), irrespective of diabetes status. Current research explores novel mechanisms beyond their glucose-lowering effects to explain these findings.

Area of Science:

  • Cardiology
  • Endocrinology
  • Pharmacology

Background:

  • Heart failure (HF) poses a significant public health challenge, often exacerbated by comorbidities like type 2 diabetes mellitus (T2DM).
  • T2DM complicates HF management and limits treatment options.
  • Sodium-glucose linked cotransporter subtype 2 (SGLT2) inhibitors, initially for T2DM, demonstrate significant cardiovascular benefits, including improved HF outcomes, independent of glycemic control.

Purpose of the Study:

  • To review and discuss emerging hypotheses on the cardioprotective mechanisms of SGLT2 inhibitors.
  • To explore cutting-edge concepts beyond the established glycosuric and diuretic effects.
  • To understand the molecular mechanics underlying the observed clinical benefits of SGLT2 inhibitors in HF.

Main Methods:

  • Review of current scientific literature and clinical trial data.
  • Analysis of emerging mechanistic theories regarding SGLT2 inhibitor action.
  • Discussion of novel hypotheses on myocardial energetics, calcium balance, and renal physiology.

Main Results:

  • The primary mechanism of SGLT2 inhibition (glycosuria, diuresis) is unlikely to fully explain the rapid and substantial cardiovascular benefits observed.
  • Emerging theories suggest effects on myocardial energetics and calcium handling.
  • Renal physiological changes are also being investigated as potential contributors to the observed benefits.

Conclusions:

  • The precise mechanism of action for the cardiovascular benefits of SGLT2 inhibitors remains under investigation.
  • Novel molecular pathways, potentially involving cardiac metabolism and ion balance, are key areas of research.
  • Further elucidation of these mechanisms could lead to optimized therapeutic strategies for heart failure.

Keywords:
Calcium handlingHeart failureMyocardial energeticsRenal diseaseSGLT2-inhibitorsVentricular remodelling

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