Pathophysiological basis of the cardiological benefits of SGLT-2 inhibitors: a narrative review

Cardiovascular Diabetology

Review

Cristina Panico¹  Benedetta Bonora²  Maurizio Rondinelli³  Basilio Pintaudi⁴  Antonella Camera⁵  Nino Cristiano Chilelli⁶  Giuliana Da Prato⁷  Valeria Grancini⁸  Veronica Resi⁸  Emanuela Zarra⁹  Giuseppe Favacchio^1,10 

[1] Department of Biomedical Sciences, Humanitas University, Pieve Emanuele-Milan, Italy;IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy;Department of Medicine, Division of Metabolic Diseases, University of Padova, Via Giustiniani 2, 35128, Padua, Italy;Diabetes Endocrine and Metabolic Diseases Unit, IRCCS Centro Cardiologico Monzino, Milan, Italy;Diabetes Unit, Niguarda Hospital, Milan, Italy;Diabetologia, ASST Pavia, Padua, Italy;Diabetology and Internal Medicine, Hospital of Cittadella, AULSS 6 Euganea (Padua), Padua, Italy;Divisione di Endocrinologia, Diabetologia e Malattie del Metabolismo, Dipartimento di Medicina, Azienda Ospedaliera Universitaria Integrata di Verona, Ospedale Maggiore, Verona, Italy;Endocrinology Unit, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico, Milan, Italy;S.C. Medicina Diabetologia, Dipartimento di Continuità di Cura e Fragilità, ASST Spedali Civili, Brescia, Italy;U.O di Endocrinologia e Diabetologia, IRCCS Humanitas Research Hospital, Rozzano, MI, Italy;

关键词: SGLT2 inhibitors;    Type 2 diabetes;    Cardiovascular;    Mechanism of action;    Pathophysiology;    Heart failure;   

DOI  :  10.1186/s12933-023-01855-y

 received in 2023-02-23, accepted in 2023-05-10,  发布年份 2023

来源: Springer

【 摘 要 】

In recent years, GLP-1 receptor agonists (GLP-1RA), and SGLT-2 inhibitors (SGLT-2i) have become available, which have become valuable additions to therapy for type 2 diabetes as they are associated with low risk for hypoglycemia and cardiovascular benefits. Indeed, SGLT-2i have emerged as a promising class of agents to treat heart failure (HF). By inhibiting SGLT-2, these agents lead to excretion of glucose in urine with subsequent lowering of plasma glucose, although it is becoming clear that the observed benefits in HF cannot be explained by glucose-lowering alone. In fact, multiple mechanisms have been proposed to explain the cardiovascular and renal benefits of SGLT-2i, including hemodynamic, anti-inflammatory, anti-fibrotic, antioxidant, and metabolic effects. Herein, we review the available evidence on the pathophysiology of the cardiological benefits of SGLT-2i. In diabetic heart disease, in both clinical and animal models, the effect of SGLT-2i have been shown to improve diastolic function, which is even more evident in HF with preserved ejection fraction. The probable pathogenic mechanisms likely involve damage from free radicals, apoptosis, and inflammation, and therefore fibrosis, many of which have been shown to be improved by SGLT-2i. While the effects on systolic function in models of diabetic heart disease and HF with preserved ejection fraction is limited and contrasting, it is a key element in patients with HF and reduced ejection fraction both with and without diabetes. The significant improvement in systolic function appears to lead to subsequent structural remodeling of the heart with a reduction in left ventricle volume and a consequent reduction in pulmonary pressure. While the effects on cardiac metabolism and inflammation appear to be consolidated, greater efforts are still warranted to further define the entity to which these mechanisms contribute to the cardiovascular benefits of SGLT-2i.

【 授权许可】

CC BY   
© The Author(s) 2023