Effects of Sodium–Glucose Cotransporter 2 Inhibitors on Calcium Homeostasis: Where We Stand Now

Diabetes mellitus has been knowingly associated with increased risk of fractures, so much so that skeletal fragility is considered a complication of diabetes. Determinants of bone fragility in this chronic condition are several, and the diabetes treatment choice could influence bone metabolism. Sodi...

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Main Authors: Alessandro Cuttone, Anastasia Xourafa, Carmela Morace, Vittorio Cannavò, Francesca Maria Bueti, Giuseppe Mandraffino, Giovanni Squadrito, Giorgio Basile, Agostino Gaudio, Antonino Catalano, Giuseppina Tiziana Russo, Federica Bellone
Format: Article
Language:English
Published: MDPI AG 2025-05-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/10/724
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author Alessandro Cuttone
Anastasia Xourafa
Carmela Morace
Vittorio Cannavò
Francesca Maria Bueti
Giuseppe Mandraffino
Giovanni Squadrito
Giorgio Basile
Agostino Gaudio
Antonino Catalano
Giuseppina Tiziana Russo
Federica Bellone
author_facet Alessandro Cuttone
Anastasia Xourafa
Carmela Morace
Vittorio Cannavò
Francesca Maria Bueti
Giuseppe Mandraffino
Giovanni Squadrito
Giorgio Basile
Agostino Gaudio
Antonino Catalano
Giuseppina Tiziana Russo
Federica Bellone
author_sort Alessandro Cuttone
collection DOAJ
description Diabetes mellitus has been knowingly associated with increased risk of fractures, so much so that skeletal fragility is considered a complication of diabetes. Determinants of bone fragility in this chronic condition are several, and the diabetes treatment choice could influence bone metabolism. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have recently expanded the therapeutic armamentarium for type 2 diabetes mellitus (T2D); these antihyperglycemic drugs act by reducing renal glucose reabsorption in the proximal tubule and have a proven cardiorenal benefit. The role of SGLT2i towards phospho-calcium metabolism is still unclear, so we aimed to review the current evidence of the relationship between SGLT2i and calcium and phosphate homeostasis. The PubMed, Scopus, and Web of Knowledge databases were searched to identify original research articles, meta-analyses, and scientific reviews on effects on bone metabolism in T2D patients treated with SGLT2i. Emerging data indicate that SGLT2i may lead to a rise of bone turnover markers, promoting a lower skeletal bone density and an increased fracture risk on murine models, but in real-world studies, results are controversial. Therefore, more clinical trials are needed to further clarify this topic, and the effects of SGLT2i on calcium homeostasis remain to date poorly understood.
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spelling doaj-art-a6c666bc4edc4d689c1c2e26890dfa8b2025-08-20T03:47:53ZengMDPI AGCells2073-44092025-05-01141072410.3390/cells14100724Effects of Sodium–Glucose Cotransporter 2 Inhibitors on Calcium Homeostasis: Where We Stand NowAlessandro Cuttone0Anastasia Xourafa1Carmela Morace2Vittorio Cannavò3Francesca Maria Bueti4Giuseppe Mandraffino5Giovanni Squadrito6Giorgio Basile7Agostino Gaudio8Antonino Catalano9Giuseppina Tiziana Russo10Federica Bellone11Unit of Internal Medicine, Department of Clinical and Experimental Medicine, University Hospital G. Martino, University of Messina, 98100 Messina, ItalyUnit of Thalassemia, Policlinico “G. Rodolico”, Via S. Sofia 78, 95123 Catania, ItalyUnit of Internal Medicine, Department of Clinical and Experimental Medicine, University Hospital G. Martino, University of Messina, 98100 Messina, ItalyUnit of Internal Medicine, Department of Clinical and Experimental Medicine, University Hospital G. Martino, University of Messina, 98100 Messina, ItalyUnit of Internal Medicine, Department of Clinical and Experimental Medicine, University Hospital G. Martino, University of Messina, 98100 Messina, ItalyUnit of Internal Medicine, Department of Clinical and Experimental Medicine, University Hospital G. Martino, University of Messina, 98100 Messina, ItalyUnit of Internal Medicine, Department of Clinical and Experimental Medicine, University Hospital G. Martino, University of Messina, 98100 Messina, ItalyUnit of Geriatrics, Department of Biomedical and Dental Science and Morphofunctional Imaging, University Hospital G. Martino, University of Messina, 98100 Messina, ItalyUnit of Internal Medicine, Department of Clinical and Experimental Medicine, University of Catania, Policlinico “G. Rodolico”, 95123 Catania, ItalyUnit of Geriatrics, Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, ItalyUnit of Internal Medicine, Department of Clinical and Experimental Medicine, University Hospital G. Martino, University of Messina, 98100 Messina, ItalyUnit of Internal Medicine, Department of Clinical and Experimental Medicine, University Hospital G. Martino, University of Messina, 98100 Messina, ItalyDiabetes mellitus has been knowingly associated with increased risk of fractures, so much so that skeletal fragility is considered a complication of diabetes. Determinants of bone fragility in this chronic condition are several, and the diabetes treatment choice could influence bone metabolism. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have recently expanded the therapeutic armamentarium for type 2 diabetes mellitus (T2D); these antihyperglycemic drugs act by reducing renal glucose reabsorption in the proximal tubule and have a proven cardiorenal benefit. The role of SGLT2i towards phospho-calcium metabolism is still unclear, so we aimed to review the current evidence of the relationship between SGLT2i and calcium and phosphate homeostasis. The PubMed, Scopus, and Web of Knowledge databases were searched to identify original research articles, meta-analyses, and scientific reviews on effects on bone metabolism in T2D patients treated with SGLT2i. Emerging data indicate that SGLT2i may lead to a rise of bone turnover markers, promoting a lower skeletal bone density and an increased fracture risk on murine models, but in real-world studies, results are controversial. Therefore, more clinical trials are needed to further clarify this topic, and the effects of SGLT2i on calcium homeostasis remain to date poorly understood.https://www.mdpi.com/2073-4409/14/10/724diabetes mellitusSGLT2 inhibitorsempagliflozincanagliflozindapagliflozinertugliflozin
spellingShingle Alessandro Cuttone
Anastasia Xourafa
Carmela Morace
Vittorio Cannavò
Francesca Maria Bueti
Giuseppe Mandraffino
Giovanni Squadrito
Giorgio Basile
Agostino Gaudio
Antonino Catalano
Giuseppina Tiziana Russo
Federica Bellone
Effects of Sodium–Glucose Cotransporter 2 Inhibitors on Calcium Homeostasis: Where We Stand Now
Cells
diabetes mellitus
SGLT2 inhibitors
empagliflozin
canagliflozin
dapagliflozin
ertugliflozin
title Effects of Sodium–Glucose Cotransporter 2 Inhibitors on Calcium Homeostasis: Where We Stand Now
title_full Effects of Sodium–Glucose Cotransporter 2 Inhibitors on Calcium Homeostasis: Where We Stand Now
title_fullStr Effects of Sodium–Glucose Cotransporter 2 Inhibitors on Calcium Homeostasis: Where We Stand Now
title_full_unstemmed Effects of Sodium–Glucose Cotransporter 2 Inhibitors on Calcium Homeostasis: Where We Stand Now
title_short Effects of Sodium–Glucose Cotransporter 2 Inhibitors on Calcium Homeostasis: Where We Stand Now
title_sort effects of sodium glucose cotransporter 2 inhibitors on calcium homeostasis where we stand now
topic diabetes mellitus
SGLT2 inhibitors
empagliflozin
canagliflozin
dapagliflozin
ertugliflozin
url https://www.mdpi.com/2073-4409/14/10/724
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