Protein / target

Sodium/glucose cotransporter 2

SLC5A2P31639Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
11
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Alpha-glucoside transmembrane transporter activity

Primary system

Renal system

Strongest disease association

Disorder of carbohydrate metabolism

Genetic evidence · score 0.94

Therapeutic maturity

Clinically validated target

11 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Approved Drug

Clinical development

11 approved · 6 in clinical development

30 linked trials

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function

Electrogenic Na(+)-coupled sugar symporter that actively transports D-glucose at the plasma membrane, with a Na(+) to sugar coupling ratio of 1:1 (PubMed:20980548, PubMed:28592437, PubMed:34880493, PubMed:37217492, PubMed:38057552). Transporter activity is driven by a transmembrane Na(+) electrochemical gradient set by the Na(+)/K(+) pump (PubMed:20980548, PubMed:28592437, PubMed:34880493). Unlike SLC5A1/SGLT1, requires the auxiliary protein PDZK1IP1/MAP17 for full transporter activity (PubMed:37217492). Has a primary role in D-glucose reabsorption from glomerular filtrate across the brush border of the early proximal tubules of the kidney (By similarity)

Subcellular location

Apical cell membrane
Domains and Gene Ontology detail (15)

Gene Ontology

  • Capical plasma membrane
  • Cextracellular exosome
  • Cmembrane
  • Cplasma membrane
  • Falpha-glucoside transmembrane transporter activity
  • FD-glucose transmembrane transporter activity
  • FD-glucose:sodium symporter activity
  • Flow-affinity D-glucose:sodium symporter activity
  • Fmetal ion binding
  • Palpha-glucoside transport
  • Pcarbohydrate metabolic process
  • PD-glucose import across plasma membrane

672 aa · 73 kDa · 2 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Metabolic enzyme activityGO
View supporting evidence

Metabolic enzyme activity

  • ·carbohydrate metabolic process
View underlying pathways (2)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.

PDZK1I…DPP4GLP1RADCY7INSGCGSLC6A2SLC2A2SIRENSLC5A2

10 strongest partners — larger node and heavier line mean higher confidence

Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.

Drugs targeting this protein

2

Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.

empagliflozin
Narrow target profileApprovedInhibitor

Sodium/glucose cotransporter 2 inhibitor

Appears in clinical studies involving type 2 diabetes mellitus, diabetes mellitus, type 1 diabetes mellitus, type 2 diabetes mellitus

Direct interaction with this protein · Only this protein recorded as a target

dapagliflozin
Narrow target profileApprovedInhibitor

Sodium/glucose cotransporter 2 inhibitor

Appears in clinical studies involving diabetes mellitus, type 2 diabetes mellitus, type 2 diabetes mellitus, Other metabolic disease

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.

Translational evidence

Open Targets 26

Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.

Strongest genetic associations

Human genetic evidence — the most direct causal link between this target and a disease.

Disorder of carbohydrate metabolism0.94

Genetic · overall 0.57

familial renal glucosuria0.87

Genetic · overall 0.70

carbohydrate metabolism disease0.85

Genetic · overall 0.52

Renal glucosuria0.61

Genetic · overall 0.53

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

type 2 diabetes mellitus1.00

Clinical · overall 0.64

heart failure0.99

Clinical · overall 0.63

chronic kidney disease0.98

Clinical · overall 0.63

diabetes mellitus0.96

Clinical · overall 0.62

type 1 diabetes mellitus0.94

Clinical · overall 0.61

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

systolic heart failure0.51

Clinical

Show all associations
familial renal glucosuria0.70
type 2 diabetes mellitus0.64
heart failure0.63
chronic kidney disease0.63
diabetes mellitus0.62
type 1 diabetes mellitus0.61
Disorder of carbohydrate metabolism0.57
Renal glucosuria0.53
carbohydrate metabolism disease0.52
systolic heart failure0.51

Open Targets ranks 1,448 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.

Known drugs · 17 total

DAPAGLIFLOZIN PROPANEDIOLApproval

type 2 diabetes mellitus · heart failure · type 2 diabetes mellitus

BEXAGLIFLOZINApproval

diabetes mellitus · type 2 diabetes mellitus · type 2 diabetes mellitus

TOFOGLIFLOZINApproval

type 2 diabetes mellitus · type 2 diabetes mellitus · metabolic dysfunction-associated steatohepatitis

TOFOGLIFLOZIN ANHYDROUSPhase 2

type 2 diabetes mellitus

ERTUGLIFLOZIN PIDOLATEApproval

type 2 diabetes mellitus · diabetic kidney disease · cardiovascular disorder

DAPAGLIFLOZINApproval

diabetes mellitus · type 2 diabetes mellitus · type 2 diabetes mellitus

LICOGLIFLOZINPhase 2

heart failure · type 2 diabetes mellitus · type 2 diabetes mellitus

YM-543Phase 2

type 2 diabetes mellitus · type 2 diabetes mellitus

HENAGLIFLOZINPhase 3

type 2 diabetes mellitus · heart failure · atrial fibrillation

CANAGLIFLOZIN ANHYDROUSPhase 3

type 2 diabetes mellitus

Tractability

SM · Approved DrugSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Small Molecule Binder

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.

Show remaining trials (24)

ACTIVE_NOT_RECRUITING · via dapagliflozin · NCT04451837

NOT_YET_RECRUITING · via empagliflozin · NCT03867487

RECRUITING · via empagliflozin · NCT04381936

ClinicalTrials.gov via the drug-target graph.

Forefront confidence

Synthesis

Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.

Disorder of carbohydrate metabolismWell supported
0.94
agreement 0.821.00
Genetic100%

Open Targets aggregate 0.57 · 1 independent evidence family

familial renal glucosuriaWell supported
0.90
agreement 0.781.00
Genetic79%Animal model20%Literature2%Genetic literaturedup

Open Targets aggregate 0.70 · 3 independent evidence families · 1 not counted as duplicate

carbohydrate metabolism diseaseWell supported
0.85
agreement 0.730.97
Genetic100%

Open Targets aggregate 0.52 · 1 independent evidence family

diabetes mellitusWell supported
0.80
agreement 0.670.93
Clinical71%Animal model15%Literature14%

Open Targets aggregate 0.62 · 3 independent evidence families

type 2 diabetes mellitusWell supported
0.79
agreement 0.630.94
Clinical84%Literature17%

Open Targets aggregate 0.64 · 2 independent evidence families

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.

What's happening now

27

Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.

  1. New publication2025-06-04
    Effect of dapagliflozin on metabolic dysfunction-associated steatohepatitis: multicentre, double blind, randomised, placebo controlled trial.

    BMJ (Clinical research ed.) · 2025 · 51 citations · Europe PMC · via dapagliflozin

  2. New publication2024-06-01
    Gut Microbiota-Tryptophan Metabolism-GLP-1 Axis Participates in β-Cell Regeneration Induced by Dapagliflozin.

    Diabetes · 2024 · 26 citations · Europe PMC · via dapagliflozin

  3. New publication2023-08-03
    Cardiac and Metabolic Effects of Dapagliflozin in Heart Failure With Preserved Ejection Fraction: The CAMEO-DAPA Trial.

    Circulation · 2023 · 93 citations · Europe PMC · via dapagliflozin

  4. Regulatory approval2023-03-24

    Approval: Dapagliflozin Viatris (EMA)

    ema · regulatory · ema · via dapagliflozin

  5. New publication2022-02-28
    The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial.

    Nature medicine · 2022 · 652 citations · Europe PMC · via empagliflozin

  6. Safety communication2021-12-10

    Drug Safety Update: Dapagliflozin (Forxiga): no longer authorised for treatment of type 1 diabetes mellitus

    mhra · safety · mhra · via dapagliflozin

  7. New publication2021-08-27
    Empagliflozin in Heart Failure with a Preserved Ejection Fraction.

    The New England journal of medicine · 2021 · 3,491 citations · Europe PMC · via empagliflozin

  8. New publication2021-07-01
    The effects of liraglutide and dapagliflozin on cardiac function and structure in a multi-hit mouse model of heart failure with preserved ejection fraction.

    Cardiovascular research · 2021 · 175 citations · Europe PMC · via dapagliflozin

  9. New publication2020-11-13
    Randomized Trial of Empagliflozin in Nondiabetic Patients With Heart Failure and Reduced Ejection Fraction.

    Journal of the American College of Cardiology · 2021 · 378 citations · Europe PMC · via empagliflozin

  10. New publication2020-09-24
    Dapagliflozin in Patients with Chronic Kidney Disease.

    The New England journal of medicine · 2020 · 3,783 citations · Europe PMC · via dapagliflozin

  11. New publication2020-08-28
    Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure.

    The New England journal of medicine · 2020 · 3,679 citations · Europe PMC · via empagliflozin

  12. New publication2020-04-24
    Effects of Glucagon-Like Peptide-1 Receptor Agonists, Sodium-Glucose Cotransporter-2 Inhibitors, and Their Combination on Endothelial Glycocalyx, Arterial Function, and Myocardial Work Index in Patients With Type 2 Diabetes Mellitus After 12-Month Treatment.

    Journal of the American Heart Association · 2020 · 133 citations · Europe PMC · via empagliflozin

Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.