Affinage

SLC5A2

Sodium/glucose cotransporter 2 · UniProt P31639

Length
672 aa
Mass
72.9 kDa
Annotated
2026-06-10
100 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC5A2 (SGLT2) is the dominant electrogenic sodium-coupled glucose cotransporter of the renal proximal tubule, where it carries out the bulk of filtered glucose reabsorption: genetic deletion in mice produces ~500-fold glucosuria with preserved pancreatic β-cell function (PMID:21357472), and single-cell profiling localizes its expression exclusively to the proximal tubular cell cluster (PMID:36637914). Loss-of-function mutations across the SLC5A2 coding sequence cause familial renal glucosuria, with the K321R substitution in the eighth transmembrane domain marking a region critical for transport and homozygous lesions producing massive glucosuria accompanied by renal sodium wasting and renin-angiotensin-aldosterone activation, confirming that glucose reabsorption is sodium-coupled in vivo (PMID:15610225, PMID:16518345). Beyond glucose, SGLT2 transports aminoglycosides into proximal tubule cells, accounting for their cellular uptake and cytotoxicity (PMID:25268124), and it coordinates a broad apical uptake transport network whose components are downregulated upon SGLT2 inhibition (PMID:38152989). Pharmacological SGLT2 blockade enhances fractional urate excretion through a URAT1-dependent luminal-glucose mechanism (PMID:30427222) and via activation of an ERRα–OAT1 axis (PMID:39168099), and suppresses mTORC1 signaling across nephron segments (PMID:36637914). Outside the kidney, SGLT2 is functionally expressed in pancreatic α-cells where its inhibition stimulates glucose-dependent glucagon secretion (PMID:31896553), in cardiomyocytes where high glucose upregulates it and drives TET2-mediated promoter demethylation of NF-κB and SOD2 (PMID:36732760, PMID:36096423), in cytokine-stimulated endothelial cells where it propagates dysfunction and thrombotic signaling (PMID:37797691), and in breast and lung cancer cells where it supports proliferation (PMID:31776304, PMID:30365049).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2005 Medium

    Establishing which protein regions are essential for human glucose transport, a homozygous missense mutation pinpointed the eighth transmembrane domain as critical for SGLT2 function.

    Evidence SLC5A2 coding sequencing and haplotype analysis in consanguineous familial renal glucosuria families

    PMID:15610225

    Open questions at the time
    • No in vitro reconstitution of the K321R transport defect
    • Does not quantify residual transport activity
  2. 2006 Medium

    By characterizing multiple loss-of-function alleles together with their physiological phenotypes, this work demonstrated that SGLT2-mediated glucose reabsorption is coupled to sodium reabsorption in vivo.

    Evidence SLC5A2 sequencing plus plasma renin/aldosterone phenotyping in familial renal glucosuria families

    PMID:16518345

    Open questions at the time
    • No in vitro transport reconstitution of the mutant alleles
    • Sodium coupling inferred from RAAS activation rather than direct flux measurement
  3. 2011 High

    Whether SGLT2 is the principal renal glucose-reabsorption pathway and whether its loss is metabolically tolerated was resolved by genetic deletion, which caused massive glucosuria yet preserved β-cell function.

    Evidence SGLT2 knockout mouse with metabolic cages, glucose tolerance tests, clamps, and islet perifusion

    PMID:21357472

    Open questions at the time
    • Does not address extrarenal SGLT2 functions
    • Mechanism of β-cell mass increase not defined
  4. 2014 High

    Beyond glucose, SGLT2 was shown to be a route for proximal tubule uptake of aminoglycosides, explaining a cellular basis for their nephrotoxicity.

    Evidence Competitive uptake assays, phlorizin inhibition, transfection gain-of-function, siRNA knockdown, and Sglt2-null mice

    PMID:25268124

    Open questions at the time
    • Transport stoichiometry for aminoglycosides not determined
    • Generalizability to other aminoglycosides beyond gentamicin not tested
  5. 2018 High

    The mechanism by which SGLT2 inhibition affects urate handling was mapped to luminal glucose delivery acting through URAT1 rather than tubular GLUT9.

    Evidence Canagliflozin treatment plus Sglt2-, Sglt1-, Urat1-, and tubule-specific Glut9-knockout mice with renal clearance studies

    PMID:30427222

    Open questions at the time
    • Molecular link between luminal glucose and URAT1 activity not resolved
    • Human relevance not directly tested
  6. 2019 Medium

    Extending SGLT2 function beyond kidney, expression and inhibitor-sensitive proliferation were demonstrated in breast cancer cells, implicating SGLT2 in supporting tumor cell growth.

    Evidence RT-PCR, IHC, BrdU assay, siRNA knockdown rescue, and patch-clamp in MCF-7 cells

    PMID:31776304

    Open questions at the time
    • Single cell line, single lab
    • In vivo tumor relevance not established
  7. 2020 High

    The basis for SGLT2-inhibitor effects on glucagon was established by localizing SGLT2 to pancreatic α-cells and linking expression heterogeneity to glucagon-secretion responses.

    Evidence RNA-seq of 207 donors, validated antibody immunofluorescence, and glucagon secretion assays from human islets

    PMID:31896553

    Open questions at the time
    • Transport mechanism within α-cells not defined
    • Signaling pathway from SGLT2 to glucagon release not resolved
  8. 2022 Medium

    Whether SGLT2 is expressed in human heart was addressed by detecting it in cardiomyocytes with upregulation in diabetic failing hearts and by high glucose.

    Evidence IHC, immunofluorescence, Western blot, and RT-qPCR on human hearts and AC16 cardiomyocytes

    PMID:36096423

    Open questions at the time
    • No functional glucose transport assay in cardiomyocytes
    • Single lab
  9. 2023 Medium

    Connecting renal SGLT2 to a growth/stress signaling node, inhibition was shown to suppress mTORC1 signaling across nephron segments.

    Evidence scRNA-seq of human kidney biopsies plus phospho-S6 immunostaining in SGLT2i-treated versus untreated T2D patients

    PMID:36637914

    Open questions at the time
    • Direct mechanistic link from transport activity to mTORC1 not reconstituted
    • Distal-tubule effect (lacking SGLT2) implies indirect mechanism
  10. 2023 Medium

    A cardiac epigenetic role was defined by showing SGLT2 is required for high-glucose-induced TET2-mediated demethylation of NF-κB and SOD2 promoters.

    Evidence AC16 high-glucose model with siRNA silencing, pyrosequencing methylation, and ChIP-qPCR for TET2

    PMID:36732760

    Open questions at the time
    • Mechanism linking SGLT2 transport to TET2 recruitment unknown
    • Single cell line
  11. 2023 Medium

    An endothelial inflammatory circuit was established in which proinflammatory cytokines drive redox-sensitive SGLT2 upregulation that propagates endothelial dysfunction and thrombotic signaling.

    Evidence Porcine coronary endothelial cells with COVID-19 plasma, cytokine neutralization, empagliflozin, and platelet/thrombin assays

    PMID:37797691

    Open questions at the time
    • Direct transport function in endothelium not measured
    • Ex vivo/in vitro model only
  12. 2023 Medium

    A podocyte role was demonstrated by showing SGLT2 mediates mTORC1 activity and that its inhibition attenuates podocyte injury in lupus nephritis.

    Evidence CRISPR/Cas9 SGLT2-knockout podocyte line plus empagliflozin in MRL/lpr mice with mTORC1 assays

    PMID:37487609

    Open questions at the time
    • Single lab
    • Coupling between glucose transport and mTORC1 in podocytes not mechanistically defined
  13. 2023 Medium

    Multi-omic profiling revealed that SGLT2 inhibition broadly downregulates the proximal-tubule apical transport machinery and identified an SGLT2 interactome consistent with coordinated transport regulation.

    Evidence Proteomics, phosphoproteomics, metabolomics, and SGLT2 interactome studies in mouse and human tissue

    PMID:38152989

    Open questions at the time
    • Individual interactome partners not orthogonally validated
    • Direct versus indirect transporter downregulation not distinguished
  14. 2024 Medium

    A transcriptional target was identified by showing dapagliflozin activates an ERRα–OAT1 axis to enhance urate excretion and reduce fibrosis.

    Evidence Transcriptomics, ERRα knockin mice, ERRα-overexpressing HK-2 cells, and dual-luciferase reporter assays

    PMID:39168099

    Open questions at the time
    • Whether ERRα effect is independent of glucose transport unclear
    • Single lab
  15. 2024 Medium

    Lung cancer dependency was established by showing miR-296-5p represses SGLT2 and that SGLT2 is functionally required for proliferation and cell-cycle progression.

    Evidence RT-qPCR/Western blot in lung cancer samples, miR-296-5p overexpression, siRNA knockdown, and proliferation/cell-cycle assays

    PMID:30365049

    Open questions at the time
    • In vivo tumor relevance not tested
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How SGLT2 transport activity is mechanistically coupled to its extrarenal signaling effects (mTORC1 suppression, TET2-dependent demethylation, ERRα activation) remains unresolved.
  • No structural model linking transport to signaling outputs
  • Direct versus inhibitor-pleiotropic mechanisms not separated
  • Interactome partners not individually validated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 3
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-382551 Transport of small molecules 3
Partners
ESRRAOAT1SLC2A9URAT1

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 SGLT2 (SLC5A2) mediates cellular uptake of aminoglycosides (gentamicin) in kidney proximal tubule cells. D-glucose competitively decreased gentamicin uptake, phlorizin (SGLT2 antagonist) inhibited uptake in a dose- and time-dependent manner, SGLT2 transfection of distal tubule cells enhanced gentamicin uptake, siRNA knockdown of SGLT2 reduced gentamicin-induced cytotoxicity, and phlorizin failed to inhibit uptake in Sglt2-null mice. Competitive uptake assay with fluorescent glucose analog, phlorizin inhibition, SGLT2 transfection of KDT3 cells, siRNA knockdown, Sglt2 knockout mice with in vivo GTTR uptake measurement PloS one High 25268124
2011 SGLT2 deletion in mice causes a ~500-fold increase in glucosuria, demonstrating that SGLT2 is the dominant pathway for renal glucose reabsorption in the proximal tubule. Knockout mice were protected from high-fat diet-induced hyperglycemia and had preserved pancreatic β-cell function and increased β-cell mass. SGLT2 knockout mouse model; metabolic cages, glucose tolerance tests, euglycemic and hyperglycemic clamps, isolated islet and perifusion studies Diabetes High 21357472
2005 A homozygous missense mutation K321R in the eighth transmembrane domain of SGLT2 (SLC5A2) causes severe familial renal glucosuria, establishing that this domain is critical for normal glucose transport function. DNA sequencing of entire SLC5A2 coding region, PCR-RFLP confirmation, haplotype analysis in consanguineous families with familial renal glucosuria Kidney international Medium 15610225
2006 Multiple novel loss-of-function mutations in SLC5A2 (including IVS12+1G>A, p.A102V homozygous, compound heterozygous p.R132H/p.A219T, and p.Q167fsX186 frameshift) cause familial renal glucosuria, and massive glucosuria from homozygous p.A102V is associated with renal sodium wasting and activation of the renin-angiotensin-aldosterone system, indicating that SGLT2-mediated glucose reabsorption is coupled to sodium reabsorption in vivo. SLC5A2 coding region sequencing, PCR amplification, phenotypic characterization including plasma renin and aldosterone measurement Kidney international Medium 16518345
2018 SGLT2 inhibition increases fractional renal urate excretion through a mechanism requiring URAT1 but not tubular GLUT9; increased luminal glucose delivery (as shown by additive effects of combined Sglt2/Sglt1 genetic ablation) contributes to the uricosuric effect. Pharmacological and genetic SGLT2 inhibition also upregulated renal Glut9 mRNA. Canagliflozin treatment in non-diabetic mice; gene-targeted Sglt2-KO, Sglt1-KO, Urat1-KO, and tubule-specific Glut9-KO mice; renal clearance studies with FITC-sinistrin for GFR; urate measurement in plasma and urine American journal of physiology. Renal physiology High 30427222
2020 SGLT2 is expressed in human pancreatic α-cells (but not β-cells or δ-cells), and inter-individual heterogeneity in SGLT2 protein expression correlates with variability in dapagliflozin-induced glucagon secretion; SGLT2 inhibition directly stimulates glucagon secretion from human islets in a glucose-dependent manner. RNA sequencing of 207 donors; rigorously validated anti-SGLT2 antibody; Western blot and immunofluorescence on islets from 10–12 donors; quantitative colocalization analysis of 665 human islets; glucagon secretion assays from 31 donors with dapagliflozin Diabetes High 31896553
2019 SGLT2 is functionally expressed in human breast cancer MCF-7 cells and mediates glucose-induced whole-cell sodium current; ipragliflozin (SGLT2 inhibitor) suppressed MCF-7 proliferation in a dose-dependent manner, and this effect was completely abolished by SGLT2 knockdown, indicating on-target SGLT2-mediated action. SGLT2 inhibition also caused membrane hyperpolarization and mitochondrial membrane potential changes. RT-PCR, immunohistochemistry, BrdU proliferation assay, siRNA knockdown, patch-clamp electrophysiology (membrane potential and whole-cell current) Endocrine journal Medium 31776304
2023 SGLT2 inhibition with empagliflozin in human cardiomyocytes exposed to high glucose prevents TET2-mediated DNA demethylation at NF-κB and SOD2 promoters, reducing their aberrant gene expression. Transient SGLT2 gene silencing alone recapitulated the prevention of demethylation, establishing SGLT2 as required for high-glucose-induced epigenetic changes in cardiomyocytes. AC16 cardiomyocyte high-glucose model; pyrosequencing-based methylation analysis; siRNA SGLT2 silencing; chromatin immunoprecipitation-qPCR for TET2 occupancy; RT-qPCR and Western blot Cardiovascular diabetology Medium 36732760
2022 SGLT2 protein is expressed in human cardiomyocytes; expression is increased in diabetic versus non-diabetic failing hearts and is upregulated by high glucose in cultured AC16 human cardiomyocytes, as confirmed by immunofluorescence colocalization, Western blot, and RT-PCR. Immunohistochemistry, immunofluorescence, Western blot, RT-qPCR on explanted human hearts and endomyocardial biopsies; high-glucose treatment of AC16 cells Pharmacological research Medium 36096423
2023 SGLT2 expression is increased and colocalizes with decreased synaptopodin in podocytes of lupus nephritis patients and MRL/lpr mice; CRISPR/Cas9-generated SGLT2 knockout podocyte cells show that SGLT2 mediates mTORC1 activity, and empagliflozin attenuates podocyte injury by reducing mTORC1 activity and enhancing autophagy. CRISPR/Cas9 SGLT2 knockout podocyte cell line; empagliflozin treatment of MRL/lpr mice; immunofluorescence colocalization; mTORC1 activity assays Annals of the rheumatic diseases Medium 37487609
2023 SGLT2 inhibitor treatment broadly downregulates the apical uptake transport machinery (including sodium, glucose, urate, purine bases, and amino acid transporters) in the proximal tubule; mouse and human SGLT2 interactome studies revealed binding partners consistent with this coordinated transport regulation. Proteomics, phosphoproteomics, metabolomics of kidneys/heart/liver/adipose in nondiabetic and diabetic mice after 1 week SGLT2i; SGLT2 interactome studies in mouse and human tissue Circulation Medium 38152989
2021 SGLT2 is expressed at mRNA and protein levels in the proximal tubule; single-cell RNA sequencing of human kidney biopsies confirms SGLT2 expression exclusively in the proximal tubular cell cluster, and SGLT2 inhibitor treatment suppresses mTORC1 signaling across nephron segments, with decreased phospho-S6 protein in both proximal and distal tubules confirmed by immunostaining. Single-cell RNA sequencing of research kidney biopsies from youth-onset T2D patients and healthy controls; phospho-S6 immunostaining; comparison of SGLT2i-treated vs. untreated T2D patients The Journal of clinical investigation Medium 36637914
2023 COVID-19 proinflammatory cytokines (IL-1β, IL-6, TNF-α) induce redox-sensitive SGLT2 upregulation in endothelial cells, which in turn drives endothelial dysfunction, senescence, NF-κB activation, platelet adhesion/aggregation, and thrombin generation; neutralizing antibodies against these cytokines and empagliflozin both blocked this pathway. Porcine coronary artery endothelial cells incubated with COVID-19 patient plasma; Western blot, immunofluorescence, RT-qPCR; dihydroethidium for oxidative stress; neutralizing antibody blockade; empagliflozin treatment; platelet adhesion/aggregation and thrombin generation assays Journal of thrombosis and haemostasis Medium 37797691
2019 A novel compound heterozygous mutation (p.W172R; p.P514S) in SLC5A2 is associated with familial renal glucosuria, extending the catalog of loss-of-function mutations that disrupt SGLT2-mediated glucose reabsorption. SLC5A2 gene sequencing; in silico functional prediction tools; literature review of 86 SLC5A2 mutations Molecular medicine reports Low 30942416
2024 SGLT2 inhibitor dapagliflozin targets estrogen-related receptor α (ERRα), activating the ERRα–OAT1 axis to enhance uric acid excretion and reduce tubulointerstitial fibrosis in hyperuricemic nephropathy; dual-luciferase reporter assays confirmed transcription factor binding, and ERRα knockin mice showed UA resistance. Transcriptomic analysis of patients and HN mice; HK-2 cell UA stimulation; ERRα knockin mice; ERRα-overexpressed HK-2 cells; dual-luciferase reporter assay; ERRα inhibition; dapagliflozin treatment in vivo and in vitro Cell reports. Medicine Medium 39168099
2024 MicroRNA-296-5p directly targets and downregulates SGLT2 in lung cancer cells; siRNA knockdown of SGLT2 inhibited cell proliferation and impeded cell cycle progression, establishing SGLT2 as functionally required for lung cancer cell growth. RT-qPCR and Western blot in human lung cancer samples and cell lines; miR-296-5p overexpression; siRNA SGLT2 knockdown; proliferation and cell cycle assays International journal of oncology Medium 30365049

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2019 SGLT2 inhibition with empagliflozin attenuates myocardial oxidative stress and fibrosis in diabetic mice heart. Cardiovascular diabetology 482 30710997
2021 SGLT2 inhibitors and GLP-1 receptor agonists: established and emerging indications. Lancet (London, England) 439 34216571
2012 SGLT2 inhibition in diabetes mellitus: rationale and clinical prospects. Nature reviews. Endocrinology 363 22310849
2022 Critical Reanalysis of the Mechanisms Underlying the Cardiorenal Benefits of SGLT2 Inhibitors and Reaffirmation of the Nutrient Deprivation Signaling/Autophagy Hypothesis. Circulation 336 36315602
2015 Probing SGLT2 as a therapeutic target for diabetes: basic physiology and consequences. Diabetes & vascular disease research 312 25616707
2020 SGLT2 Inhibition Mediates Protection from Diabetic Kidney Disease by Promoting Ketone Body-Induced mTORC1 Inhibition. Cell metabolism 307 32726607
2018 Development of SGLT1 and SGLT2 inhibitors. Diabetologia 277 30132033
2014 The mechanisms and therapeutic potential of SGLT2 inhibitors in diabetes mellitus. Annual review of medicine 263 25341005
2021 Neuroprotective Effect of SGLT2 Inhibitors. Molecules (Basel, Switzerland) 233 34885795
2019 SGLT2 Inhibitors: A Review of Their Antidiabetic and Cardioprotective Effects. International journal of environmental research and public health 199 31426529
2011 SGLT2 deletion improves glucose homeostasis and preserves pancreatic beta-cell function. Diabetes 185 21357472
2022 Prescribing SGLT2 Inhibitors in Patients With CKD: Expanding Indications and Practical Considerations. Kidney international reports 166 35812300
2017 Combination therapy with GLP-1 receptor agonist and SGLT2 inhibitor. Diabetes, obesity & metabolism 153 28432726
2016 Dapagliflozin, SGLT2 Inhibitor, Attenuates Renal Ischemia-Reperfusion Injury. PloS one 147 27391020
2021 Cardioprotective mechanism of SGLT2 inhibitor against myocardial infarction is through reduction of autosis. Protein & cell 143 33417139
2018 SGLT2 inhibition and renal urate excretion: role of luminal glucose, GLUT9, and URAT1. American journal of physiology. Renal physiology 140 30427222
2011 Glucose dynamics and mechanistic implications of SGLT2 inhibitors in animals and humans. Kidney international. Supplement 139 21358698
2023 Metabolic Communication by SGLT2 Inhibition. Circulation 120 38152989
2024 SGLT2 inhibitors: from glucose-lowering to cardiovascular benefits. Cardiovascular research 115 38456601
2024 SGLT2 inhibition eliminates senescent cells and alleviates pathological aging. Nature aging 100 38816549
2023 SGLT2 inhibitors mitigate kidney tubular metabolic and mTORC1 perturbations in youth-onset type 2 diabetes. The Journal of clinical investigation 98 36637914
2022 Sodium-glucose cotransporter-2 (SGLT2) expression in diabetic and non-diabetic failing human cardiomyocytes. Pharmacological research 92 36096423
2023 SGLT2 inhibitors alleviated podocyte damage in lupus nephritis by decreasing inflammation and enhancing autophagy. Annals of the rheumatic diseases 89 37487609
2018 Risks Associated with SGLT2 Inhibitors: An Overview. Current drug safety 89 29485006
2023 Dapagliflozin protects against chronic heart failure in mice by inhibiting macrophage-mediated inflammation, independent of SGLT2. Cell reports. Medicine 82 38118414
2021 Chronic Kidney Disease and SGLT2 Inhibitors: A Review of the Evolving Treatment Landscape. Advances in therapy 82 34846711
2020 SGLT2-inhibitors; more than just glycosuria and diuresis. Heart failure reviews 80 33274396
2022 SGLT2 Inhibition, Choline Metabolites, and Cardiometabolic Diseases: A Mediation Mendelian Randomization Study. Diabetes care 75 36161993
2020 Diabetic Agents, From Metformin to SGLT2 Inhibitors and GLP1 Receptor Agonists: JACC Focus Seminar. Journal of the American College of Cardiology 75 32327107
2005 A novel missense mutation in SLC5A2 encoding SGLT2 underlies autosomal-recessive renal glucosuria and aminoaciduria. Kidney international 75 15610225
2019 SGLT2 inhibitor ipragliflozin attenuates breast cancer cell proliferation. Endocrine journal 72 31776304
2006 Familial renal glucosuria: SLC5A2 mutation analysis and evidence of salt-wasting. Kidney international 71 16518345
2023 Insights into SGLT2 inhibitor treatment of diabetic cardiomyopathy: focus on the mechanisms. Cardiovascular diabetology 70 37055837
2023 SGLT2 Inhibitors as Potential Anticancer Agents. Biomedicines 70 37509506
2022 SGLT2 inhibitor counteracts NLRP3 inflammasome via tubular metabolite itaconate in fibrosis kidney. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 66 34918381
2023 Sodium-glucose cotransporter 2 (SGLT2) inhibitors and non-small cell lung cancer survival. British journal of cancer 65 36765176
2012 Effects of SGLT2 inhibitors on cardiovascular outcomes. Diabetes & vascular disease research 61 22381403
2024 Hyperuricemia and Gout Reduction by SGLT2 Inhibitors in Diabetes and Heart Failure: JACC Review Topic of the Week. Journal of the American College of Cardiology 60 38199714
2022 Potential Interactions When Prescribing SGLT2 Inhibitors and Intravenous Iron in Combination in Heart Failure. JACC. Heart failure 60 36396554
2022 Renal and Vascular Effects of Combined SGLT2 and Angiotensin-Converting Enzyme Inhibition. Circulation 55 35862082
2023 Unlocking the Full Potential of SGLT2 Inhibitors: Expanding Applications beyond Glycemic Control. International journal of molecular sciences 54 37047011
2023 SGLT2 Inhibitors vs. GLP-1 Agonists to Treat the Heart, the Kidneys and the Brain. Journal of cardiovascular development and disease 53 37623335
2023 SGLT2 inhibition, circulating metabolites, and atrial fibrillation: a Mendelian randomization study. Cardiovascular diabetology 53 37848934
2015 SGLT2 inhibition: efficacy and safety in type 2 diabetes treatment. Expert opinion on drug safety 53 26513131
2023 Finerenone Added to RAS/SGLT2 Blockade for CKD in Alport Syndrome. Results of a Randomized Controlled Trial with Col4a3-/- Mice. Journal of the American Society of Nephrology : JASN 51 37428955
2024 SGLT2 inhibitor promotes ketogenesis to improve MASH by suppressing CD8+ T cell activation. Cell metabolism 48 39243758
2023 SGLT2 inhibitor ameliorates endothelial dysfunction associated with the common ALDH2 alcohol flushing variant. Science translational medicine 48 36696485
2025 Anti-Inflammatory Effects of SGLT2 Inhibitors: Focus on Macrophages. International journal of molecular sciences 47 40004134
2024 Effects of the Nonsteroidal MRA Finerenone With and Without Concomitant SGLT2 Inhibitor Use in Heart Failure. Circulation 45 39340828
2024 SGLT2 inhibitors ameliorate NAFLD in mice via downregulating PFKFB3, suppressing glycolysis and modulating macrophage polarization. Acta pharmacologica Sinica 44 39294445
2022 Antioxidant Roles of SGLT2 Inhibitors in the Kidney. Biomolecules 43 35053290
2020 Interindividual Heterogeneity of SGLT2 Expression and Function in Human Pancreatic Islets. Diabetes 43 31896553
2014 Sodium-glucose transporter-2 (SGLT2; SLC5A2) enhances cellular uptake of aminoglycosides. PloS one 43 25268124
2015 SGLT2 inhibitors. Biochemical pharmacology 41 26362302
2024 Acute antiarrhythmic effects of SGLT2 inhibitors-dapagliflozin lowers the excitability of atrial cardiomyocytes. Basic research in cardiology 39 38170280
2024 The SGLT2 inhibitor dapagliflozin ameliorates renal fibrosis in hyperuricemic nephropathy. Cell reports. Medicine 39 39168099
2023 Targeting high glucose-induced epigenetic modifications at cardiac level: the role of SGLT2 and SGLT2 inhibitors. Cardiovascular diabetology 39 36732760
2016 The renal effects of SGLT2 inhibitors and a mini-review of the literature. Therapeutic advances in endocrinology and metabolism 39 28203358
2024 Targeting inflammatory signaling pathways with SGLT2 inhibitors: Insights into cardiovascular health and cardiac cell improvement. Current problems in cardiology 38 38492622
2024 Sodium-glucose co-transporter protein 2 (SGLT2) inhibitors for people with chronic kidney disease and diabetes. The Cochrane database of systematic reviews 38 38770818
2017 ACE and SGLT2 inhibitors: the future for non-diabetic and diabetic proteinuric renal disease. Current opinion in pharmacology 38 28482281
2024 Empagliflozin prevents heart failure through inhibition of the NHE1-NO pathway, independent of SGLT2. Basic research in cardiology 37 39046464
2023 SGLT2 inhibition ameliorates nano plastics-induced premature endothelial senescence and dysfunction. Scientific reports 36 37069192
2021 The Role of SGLT2 Inhibitors in Vascular Aging. Aging and disease 36 34341711
2017 Influence of common polymorphisms in the SLC5A2 gene on metabolic traits in subjects at increased risk of diabetes and on response to empagliflozin treatment in patients with diabetes. Pharmacogenetics and genomics 35 28134748
2023 The effect of SGLT2 inhibitors on the endothelium and the microcirculation: from bench to bedside and beyond. European heart journal. Cardiovascular pharmacotherapy 34 37500266
2018 SGLT2 inhibition and glucagon secretion in humans. Diabetes & metabolism 34 30017776
2016 Positioning SGLT2 Inhibitors/Incretin-Based Therapies in the Treatment Algorithm. Diabetes care 34 27440828
2022 Effects and mechanisms of SGLT2 inhibitors on the NLRP3 inflammasome, with a focus on atherosclerosis. Frontiers in endocrinology 33 36589841
2023 SGLT-2 Inhibitors and the Inflammasome: What's Next in the 21st Century? Nutrients 32 37242177
2024 SGLT2 inhibitors and AMPK: The road to cellular housekeeping? Cell biochemistry and function 30 38269506
2018 A comparative safety review between GLP-1 receptor agonists and SGLT2 inhibitors for diabetes treatment. Expert opinion on drug safety 30 29334278
2024 Role and molecular mechanisms of SGLT2 inhibitors in pathological cardiac remodeling (Review). Molecular medicine reports 27 38488029
2024 SGLT2 inhibition and three urological cancers: Up-to-date results. Diabetes/metabolism research and reviews 26 38523292
2021 Peritoneal Expression of SGLT-2, GLUT1, and GLUT3 in Peritoneal Dialysis Patients. Kidney & blood pressure research 26 34781282
2024 SGLT2 inhibitor promotes mitochondrial dysfunction and ER-phagy in colorectal cancer cells. Cellular & molecular biology letters 25 38811901
2023 COVID-19 promotes endothelial dysfunction and thrombogenicity: role of proinflammatory cytokines/SGLT2 prooxidant pathway. Journal of thrombosis and haemostasis : JTH 25 37797691
2018 MicroRNA-296, a suppressor non-coding RNA, downregulates SGLT2 expression in lung cancer. International journal of oncology 20 30365049
2015 The Role of the Kidney and SGLT2 Inhibitors in Type 2 Diabetes. Canadian journal of diabetes 20 26654860
2024 SGLT2 inhibitor use in the management of feline diabetes mellitus. Journal of veterinary pharmacology and therapeutics 19 38954371
2022 Targeting Features of the Metabolic Syndrome Through Sympatholytic Effects of SGLT2 Inhibition. Current hypertension reports 19 35235172
2019 A novel compound heterozygous mutation in SLC5A2 contributes to familial renal glucosuria in a Chinese family, and a review of the relevant literature. Molecular medicine reports 19 30942416
2025 SGLT2 Inhibitors and GLP-1 Receptor Agonists in Cardiovascular-Kidney-Metabolic Syndrome. Biomedicines 18 40868177
2016 Effects of Incretin-Based Therapies and SGLT2 Inhibitors on Skeletal Health. Current osteoporosis reports 18 27709509
2025 SGLT2 inhibitors as a novel senotherapeutic approach. npj aging 17 40348751
2024 SGLT2 inhibitor downregulates ANGPTL4 to mitigate pathological aging of cardiomyocytes induced by type 2 diabetes. Cardiovascular diabetology 17 39633372
2023 The SGLT2 Inhibitor Canagliflozin Reduces Atherosclerosis by Enhancing Macrophage Autophagy. Journal of cardiovascular translational research 17 37126209
2024 SGLT2 inhibition to target kidney aging. Clinical kidney journal 16 38803397
2023 The SGLT2 inhibitor dapagliflozin improves kidney function in glycogen storage disease XI. Science translational medicine 16 37910600
2025 SGLT2 inhibitor empagliflozin ameliorates tubulointerstitial fibrosis in DKD by downregulating renal tubular PKM2. Cellular and molecular life sciences : CMLS 15 40237854
2025 A retrospective analysis of combination therapy with GLP-1 receptor agonists and SGLT2 inhibitors versus SGLT2 inhibitor monotherapy in patients with MASLD. Nature communications 15 40796776
2023 SGLT2 is upregulated to acquire cisplatin resistance and SGLT2 inhibition reduces cisplatin resistance in hepatoblastoma. Journal of hepato-biliary-pancreatic sciences 15 37927142
2025 SGLT2 inhibitors in CKD: are they really effective in all patients? Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 14 40053507
2024 Role of SGLT2 Inhibitors, DPP-4 Inhibitors, and Metformin in Pancreatic Cancer Prevention. Cancers 14 38611003
2024 SGLT2 inhibitors attenuate endothelial to mesenchymal transition and cardiac fibroblast activation. Scientific reports 14 39013942
2024 Multifaceted Impact of SGLT2 Inhibitors in Heart Failure Patients: Exploring Diverse Mechanisms of Action. Biomedicines 14 39457625
2023 The SGLT2 inhibitor empagliflozin attenuates atherosclerosis progression by inducing autophagy. Journal of physiology and biochemistry 14 37792168
2023 SGLT2 inhibitor dapagliflozin protects the kidney in a murine model of Balkan nephropathy. American journal of physiology. Renal physiology 14 38031729
2024 Mineralocorticoid Receptor Antagonist Combined with SGLT2 Inhibitor versus SGLT2 Inhibitor Alone in Chronic Kidney Disease: A Meta-Analysis of Randomized Trials. American journal of nephrology 13 39510041
2022 SGLT2 inhibitors in non-diabetic kidney disease. Advances in clinical and experimental medicine : official organ Wroclaw Medical University 13 35077036

Missed literature

Know a paper Affinage missed for SLC5A2? Flag it for the maintainers and the community.

No submissions yet.