Protein / target

Glucagon-like peptide 1 receptor

Encoded byGLP1RP43220Homo sapiensSwiss-Prot

UniProt: P43220 Ensembl: ENSG00000112164 HGNC: HGNC:4324 NCBI Gene: 2740

Clinically validated

Therapeutic maturity

Approved medicines

Open Targets target-level

View by indication →

Clinical trials

Small-molecule tractable

Druggability

Advanced Clinical

Protein at a glance

Biological role

Glucagon-like peptide 1 receptor

Strongest disease association

Diabetes Mellitus

Via encoding gene GLP1R · Genetic evidence · score 0.74

Therapeutic position

Established drug target

Small molecules

Research activity

Extensively researched

115 papers · latest 2026

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-like peptide 1 (GLP-1).

View complete UniProt function annotation

G protein-coupled receptor for glucagon-like peptide 1 (GLP-1) (PubMed:19861722, PubMed:26308095, PubMed:27196125, PubMed:28514449, PubMed:7517895, PubMed:8216285, PubMed:8405712). Ligand binding triggers activation of a signaling cascade that leads to the activation of adenylyl cyclase and increased intracellular cAMP levels (PubMed:19861722, PubMed:26308095, PubMed:27196125, PubMed:28514449, PubMed:7517895, PubMed:8216285, PubMed:8405712). Plays a role in regulating insulin secretion in response to GLP-1 (By similarity)

Subcellular location

Cell membrane

Domains and Gene Ontology detail (14)

Gene Ontology

Cmembrane
Cplasma membrane
Fglucagon receptor activity
Fglucagon-like peptide 1 receptor activity
Fpeptide hormone binding
Ftransmembrane signaling receptor activity
Pactivation of adenylate cyclase activity
Padenylate cyclase-activating G protein-coupled receptor signaling pathway
Pcell surface receptor signaling pathway
Plearning or memory
Ppositive regulation of blood pressure
Ppositive regulation of cytosolic calcium ion concentration

463 aa · 53 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-like peptide 1 (GLP-1) (PubMed:19861722, PubMed:…
·adenylate cyclase-activating G protein-coupled receptor signaling pathway

View underlying pathways (3)

Glucagon-like Peptide-1 (GLP1) regulates insulin secretion

G alpha (s) signalling events

Glucagon-type ligand receptors

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.

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

7 medicines · 4 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 Mellitus7 medicines

albiglutide dulaglutide Exenatide liraglutide lixisenatide semaglutide tirzepatide

Diabetes Mellitus, Type 27 medicines

albiglutide dulaglutide Exenatide liraglutide lixisenatide semaglutide tirzepatide

Obesity3 medicines

liraglutide semaglutide tirzepatide

Overweight3 medicines

liraglutide semaglutide tirzepatide

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

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.

liraglutide

Narrow target profileApprovedAgonist

Glucagon-like peptide 1 receptor agonist

Indicated for Diabetes Mellitus, Diabetes Mellitus, Type 2, Obesity, Overweight

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

semaglutide

Narrow target profileApprovedAgonist

Glucagon-like peptide 1 receptor agonist

Indicated for Diabetes Mellitus, Diabetes Mellitus, Type 2, Obesity, Overweight

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

Exenatide

Narrow target profileApprovedAgonist

Glucagon-like peptide 1 receptor agonist

Indicated for Diabetes Mellitus, Diabetes Mellitus, Type 2

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

exendin (9-39)

Narrow target profileAntagonist

Glucagon-like peptide 1 receptor antagonist

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

lixisenatide

Narrow target profileApprovedAgonist

Glucagon-like peptide 1 receptor agonist

Indicated for Diabetes Mellitus, Diabetes Mellitus, Type 2

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

dulaglutide

Narrow target profileApprovedAgonist

Glucagon-like peptide 1 receptor agonist

Indicated for Diabetes Mellitus, Diabetes Mellitus, Type 2

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

View all 10 targeting drugs

tirzepatide

Narrow target profileApprovedAgonist

Glucagon-like peptide 1 receptor agonist

Indicated for Diabetes Mellitus, Diabetes Mellitus, Type 2, Obesity, Overweight

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

albiglutide

Narrow target profileApprovedAgonist

Glucagon-like peptide 1 receptor agonist

Indicated for Diabetes Mellitus, Diabetes Mellitus, Type 2

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

retatrutide

Narrow target profilePhase 3Agonist

Glucagon-like peptide 1 receptor agonist

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

Efinopegdutide

Narrow target profilePhase 2Agonist

Glucagon-like peptide 1 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 GLP1R

Gene-level evidence surfaced through the gene GLP1Rthat 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.

Diabetes Mellitus, Type 2

0.94Well supported

Clinical evidence dominant · Open Targets 0.76

Diabetes Mellitus

0.94Well supported

Genetic evidence dominant · Open Targets 0.71

Obesity disorder

0.92Well supported

Genetic evidence dominant · Open Targets 0.68

Diabetes Mellitus, Type 1

0.84Well supported

Genetic evidence dominant · Open Targets 0.52

Obesity, Morbid

0.78Well supported

Genetic evidence dominant · Open Targets 0.47

View evidence synthesis (5)

Diabetes Mellitus, Type 2Well supported

0.94

agreement 0.84–1.00

Clinical46%Genetic45%Literature9%

Open Targets aggregate 0.76 · 3 independent evidence families

Diabetes MellitusWell supported

0.94

agreement 0.83–1.00

Genetic46%Clinical45%Literature9%

Open Targets aggregate 0.71 · 3 independent evidence families

Obesity disorderWell supported

0.92

agreement 0.81–1.00

Genetic46%Clinical45%Literature9%

Open Targets aggregate 0.68 · 3 independent evidence families

Diabetes Mellitus, Type 1Well supported

0.84

agreement 0.74–0.95

Genetic50%Clinical40%Literature10%

Open Targets aggregate 0.52 · 3 independent evidence families

Obesity, MorbidWell supported

0.78

agreement 0.67–0.89

Genetic61%Clinical36%Literature3%

Open Targets aggregate 0.47 · 3 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

Diabetes Mellitus, Type 20.76

Diabetes Mellitus0.71

Obesity disorder0.68

Non-alcoholic Fatty Liver Disease0.53

Diabetes Mellitus, Type 10.52

Hyperlipidemias0.47

Obesity, Morbid0.47

Drug development

17 compounds recorded · 7 approved · 10 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 10 drugs that target this protein in Forefront's canonical graph (7 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)

DANUGLIPRONPhase 2

EXENATIDEApproval

COTADUTIDEPhase 2

LIRAGLUTIDEApproval

PEGSEBRENATIDEPhase 2

SEMAGLUTIDEApproval

RETATRUTIDEPhase 3

TASPOGLUTIDEPhase 3

PEGAPAMODUTIDEPhase 2

LIXISENATIDEApproval

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 molecules — Strong

Advanced Clinical and Structure with Ligand support this modality.

Antibodies — Emerging

Feasibility evidence (uniprot loc high conf and go cc high conf) — no clinical-stage drug of this modality recorded.

Protein degraders — Emerging

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

Other modalities — Strong

Approved Drug support this modality.

View underlying tractability evidence (9)

SM · Advanced ClinicalSM · Structure with LigandSM · High-Quality LigandSM · Druggable FamilyAB · 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.

Safety-related annotations

less weight gainClinPGxweight gainClinPGx

Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.

Clinical trials

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.

Multifactorial Intervention to Reduce Cardiovascular Disease in Type 1 DiabetesPHASE3

RECRUITING · via semaglutide · NCT06082063

Effects of the Glucagon Like-peptide 1 (GLP-1) Receptor Agonist Liraglutide on Lower Limb Perfusion in People With Type 2 Diabetes and Peripheral Artery Disease: a Randomized Controlled TrialPHASE4

COMPLETED · via liraglutide · NCT04881110

International, Randomized, Open Label Study to Compare the Safety and Efficacy of Lixisenatide vs. Sulfonylurea on Top of Basal Insulin Treatment in Type 2 Diabetes Mellitus Subjects Who Elect to Fast During RamadanPHASE4

COMPLETED · via lixisenatide · NCT02941367

Safety Evaluation of Adverse Reactions in DiabetesPHASE4

COMPLETED · via Exenatide · NCT02092597

View all trials (26)

Efficacy and Safety of Once-weekly Subcutaneous NNC0662-0419 in Participants With Type 2 Diabetes - a Dose-finding StudyPHASE2

RECRUITING · via semaglutide · NCT07415954

A Phase 2a, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Efficacy, Safety, and Tolerability of ECC4703 as an Adjunct to Semaglutide in Adults With ObesityPHASE2

ACTIVE_NOT_RECRUITING · via semaglutide · NCT07505303

Semaglutide and Dapagliflozin in Diabetic Patients With Different PathophysiologyPHASE2

ACTIVE_NOT_RECRUITING · via semaglutide · NCT04451837

Effects of GLP-l Receptor Agonists on Cardiometabolic Alterations in HIV-associated LipohypertrophyPHASE2

ACTIVE_NOT_RECRUITING · via semaglutide · NCT04019197

Open-label, Randomised, 4 Parallel-group, Phase I Clinical Trial to Investigate BI 456906 Occupancy of Glucagon Receptors in Liver and Glucagon-like Peptide 1 Receptors in Pancreas in Comparison With Semaglutide After Administration of Radiolabeled Tracer in Male and Female Subjects With Obesity Using PET and MRIPHASE1

RECRUITING · via semaglutide · NCT05202353

Optimizing Stage 2 T1DM Management: Assessing the Impact of GLP-1Ra on Metabolic Outcomes in Patients Receiving TeplizumabEARLY_PHASE1

RECRUITING · via semaglutide · NCT06338553

An Interventional Study Investigating the Effects of Probiotics on Body Weight and Metabolic HomeostasisNA

RECRUITING · via semaglutide · NCT06989177

Adipose Tissue Heterogeneity and Its Link to Type 2 Diabetes: A Randomized Open Intervention Study That Compares Empagliflozin, Pioglitazone and SemaglutideNA

RECRUITING · via semaglutide · NCT05501483

The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging in Older Overweight/Obese Adults With Insulin ResistancePHASE4

COMPLETED · via semaglutide · NCT05786521

Effectiveness of Semaglutide 2.4 mg vs. Commercially Available Medications for Chronic Weight Management in Participants With Obesity in a Multi-employer Setting in The US - a Pragmatic Clinical StudyPHASE4

COMPLETED · via semaglutide · NCT05579249

Glucagon-like Peptide-1 Receptor (GLP-1R) Analogue Assisted Rapid Weight Loss Program as Treatment of Idiopathic Intracranial HypertensionPHASE4

COMPLETED · via semaglutide · NCT06027567

An ObEsity-centric Approach With and Without Anti-obesity Medications ComPared to the Usual-care ApprOach to Management of Patients With Obesity and Type 2 Diabetes in an Employer Setting: A Pragmatic Randomized Controlled TrialPHASE4

TERMINATED · via liraglutide · NCT04531176

A Trial to Complare the Injection Site Pain Experience of Semaglutide 0.25 mg and Dulaglutide 0.75 mg Administered scPHASE4

COMPLETED · via semaglutide · NCT04189848

Effects of Liraglutide on Epicardial Fat Pro-Inflammatory Genes in Type 2 Diabetes and Coronary Artery DiseasePHASE4

COMPLETED · via liraglutide · NCT03260881

EFFECTIVENESS AND COST OF INTEGRATING A PROTOCOL WITH USE OF LIRAGLUTIDE 3.0 MG INTO AN OBESITY SERVICE: (STRIVE Study)PHASE4

COMPLETED · via liraglutide · NCT03036800

Clinical Efficacy and Safety of Using 3.0mg Liraglutide to Treat Weight Regain After Roux-en-Y Gastric Bypass SurgeryPHASE4

COMPLETED · via liraglutide · NCT03048578

Cardiovascular Effects of GLP-1 Receptor ActivationPHASE4

COMPLETED · via liraglutide · NCT03101930

Impact of Liraglutide 3.0 on Body Fat Distribution, Visceral Adiposity, and Cardiometabolic Risk Markers In Overweight and Obese Adults at High Risk for Cardiovascular DiseasePHASE4

COMPLETED · via liraglutide · NCT03038620

Combining Lifestyle Modification and Liraglutide to Improve Weight Loss and Health OutcomesPHASE4

COMPLETED · via liraglutide · NCT02911818

Efficacy in Controlling Glycaemia With Victoza® (Liraglutide) as add-on to Metformin vs. OADs as add-on to Metformin After up to 104 Weeks of Treatment in Subjects With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy and Treated in a Primary Care SettingPHASE4

COMPLETED · via liraglutide · NCT02730377

The Effect of Liraglutide Treatment on Postprandial Chylomicron and VLDL Kinetics, Liver Fat and de Novo Lipogenesis - a Single-center Randomized Controlled StudyPHASE4

COMPLETED · via liraglutide · NCT02765399

Effect of Liraglutide on Epicardial Fat in Subjects With Type 2 DiabetesPHASE4

COMPLETED · via liraglutide · NCT02014740

An Individualized treatMent aPproach for oldER patIents: A Randomized, Controlled stUdy in Type 2 Diabetes Mellitus (IMPERIUM)PHASE4

TERMINATED · via liraglutide · NCT02072096

The Efficacy and Safety of Liraglutide Compared to Sitagliptin, Both in Combination With Metformin in Chinese Subjects With Type 2 Diabetes.(LIRA-DPP-4 CHINA™)PHASE4

COMPLETED · via liraglutide · NCT02008682

Cross-over, Double-blind, Unicentric, 52 Week Trial of Liraglutide in Type 1 Diabetes.PHASE4

COMPLETED · via liraglutide · NCT01787916

Liraglutide in Obesity and Diabetes: Identification of CNS Targets Using fMRIPHASE4

COMPLETED · via liraglutide · NCT01562678

ClinicalTrials.gov via the drug-target graph.

What's happening now

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 4 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.

Trial status changed2026-08-10
A Randomized, Double-blind, Placebo-controlled, Parallel-group Phase II Study to Evaluate the Efficacy and Safety of CS060380 Tablets in Patients With Metabolic Dysfunction-associated Steatohepatitis (MASH) and Obesity.
Status changed to Active, not recruiting · ClinicalTrials.gov · via semaglutide
Trial status changed2026-07-30
A Phase III,Multicenter,Randomized,Open-label,Parallel-controlled Study Comparing the Efficacy and Safety of HRS9531 With Semaglutide in Subjects With Type 2 Diabetes Mellitus Not Adequately Controlled With Metformin Monotherapy or in Combination With SGLT2 Inhibitors
Status changed to Completed · ClinicalTrials.gov · via semaglutide
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
Regulatory approval2026-07-15
Approval: Ablymico (EMA)
ema · regulatory · ema · via liraglutide
Regulatory approval2026-07-15
Approval: Liraglutide STADA (EMA)
ema · regulatory · ema · via liraglutide
Regulatory approval2026-07-01
Approval: LIRAGLUTIDE (ANDA212972)
fda · regulatory · fda · via liraglutide
Regulatory approval2026-06-15
Approval: LIRAGLUTIDE (ANDA213155)
fda · regulatory · fda · via liraglutide
New publication2026-03-19
Efficacy and safety of oral semaglutide 14 mg (flexible dose) in early-stage symptomatic Alzheimer's disease (evoke and evoke+): two phase 3, randomised, placebo-controlled trials.
Lancet (London, England) · 2026 · 1 citation · Europe PMC · via semaglutide
New publication2026-03-02
Bimagrumab plus semaglutide alone or in combination for the treatment of obesity: a randomized phase 2 trial.
Nature medicine · 2026 · 10 citations · Europe PMC · via semaglutide
Safety communication2026-02-05
Drug Safety Update: Semaglutide (Wegovy, Ozempic and Rybelsus): risk of Non-arteritic Anterior Ischemic Optic Neuropathy (NAION)
mhra · safety · mhra · via semaglutide
New publication2026-01-14
Glucagon-like receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits.
Lancet (London, England) · 2026 · 9 citations · Europe PMC · via semaglutide
New publication2025-12-19
The Roles of Incretin Hormones GIP and GLP-1 in Metabolic and Cardiovascular Health: A Comprehensive Review.
International journal of molecular sciences · 2025 · 3 citations · Europe PMC · via tirzepatide

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.