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\begin{document}

\title{Cardiovascular outcomes and molecular targets for the cardiac effects of
Sodium-Glucose Cotransporter 2 Inhibitors: A systematic review}



\author[1]{Rosalinda Madonna}%
\author[1]{Filippo Biondi}%
\author[1]{Mattia Alberti}%
\author[1]{Sandra Ghelardoni}%
\author[1]{Letizia Mattii}%
\author[2]{Alberto D'Alleva}%
\affil[1]{University of Pisa}%
\affil[2]{Gabriele d'Annunzio University of Chieti and Pescara Department of Sciences}%


\vspace{-1em}



  
  \date{May 21, 2024}


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\begin{abstract}
Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new class of
glucose-lowering drugs traditionally used to control blood glucose
levels in patients with type 2 diabetes mellitus, have been proven to
reduce major adverse cardiovascular events, including cardiovascular
death, in patients with heart failure irrespective of ejection fraction
and independently of the hypoglycemic effect. Because of their favorable
effects on the kidney and cardiovascular outcomes, their use has been
expanded in all patients with any combination of diabetes mellitus type
2, chronic kidney disease and heart failure. Although mechanisms
explaining the effects of these drugs on the cardiovascular system are
not well understood, their effectiveness in all these conditions
suggests that they act at the intersection of the metabolic, renal and
cardiac axes, thus disrupting maladaptive vicious cycles while
contrasting direct organ damage. In this systematic review we provide a
state of the art of the randomized controlled trials investigating the
effect of SGLT2i on cardiovascular outcomes in patients with chronic
kidney disease and/or heart failure irrespective of ejection fraction
and diabetes. We also discuss the molecular targets and signaling
pathways potentially explaining the cardiac effects of these
pharmacological agents, from a clinical and experimental perspective.%
\end{abstract}%



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