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Protein / target

Glucagon receptor

Encoded byGCGRP47871Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
3
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Advanced Clinical

Protein at a glance

Biological role

Guanyl-nucleotide exchange factor

Primary biology

GPCR signalling

Strongest disease association

GCGR-related hyperglucagonemia

Via encoding gene GCGR · Genetic evidence · score 0.84

Therapeutic position

Established drug target

Small molecules and antibodies

Research activity

Emerging research

18 papers · latest 2025

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 overview

G protein-coupled receptor for glucagon that plays a central role in the regulation of blood glucose levels and glucose homeostasis.

View complete UniProt function annotation

G protein-coupled receptor for glucagon that plays a central role in the regulation of blood glucose levels and glucose homeostasis. Regulates the rate of hepatic glucose production by promoting glycogen hydrolysis and gluconeogenesis. Plays an important role in mediating the responses to fasting. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase (PubMed:32193322, PubMed:38346960). Promotes activation of adenylate cyclase. Besides, plays a role in signaling via a phosphatidylinositol-calcium second messenger system

Subcellular location

Cell membrane
Domains and Gene Ontology detail (16)

Gene Ontology

  • Cmembrane
  • Cplasma membrane
  • Fglucagon receptor activity
  • Fguanyl-nucleotide exchange factor activity
  • Fpeptide hormone binding
  • Padenylate cyclase-activating G protein-coupled receptor signaling pathway
  • Padenylate cyclase-modulating G protein-coupled receptor signaling pathway
  • Pcell surface receptor signaling pathway
  • Pcellular response to glucagon stimulus
  • Pcellular response to starvation
  • Pgeneration of precursor metabolites and energy
  • Pglucose homeostasis

477 aa · 54 kDa

Biological roles

Reactome v97

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

G protein-coupled signallingUniProt · GO
View supporting evidence

G protein-coupled signalling

  • ·G protein-coupled receptor for glucagon that plays a central role in the regulation of b…
  • ·adenylate cyclase-activating G protein-coupled receptor signaling pathway
  • ·adenylate cyclase-modulating G protein-coupled receptor signaling pathway
View underlying pathways (4)

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.

GCGGNASGNAQGNB1GNAI1GNG2IGHV3-…INSGIPVIPGCGR

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.

Approved medicines with mapped indications

1 medicine · 2 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Diabetes Mellitus1 medicine
Hypoglycemia1 medicine

3 medicines meet Open Targets' target-level approved-medicine definition; the 1 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

3

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

Glucagon
Narrow target profileApprovedAgonist

Glucagon receptor agonist

Indicated for Diabetes Mellitus, Hypoglycemia

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

retatrutide
Narrow target profilePhase 3Agonist

Glucagon receptor agonist

Direct interaction with this protein · 1 of 3 recorded protein targets — narrow recorded profile

Efinopegdutide
Narrow target profilePhase 2Agonist

Glucagon receptor agonist

Direct interaction with this protein · 1 of 2 recorded protein targets — narrow recorded profile

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

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene GCGR

Gene-level evidence surfaced through the gene GCGRthat encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

GCGR-related hyperglucagonemia
0.88Well supported

Genetic evidence dominant · Open Targets 0.72

Diabetes Mellitus
0.77Well supported

Clinical evidence dominant · Open Targets 0.59

Diabetes Mellitus, Type 1
0.69Moderately supported

Clinical evidence dominant · Open Targets 0.55

Diabetes Mellitus, Type 2
0.55Moderately supported

Clinical evidence dominant · Open Targets 0.42

Obesity disorder
0.51Moderately supported

Clinical evidence dominant · Open Targets 0.40

View evidence synthesis (5)
GCGR-related hyperglucagonemiaWell supported
0.88
agreement 0.761.00
Genetic79%Animal model19%Literature2%Genetic literaturedup

Open Targets aggregate 0.72 · 3 independent evidence families · 1 not counted as duplicate

Diabetes MellitusWell supported
0.77
agreement 0.650.90
Clinical72%Animal model19%Literature9%

Open Targets aggregate 0.59 · 3 independent evidence families

Diabetes Mellitus, Type 1Moderately supported
0.69
agreement 0.530.84
Clinical84%Literature16%

Open Targets aggregate 0.55 · 2 independent evidence families

Diabetes Mellitus, Type 2Moderately supported
0.55
agreement 0.400.71
Clinical80%Literature20%

Open Targets aggregate 0.42 · 2 independent evidence families

Obesity disorderModerately supported
0.51
agreement 0.360.67
Clinical89%Literature11%

Open Targets aggregate 0.40 · 2 independent evidence families

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 per-type scores above show the calculation.

Show all associations
GCGR-related hyperglucagonemia0.72
Diabetes Mellitus0.59
Diabetes Mellitus, Type 10.55
Diabetes Mellitus, Type 20.42
Obesity disorder0.40
Non-alcoholic Fatty Liver Disease0.38

Drug development

14 compounds recorded · 3 approved · 11 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 3 drugs that target this protein in Forefront's canonical graph (1 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
DASIGLUCAGON HYDROCHLORIDEApproval
ADOMEGLIVANTPhase 2
MK-3577Phase 2
GLUCAGONApproval
VOLAGIDEMABPhase 2
SAR425899Phase 2
COTADUTIDEPhase 2
DASIGLUCAGONApproval
CROTEDUMABPhase 1
RETATRUTIDEPhase 3

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesStrong

Advanced Clinical and Structure with Ligand support this modality.

AntibodiesStrong

Advanced Clinical and UniProt loc high conf support this modality.

Protein degradersEmerging

Feasibility evidence (small molecule binder) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Approved Drug support this modality.

View underlying tractability evidence (10)
SM · Advanced ClinicalSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · Advanced ClinicalAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · Small Molecule BinderOC · Approved Drug

Raw Open Targets tractability assessment buckets, by modality.

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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

NOT_YET_RECRUITING · via Glucagon · NCT07300982

NOT_YET_RECRUITING · via Glucagon · NCT06558422

ACTIVE_NOT_RECRUITING · via Glucagon · NCT03241706

ACTIVE_NOT_RECRUITING · via Glucagon · NCT02817659

COMPLETED · via Glucagon · NCT04053712

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Trial status changed2026-07-16

    A Phase 1, Investigator- and Participant-Blinded Study to Evaluate the Effect of Retatrutide on α- and β- Cell Function and Insulin Sensitivity in Adult Participants With Type 2 Diabetes Mellitus

    Status changed to Active, not recruiting · ClinicalTrials.gov · via retatrutide

  2. Product recall2026-06-23

    Recall (Not Yet Classified): GLUCAGON

    fda · safety · fda · via Glucagon

  3. Product recall2026-06-23

    Recall (Class II): GLUCAGON

    fda · safety · fda · via Glucagon

  4. New publication2026-04-01
    GLP-1 Receptor Agonists.

    The New England journal of medicine · 2026 · Europe PMC · via Glucagon

  5. New publication2024-09-01
    GLP-1, GIP, and Glucagon Agonists for Obesity Treatment: A Hunger Perspective.

    Endocrinology · 2024 · 5 citations · Europe PMC · via Glucagon

  6. New publication2024-04-27
    Glucagon resistance and metabolic-associated steatotic liver disease: a review of the evidence.

    The Journal of endocrinology · 2024 · 12 citations · Europe PMC · via Glucagon

  7. New publication2024-04-25
    Neuronal glucose sensing mechanisms and circuits in the control of insulin and glucagon secretion.

    Physiological reviews · 2024 · 15 citations · Europe PMC · via Glucagon

  8. New publication2024-03-13
    Incretin and glucagon receptor polypharmacology in chronic kidney disease.

    American journal of physiology. Endocrinology and metabolism · 2024 · 9 citations · Europe PMC · via Glucagon

  9. New publication2023-12-14
    Dose-response effects on HbA<sub>1c</sub> and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial.

    Diabetologia · 2024 · 90 citations · Europe PMC · via Glucagon

  10. New publication2023-09-09
    Results from three phase 1 trials of NNC9204-1177, a glucagon/GLP-1 receptor co-agonist: Effects on weight loss and safety in adults with overweight or obesity.

    Molecular metabolism · 2023 · 29 citations · Europe PMC · via Glucagon

  11. Regulatory approval2021-02-11

    Approval: Ogluo (EMA)

    ema · regulatory · ema · via Glucagon

  12. Regulatory approval2019-12-16

    Approval: Baqsimi (EMA)

    ema · regulatory · ema · via Glucagon

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.

Research activity

18 papers · to 2025

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Recent

Incretin and glucagon receptor polypharmacology in chronic kidney disease.

McFarlin BE · American journal of physiology. Endocrinology and metabolism · 2024

Mechanisms of action of incretin receptor based dual- and tri-agonists in pancreatic islets.

Folli F · American journal of physiology. Endocrinology and metabolism · 2023

Structural analysis of the dual agonism at GLP-1R and GCGR.

Li Y · Proceedings of the National Academy of Sciences of the United States of America · 2023

Glucagon Receptor Signaling and Glucagon Resistance.

Janah L · International journal of molecular sciences · 2019

Glucagon-like peptide 1 (GLP-1).

Müller TD · Molecular metabolism · 2019

Europe PMC papers linked directly to this protein.