Exploring the disconnect: mechanisms underpinning the absence of physical function improvement with SGLT2 inhibitors
Current evidence suggests sodium-glucose cotransporter 2 inhibitors (SGLT2i) do not consistently improve patient physical function, despite improvements in clinical symptoms and reductions in both adiposity and body weight. We highlight heterogenous methodologies in SGLT2i physical function trials....
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| Language: | English |
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Frontiers Media S.A.
2025-05-01
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| Series: | Frontiers in Systems Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fsysb.2025.1593229/full |
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| author | Cian Sutcliffe Cian Sutcliffe Jack A. Sargeant Jack A. Sargeant Thomas Yates Thomas Yates Melanie J. Davies Melanie J. Davies Luke A. Baker Luke A. Baker |
| author_facet | Cian Sutcliffe Cian Sutcliffe Jack A. Sargeant Jack A. Sargeant Thomas Yates Thomas Yates Melanie J. Davies Melanie J. Davies Luke A. Baker Luke A. Baker |
| author_sort | Cian Sutcliffe |
| collection | DOAJ |
| description | Current evidence suggests sodium-glucose cotransporter 2 inhibitors (SGLT2i) do not consistently improve patient physical function, despite improvements in clinical symptoms and reductions in both adiposity and body weight. We highlight heterogenous methodologies in SGLT2i physical function trials. We then provide context to these findings by collating new data which describes how reduced glycaemia with SGLT2i alters numerous physiological processes and discuss how these alterations may diminish or prevent expected functional improvements. Alterations include changes to energy homeostasis, pancreatic hormones, muscle metabolism, physical activity, and appetite regulation. Current evidence in humans is limited and the mechanistic interaction between SGLT2i, skeletal muscle, and physical function remains incompletely understood. Future investigations must embed comprehensive molecular techniques within suitably designed clinical trials to determine how skeletal muscle health and patient mobility is influenced by acute and long term SGLT2i prescription. |
| format | Article |
| id | doaj-art-d60a549489384fb9b65a9bebd33aeff7 |
| institution | OA Journals |
| issn | 2674-0702 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Systems Biology |
| spelling | doaj-art-d60a549489384fb9b65a9bebd33aeff72025-08-20T02:17:08ZengFrontiers Media S.A.Frontiers in Systems Biology2674-07022025-05-01510.3389/fsysb.2025.15932291593229Exploring the disconnect: mechanisms underpinning the absence of physical function improvement with SGLT2 inhibitorsCian Sutcliffe0Cian Sutcliffe1Jack A. Sargeant2Jack A. Sargeant3Thomas Yates4Thomas Yates5Melanie J. Davies6Melanie J. Davies7Luke A. Baker8Luke A. Baker9Department of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, United KingdomDiabetes Research Centre, University of Leicester, Leicester, United KingdomDiabetes Research Centre, University of Leicester, Leicester, United KingdomNational Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, United KingdomDiabetes Research Centre, University of Leicester, Leicester, United KingdomNational Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, United KingdomDiabetes Research Centre, University of Leicester, Leicester, United KingdomNational Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, United KingdomDepartment of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, United KingdomNational Institute for Health Research (NIHR) Leicester Biomedical Research Centre, Leicester, United KingdomCurrent evidence suggests sodium-glucose cotransporter 2 inhibitors (SGLT2i) do not consistently improve patient physical function, despite improvements in clinical symptoms and reductions in both adiposity and body weight. We highlight heterogenous methodologies in SGLT2i physical function trials. We then provide context to these findings by collating new data which describes how reduced glycaemia with SGLT2i alters numerous physiological processes and discuss how these alterations may diminish or prevent expected functional improvements. Alterations include changes to energy homeostasis, pancreatic hormones, muscle metabolism, physical activity, and appetite regulation. Current evidence in humans is limited and the mechanistic interaction between SGLT2i, skeletal muscle, and physical function remains incompletely understood. Future investigations must embed comprehensive molecular techniques within suitably designed clinical trials to determine how skeletal muscle health and patient mobility is influenced by acute and long term SGLT2i prescription.https://www.frontiersin.org/articles/10.3389/fsysb.2025.1593229/fullSGLT2 (sodium-glucose cotransporter 2) inhibitorGlucagon-like peptide 1 (GLP-1) receptor agonistphysical functionskeletal muscleglucose lowering medicationmobility and ageing |
| spellingShingle | Cian Sutcliffe Cian Sutcliffe Jack A. Sargeant Jack A. Sargeant Thomas Yates Thomas Yates Melanie J. Davies Melanie J. Davies Luke A. Baker Luke A. Baker Exploring the disconnect: mechanisms underpinning the absence of physical function improvement with SGLT2 inhibitors Frontiers in Systems Biology SGLT2 (sodium-glucose cotransporter 2) inhibitor Glucagon-like peptide 1 (GLP-1) receptor agonist physical function skeletal muscle glucose lowering medication mobility and ageing |
| title | Exploring the disconnect: mechanisms underpinning the absence of physical function improvement with SGLT2 inhibitors |
| title_full | Exploring the disconnect: mechanisms underpinning the absence of physical function improvement with SGLT2 inhibitors |
| title_fullStr | Exploring the disconnect: mechanisms underpinning the absence of physical function improvement with SGLT2 inhibitors |
| title_full_unstemmed | Exploring the disconnect: mechanisms underpinning the absence of physical function improvement with SGLT2 inhibitors |
| title_short | Exploring the disconnect: mechanisms underpinning the absence of physical function improvement with SGLT2 inhibitors |
| title_sort | exploring the disconnect mechanisms underpinning the absence of physical function improvement with sglt2 inhibitors |
| topic | SGLT2 (sodium-glucose cotransporter 2) inhibitor Glucagon-like peptide 1 (GLP-1) receptor agonist physical function skeletal muscle glucose lowering medication mobility and ageing |
| url | https://www.frontiersin.org/articles/10.3389/fsysb.2025.1593229/full |
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