Cardiovascular protection by SGLT2 inhibitors – Do anti-inflammatory mechanisms play a role?
Background: Metabolic syndrome and related metabolic disturbances represent a state of low-grade inflammation, which accelerates insulin resistance, type 2 diabetes (T2D) and cardiovascular disease (CVD) progression. Among antidiabetic medications, sodium glucose co-transporter (SGLT) 2 inhibitors a...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877822001181 |
| _version_ | 1798003359427330048 |
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| author | Asmaa Elrakaybi Katharina Laubner Qian Zhou Martin J. Hug Jochen Seufert |
| author_facet | Asmaa Elrakaybi Katharina Laubner Qian Zhou Martin J. Hug Jochen Seufert |
| author_sort | Asmaa Elrakaybi |
| collection | DOAJ |
| description | Background: Metabolic syndrome and related metabolic disturbances represent a state of low-grade inflammation, which accelerates insulin resistance, type 2 diabetes (T2D) and cardiovascular disease (CVD) progression. Among antidiabetic medications, sodium glucose co-transporter (SGLT) 2 inhibitors are the only agents which showed remarkable reductions in heart failure (HF) hospitalizations and major cardiovascular endpoints (MACE) as well as renal endpoints regardless of diabetes status in large randomized clinical outcome trials (RCTs). Although the exact mechanisms underlying these benefits are yet to be established, growing evidence suggests that modulating inflammation by SGLT2 inhibitors may play a key role. Scope of review: In this manuscript, we summarize the current knowledge on anti-inflammatory effects of SGLT2 inhibitors as one of the mechanisms potentially mediating their cardiovascular (CV) benefits. We introduce the different metabolic and systemic actions mediated by these agents which could mitigate inflammation, and further present the signalling pathways potentially responsible for their proposed direct anti-inflammatory effects. We also discuss controversies surrounding some of these mechanisms. Major conclusions: SGLT2 inhibitors are promising anti-inflammatory agents by acting either indirectly via improving metabolism and reducing stress conditions or via direct modulation of inflammatory signalling pathways. These effects were achieved, to a great extent, in a glucose-independent manner which established their clinical use in HF patients with and without diabetes. |
| first_indexed | 2024-04-11T12:06:07Z |
| format | Article |
| id | doaj.art-85c52d85cf804909b920f6d3a5d49a23 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-04-11T12:06:07Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-85c52d85cf804909b920f6d3a5d49a232022-12-22T04:24:43ZengElsevierMolecular Metabolism2212-87782022-10-0164101549Cardiovascular protection by SGLT2 inhibitors – Do anti-inflammatory mechanisms play a role?Asmaa Elrakaybi0Katharina Laubner1Qian Zhou2Martin J. Hug3Jochen Seufert4Division of Endocrinology and Diabetology, Department of Medicine II, Medical Centre – University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; Department of Clinical Pharmacy, Ain Shams University, 11566 Cairo, EgyptDivision of Endocrinology and Diabetology, Department of Medicine II, Medical Centre – University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyDepartment of Cardiology and Angiology I, Heart Centre, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; Department of Cardiology, University Hospital Basel, 4031 Basel, SwitzerlandPharmacy, Medical Centre – University of Freiburg, 79106 Freiburg, GermanyDivision of Endocrinology and Diabetology, Department of Medicine II, Medical Centre – University of Freiburg, Faculty of Medicine, University of Freiburg, 79106 Freiburg, Germany; Corresponding author. Division of Endocrinology and Diabetology, Department of Medicine II, Medical Centre – University of Freiburg, Hugstetter Str. 55, 79106 Freiburg/Brsg, Germany.Background: Metabolic syndrome and related metabolic disturbances represent a state of low-grade inflammation, which accelerates insulin resistance, type 2 diabetes (T2D) and cardiovascular disease (CVD) progression. Among antidiabetic medications, sodium glucose co-transporter (SGLT) 2 inhibitors are the only agents which showed remarkable reductions in heart failure (HF) hospitalizations and major cardiovascular endpoints (MACE) as well as renal endpoints regardless of diabetes status in large randomized clinical outcome trials (RCTs). Although the exact mechanisms underlying these benefits are yet to be established, growing evidence suggests that modulating inflammation by SGLT2 inhibitors may play a key role. Scope of review: In this manuscript, we summarize the current knowledge on anti-inflammatory effects of SGLT2 inhibitors as one of the mechanisms potentially mediating their cardiovascular (CV) benefits. We introduce the different metabolic and systemic actions mediated by these agents which could mitigate inflammation, and further present the signalling pathways potentially responsible for their proposed direct anti-inflammatory effects. We also discuss controversies surrounding some of these mechanisms. Major conclusions: SGLT2 inhibitors are promising anti-inflammatory agents by acting either indirectly via improving metabolism and reducing stress conditions or via direct modulation of inflammatory signalling pathways. These effects were achieved, to a great extent, in a glucose-independent manner which established their clinical use in HF patients with and without diabetes.http://www.sciencedirect.com/science/article/pii/S2212877822001181SGLT2 inhibitorsInflammationMetabolismHeart failureCardiovascular disease |
| spellingShingle | Asmaa Elrakaybi Katharina Laubner Qian Zhou Martin J. Hug Jochen Seufert Cardiovascular protection by SGLT2 inhibitors – Do anti-inflammatory mechanisms play a role? Molecular Metabolism SGLT2 inhibitors Inflammation Metabolism Heart failure Cardiovascular disease |
| title | Cardiovascular protection by SGLT2 inhibitors – Do anti-inflammatory mechanisms play a role? |
| title_full | Cardiovascular protection by SGLT2 inhibitors – Do anti-inflammatory mechanisms play a role? |
| title_fullStr | Cardiovascular protection by SGLT2 inhibitors – Do anti-inflammatory mechanisms play a role? |
| title_full_unstemmed | Cardiovascular protection by SGLT2 inhibitors – Do anti-inflammatory mechanisms play a role? |
| title_short | Cardiovascular protection by SGLT2 inhibitors – Do anti-inflammatory mechanisms play a role? |
| title_sort | cardiovascular protection by sglt2 inhibitors do anti inflammatory mechanisms play a role |
| topic | SGLT2 inhibitors Inflammation Metabolism Heart failure Cardiovascular disease |
| url | http://www.sciencedirect.com/science/article/pii/S2212877822001181 |
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