Evidence map›Paper›PMID 42578286›Full record

ArticleCardiovascular research2026

Dual inhibition of SGLT 1 and 2 by sotagliflozin alleviates intracellular sodium overload and improves cardiometabolic remodelling in uraemic cardiomyopathy.

Megan Young, Anja Karlstaedt, Sanushi Dambure, Jack J J J Miller, Tong Guo, Xin Zhou, Zenouska Ramchunder, Jair Gonzalez Marques Junior, Muriel Nobles, Andrew Tinker and 13 more

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In one paragraph

Article in Cardiovascular research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors.

Megan YoungWilliam Harvey Research Institute, John Vane Science Centre, Barts and the London Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.ORCID 0009-0006-2178-3755
Anja KarlstaedtDepartment of Cardiology, Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, USA.
Sanushi DambureWilliam Harvey Research Institute, John Vane Science Centre, Barts and the London Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Jack J J J MillerThe MR Research Centre and The PET Centre, Clinical Medicine, Aarhus University, Aarhus 8200, Denmark.
Tong GuoWilliam Harvey Research Institute, John Vane Science Centre, Barts and the London Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Xin ZhouDepartment of Computer Science, University of Oxford, Oxford, UK.
Zenouska RamchunderWilliam Harvey Research Institute, John Vane Science Centre, Barts and the London Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Jair Gonzalez Marques JuniorCancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Muriel NoblesWilliam Harvey Research Institute, John Vane Science Centre, Barts and the London Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Andrew TinkerWilliam Harvey Research Institute, John Vane Science Centre, Barts and the London Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.ORCID 0000-0001-7703-4151
Kyuongmin KimDepartment of Cardiology, Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, USA.
Amanda R PurcellUniversity of Sydney, Faculty of Medicine and Health, Sydney, NSW, Australia.
Sarah J GlastrasUniversity of Sydney, Faculty of Medicine and Health, Sydney, NSW, Australia.
Fenn CullenWilliam Harvey Research Institute, John Vane Science Centre, Barts and the London Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Thomas R EykynSchool of Biomedical Engineering and Imaging Sciences, King's College London, St Thomas' Hospital, London, UK.
Alex Von KriegsheimCancer Research UK Scotland Centre, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.
Blanca RodriguezDepartment of Computer Science, University of Oxford, Oxford, UK.
Michelangelo CampanellaWilliam Harvey Research Institute, John Vane Science Centre, Barts and the London Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.ORCID 0000-0002-6948-4184
Michael J ShattockBritish Heart Foundation Centre of Research Excellence, King's College London, London, UK.
Nay AungWilliam Harvey Research Institute, John Vane Science Centre, Barts and the London Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.ORCID 0000-0001-5095-1611
Claudia P CabreraWilliam Harvey Research Institute, John Vane Science Centre, Barts and the London Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Magdi M YaqoobWilliam Harvey Research Institute, John Vane Science Centre, Barts and the London Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.
Dunja AksentijevicWilliam Harvey Research Institute, John Vane Science Centre, Barts and the London Faculty of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK.ORCID 0000-0002-8480-6727

Funding

Regulation of cardiac metabolism during LeukemiaR01HL177461 · NHLBI · CEDARS-SINAI MEDICAL CENTER · PI Anja Karlstaedt · 2025 to 2026
$1.1M
Barts Cardiovascular Biomedical Research CentreBarts CharityBarts Metabolism Network G-002145Basic Biomedical Sciences 214290/Z/18/ZBHF Centre of Research Excellence RE/18/2/34213British Heart Foundation IG/16/2/32273British Heart Foundation ref.202767/Z/16/ZCentre for Biomolecular SpectroscopyCentre of Excellence in Medical Engineering WT 203148/Z/16/ZCOSTCOST Action EU-METAHEART CA22169EPSRC Impact Acceleration Account Technology 0016113European Cooperation in Science and TechnologyEuropean Research Council COG 2018 - 819600_FIRMFondation ARC pour la Recherche sur le Cancer AIRC-MFAG 21903Fondation ARC pour la Recherche sur le Cancer ARCLEADER2022020004901King's College LondonMedical Research Council MC_UU_00014/5MIUR PRIN-2022 Prot. 202252ZLSXMRC Mouse Biochem LabNational Institute for Health and Care ResearchNHLBI NIH HHS R01 HL177461NIH HHS R01-HL177461NIHR Biomedical Research Centre at Guy'sNovo Foundation NNF21OC0068683Oxford-Bristol Myers Squibb Fellowship R39207/CN063Queen Mary University of LondonSt Thomas' NHS Foundation TrustUKRI-Biotechnology and Biological Sciences Research CouncilWellcome TrustWellcome Trust 221604/Z/20/ZWellcome Trust Senior Research Fellowship
6 · The paper itself

Abstract

aimsChronic kidney disease (CKD) is associated with uraemic cardiomyopathy characterized by early metabolic dysfunction. Elevated myocardial intracellular sodium (Naᵢ) has emerged as a driver of cardiometabolic remodelling, however, its role in CKD and therapeutic modulation remains unclear. We investigated whether dual sodium-glucose cotransporter (SGLT)1/2 inhibition with sotagliflozin (SOTA) targets Naᵢ and improves cardiac metabolism in CKD. METHODS AND

resultsCKD was induced in male Wistar rats by 5/6 nephrectomy and assessed after 4 weeks. Cardiac phenotype was evaluated using in vivo echocardiography and ex vivo Langendorff perfusion combined with 23Na and 31P NMR spectroscopy. CKD hearts exhibited preserved systolic but impaired diastolic function and a marked elevation in myocardial Naᵢ, identifying Naᵢ overload as an early feature of uraemic cardiomyopathy. Cardiac metabolomic profiling and flux modelling demonstrated widespread suppression of central carbon metabolism, redox imbalance despite preserved PCr/ATP. In silico electrophysiological simulations predicted Naᵢ-driven Ca2+ dysregulation consistent with in vivo diastolic dysfunction. Chronic SOTA treatment (3 weeks, in vivo) normalized myocardial Naᵢ and partially reversed metabolic remodelling. Acute SOTA exposure (20 min, Langendorff-perfusion) similarly reduced Naᵢ in CKD hearts but not in controls, indicating a direct, disease-selective myocardial effect. Naᵢ normalization was accompanied by improved redox state and restoration of mitochondrial metabolic flux, without changes in expression of canonical Na + -handling proteins.

conclusionMyocardial Naᵢ overload emerges as an early and potentially modifiable feature of uraemic cardiomyopathy. Dual SGLT1/2 inhibition with SOTA directly lowers Naᵢ and improves cardiac metabolic homeostasis, supporting Naᵢ as a mechanistically relevant and potentially targetable pathway in CKD-related cardiac remodelling.

Indexed as

CardiomyopathiesEnergy MetabolismGlycosidesMyocardiumMyocytes, CardiacRenal Insufficiency, ChronicSodiumSodium-Glucose Transporter 1Sodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorsUremiaVentricular Function, LeftVentricular RemodelingAnimalsDisease Models, AnimalIsolated Heart PreparationGlycosidesPyransSlc5a1 protein, ratSlc5a2 protein, ratSodiumSodium-Glucose Transporter 1Sodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorssotagliflozinCardiac metabolismCKDIntracellular sodiumSGL T1/2 inhibitionSotagliflozinUraemic cardiomyopathy

Identifiers

PMID42578286
PMCPMC13653498

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.