Exploring the Cardiorenal Benefits of SGLT2i: A Comprehensive Review

The history of sodium-glucose cotransporter 2 inhibitors (SGLT2i) is so long and started in 1835 when Petersen extracted a compound called phlorizin from apple tree bark. About fifty years later, von Mering discovered its glucosuric properties. In the 1980s, it was discovered that the glucosuria res...

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Main Authors: Angelica Cersosimo, Andrea Drera, Marianna Adamo, Marco Metra, Enrico Vizzardi
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Kidney and Dialysis
Subjects:
Online Access:https://www.mdpi.com/2673-8236/4/4/16
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author Angelica Cersosimo
Andrea Drera
Marianna Adamo
Marco Metra
Enrico Vizzardi
author_facet Angelica Cersosimo
Andrea Drera
Marianna Adamo
Marco Metra
Enrico Vizzardi
author_sort Angelica Cersosimo
collection DOAJ
description The history of sodium-glucose cotransporter 2 inhibitors (SGLT2i) is so long and started in 1835 when Petersen extracted a compound called phlorizin from apple tree bark. About fifty years later, von Mering discovered its glucosuric properties. In the 1980s, it was discovered that the glucosuria resulted from inhibition by phlorizin of glucose reabsorption by the renal tubules, which lowered blood glucose levels in diabetic rats. Nowadays, beyond their glucose-lowering effects, growing evidence suggests significant cardiorenal benefits associated with SGLT2i therapy. Indeed, several clinical trials, including landmark studies such as EMPA-REG OUTCOME, CANVAS Program, and DECLARE-TIMI 58, have demonstrated robust reductions in cardiovascular events, particularly heart failure hospitalizations and cardiovascular mortality, among patients treated with SGLT2i. However, subsequent trials showed that SGLT2i benefits extend beyond the diabetic population, encompassing individuals with and without diabetes. Additionally, SGLT2i exhibit nephroprotective effects, manifesting as a slowing of the progression of chronic kidney disease and a reduction in the risk of end-stage kidney disease. The mechanisms underlying the cardiorenal benefits of SGLT2i are multifactorial and include improvements in glycemic control, reduction in arterial stiffness, modulation of inflammation and oxidative stress, reduction of intraglomerular pression and promotion of natriuresis and diuresis through inhibition of SGLT2 in the luminal brush border of the first segments of the proximal kidney tubule. This narrative review aims to explore the cardiorenal outcomes of SGLT2i, encompassing their mechanisms of action, clinical evidence, safety profile, and implications for clinical practice.
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spelling doaj-art-eeacb85681b849f3a720bcf34efc6cdf2024-12-27T14:34:41ZengMDPI AGKidney and Dialysis2673-82362024-10-014418420210.3390/kidneydial4040016Exploring the Cardiorenal Benefits of SGLT2i: A Comprehensive ReviewAngelica Cersosimo0Andrea Drera1Marianna Adamo2Marco Metra3Enrico Vizzardi4Department of Medical and Surgical Specialties, Institute of Cardiology, University of Brescia, 25123 Brescia, ItalyDepartment of Medical and Surgical Specialties, Institute of Cardiology, University of Brescia, 25123 Brescia, ItalyDepartment of Medical and Surgical Specialties, Institute of Cardiology, University of Brescia, 25123 Brescia, ItalyDepartment of Medical and Surgical Specialties, Institute of Cardiology, University of Brescia, 25123 Brescia, ItalyDepartment of Medical and Surgical Specialties, Institute of Cardiology, University of Brescia, 25123 Brescia, ItalyThe history of sodium-glucose cotransporter 2 inhibitors (SGLT2i) is so long and started in 1835 when Petersen extracted a compound called phlorizin from apple tree bark. About fifty years later, von Mering discovered its glucosuric properties. In the 1980s, it was discovered that the glucosuria resulted from inhibition by phlorizin of glucose reabsorption by the renal tubules, which lowered blood glucose levels in diabetic rats. Nowadays, beyond their glucose-lowering effects, growing evidence suggests significant cardiorenal benefits associated with SGLT2i therapy. Indeed, several clinical trials, including landmark studies such as EMPA-REG OUTCOME, CANVAS Program, and DECLARE-TIMI 58, have demonstrated robust reductions in cardiovascular events, particularly heart failure hospitalizations and cardiovascular mortality, among patients treated with SGLT2i. However, subsequent trials showed that SGLT2i benefits extend beyond the diabetic population, encompassing individuals with and without diabetes. Additionally, SGLT2i exhibit nephroprotective effects, manifesting as a slowing of the progression of chronic kidney disease and a reduction in the risk of end-stage kidney disease. The mechanisms underlying the cardiorenal benefits of SGLT2i are multifactorial and include improvements in glycemic control, reduction in arterial stiffness, modulation of inflammation and oxidative stress, reduction of intraglomerular pression and promotion of natriuresis and diuresis through inhibition of SGLT2 in the luminal brush border of the first segments of the proximal kidney tubule. This narrative review aims to explore the cardiorenal outcomes of SGLT2i, encompassing their mechanisms of action, clinical evidence, safety profile, and implications for clinical practice.https://www.mdpi.com/2673-8236/4/4/16SGLT2 inhibitorsdiabetes mellituschronic kidney diseasecardiovascular diseaseheart failure
spellingShingle Angelica Cersosimo
Andrea Drera
Marianna Adamo
Marco Metra
Enrico Vizzardi
Exploring the Cardiorenal Benefits of SGLT2i: A Comprehensive Review
Kidney and Dialysis
SGLT2 inhibitors
diabetes mellitus
chronic kidney disease
cardiovascular disease
heart failure
title Exploring the Cardiorenal Benefits of SGLT2i: A Comprehensive Review
title_full Exploring the Cardiorenal Benefits of SGLT2i: A Comprehensive Review
title_fullStr Exploring the Cardiorenal Benefits of SGLT2i: A Comprehensive Review
title_full_unstemmed Exploring the Cardiorenal Benefits of SGLT2i: A Comprehensive Review
title_short Exploring the Cardiorenal Benefits of SGLT2i: A Comprehensive Review
title_sort exploring the cardiorenal benefits of sglt2i a comprehensive review
topic SGLT2 inhibitors
diabetes mellitus
chronic kidney disease
cardiovascular disease
heart failure
url https://www.mdpi.com/2673-8236/4/4/16
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