Protein / target

Glucagon receptor

GCGRP47871Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
3
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Advanced Clinical

Protein at a glance

Biological role

Guanyl-nucleotide exchange factor activity

Primary system

Endocrine & metabolic

Strongest disease association

GCGR-related hyperglucagonemia

Genetic evidence · score 0.84

Therapeutic maturity

Clinically validated target

3 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Advanced Clinical

Clinical development

3 approved · 11 in clinical development

30 linked trials

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

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 · GOTranscriptional regulationGO
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

Transcriptional regulation

  • ·positive regulation of gene expression
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.

Drugs targeting this protein

1

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.

Glucagon
Narrow target profileApprovedAgonist

Glucagon receptor agonist

Appears in clinical studies involving Hypoglycemia, diabetes mellitus, type 1 diabetes mellitus, Hyperglycemia

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.

GCGR-related hyperglucagonemia0.84

Genetic · overall 0.72

Highest-confidence therapeutic associations

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

Hypoglycemia0.96

Clinical · overall 0.59

diabetes mellitus0.93

Clinical · overall 0.59

type 1 diabetes mellitus0.86

Clinical · overall 0.55

type 2 diabetes mellitus0.65

Clinical · overall 0.42

obesity disorder0.64

Clinical · overall 0.40

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

Obesity0.40

Clinical

metabolic dysfunction-associated steatohepatitis0.38

Clinical

Overweight0.37

Clinical

congenital isolated hyperinsulinism0.30

Clinical

Show all associations
GCGR-related hyperglucagonemia0.72
Hypoglycemia0.59
diabetes mellitus0.59
type 1 diabetes mellitus0.55
type 2 diabetes mellitus0.42
obesity disorder0.40
Obesity0.40
metabolic dysfunction-associated steatohepatitis0.38
Overweight0.37
congenital isolated hyperinsulinism0.30

Open Targets ranks 455 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 · 14 total

DASIGLUCAGON HYDROCHLORIDEApproval

diabetes mellitus · Hypoglycemia · type 1 diabetes mellitus

ADOMEGLIVANTPhase 2

type 2 diabetes mellitus · type 2 diabetes mellitus · type 1 diabetes mellitus

MK-3577Phase 2

type 2 diabetes mellitus

GLUCAGONApproval

Hypoglycemia · diabetes mellitus · type 1 diabetes mellitus

VOLAGIDEMABPhase 2

type 1 diabetes mellitus · type 1 diabetes mellitus · type 1 diabetes mellitus

SAR425899Phase 2

type 2 diabetes mellitus · metabolic dysfunction-associated steatotic liver disease · metabolic dysfunction-associated steatohepatitis

COTADUTIDEPhase 2

type 2 diabetes mellitus · type 2 diabetes mellitus · chronic kidney disease

DASIGLUCAGONApproval

Hypoglycemia · type 1 diabetes mellitus · congenital isolated hyperinsulinism

CROTEDUMABPhase 1

type 2 diabetes mellitus · type 2 diabetes mellitus

RETATRUTIDEPhase 3

Obesity · cardiovascular disorder · obesity disorder

Tractability

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

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)

TERMINATED · via Glucagon · NCT05960565

COMPLETED · via Glucagon · NCT04300049

COMPLETED · via Glucagon · NCT03526445

COMPLETED · via Glucagon · NCT04347252

ClinicalTrials.gov via the drug-target graph.

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.

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.

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

HypoglycemiaModerately supported
0.73
agreement 0.570.88
Clinical98%Literature2%

Open Targets aggregate 0.59 · 2 independent evidence families

type 1 diabetes mellitusModerately supported
0.69
agreement 0.530.84
Clinical84%Literature16%

Open Targets aggregate 0.55 · 2 independent evidence families

type 2 diabetes mellitusModerately supported
0.55
agreement 0.400.71
Clinical80%Literature20%

Open Targets aggregate 0.42 · 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 underlying per-type scores are shown above so the calculation can be checked.

What's happening now

29

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

  1. Product recall2026-06-23

    Recall (Not Yet Classified): GLUCAGON

    fda · safety · fda · via Glucagon

  2. Product recall2026-06-23

    Recall (Class II): GLUCAGON

    fda · safety · fda · via Glucagon

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

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

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

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

  5. 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

  6. 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

  7. 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

  8. New publication2023-12-21
    GLP-1 metabolite GLP-1(9-36) is a systemic inhibitor of mouse and human pancreatic islet glucagon secretion.

    Diabetologia · 2024 · 20 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. New publication2023-09-08
    Metabolic regulation of glucagon secretion.

    The Journal of endocrinology · 2023 · 20 citations · Europe PMC · via Glucagon

  12. New publication2023-08-11
    The role of glucagon after bariatric/metabolic surgery: much more than an "anti-insulin" hormone.

    Frontiers in endocrinology · 2023 · 3 citations · Europe PMC · 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.