Cardioprotective effect of a GLP-1 receptor agonist in insulin-resistant heart through improvements in Ca2+-homeostasis and mitochondrial function


Turan B.

9th EU-CARDIOPROTECTION COST Action Final MC/WG meeting , Coimbra, Portugal, 2 - 04 April 2022

  • Publication Type: Conference Paper / Unpublished
  • City: Coimbra
  • Country: Portugal
  • Lokman Hekim University Affiliated: Yes

Abstract

Heart failure (HF) is a leading cause of death and disability worldwide. As such, there is an urgent need to discover novel treatment targets that can reduce the risk of HF and improve clinical outcomes. The sodium glucose co-transporter 2 (SGLT2), which is selectively expressed in human kidney, plays a critical role in regulating glucose levels. SGLT2 is overactive in patients with type 2 diabetes mellitus (T2DM); hence, its inhibition has been proposed as a therapeutic strategy for alleviating hyperglycemia. Intriguingly, in addition to lowering glucose levels, SGLT2 inhibitors have been found to improve cardiovascular outcomes with primary effects on reducing hospitalization for HF in both T2DM and non-diabetic patients. The mechanisms underlying the cardiovascular protective effects of SGLT2 inhibitors remain unclear. The absence of SGLT2 in cardiomyocytes, albeit controversial, has prompted researchers to re-evaluate the mode of action of SGLT2 inhibitors. Several hypotheses have been proposed including the regulation of ketone body metabolism, restoration of ionic imbalances, improved mitochondrial function, and reduced inflammation, culminating in the restoration of cardiac function. In this review, we provide an overview of the clinical trials that have evaluated the use of SGLT2 inhibitors and discuss the potential mechanisms through which cardioprotection could be achieved. A deeper understanding of how SGLT2 inhibitors prevent HF could facilitate their rapid entry into routine clinical practice to improve health outcomes in HF patients.