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Research Catalog

Molecular mechanism

Glucagon-like peptide-1 receptor

GLP-1R is a class B G-protein-coupled receptor. The cited structural and pharmacology records characterize semaglutide and retatrutide as peptide agonists at this receptor.

Type: receptorPublished: 2026-09-04Literature/identifier verification: 2026-08-23

See this target on the receptor map

GLP-1R

01

Neutral molecular overview

GLP-1R is a class B G-protein-coupled receptor. The cited structural and pharmacology records characterize semaglutide and retatrutide as peptide agonists at this receptor.

02

Target identifiers

No target identifier beyond the verified name and aliases is listed for this mechanism.

03

Related compounds

Compound

Exenatide

Exenatide is synthetic exendin-4, a 39-residue peptide with an N-terminal histidine and a C-terminal serine amide; the natural peptide was isolated from Heloderma suspectum venom and characterized as a member of the glucagon superfamily. Horváth et al. (PMID 37528104) place the exendins among the gastrointestinal peptides of the glucagon family.

Compound

GLP-1(7-36) amide

GLP-1(7-36) amide is an endogenous processing form of glucagon-like peptide-1 and the native ligand against which the GLP-1 receptor agonists in this library are compared. Deacon et al. (PMID 7556682) isolated this form from human colon and conclude that it is a product of proglucagon processing. Horváth et al. (PMID 37528104) place GLP-1 among the gastrointestinal peptides of the glucagon family.

Compound

GLP-1(7-37)

GLP-1(7-37) is an endogenous processing form of glucagon-like peptide-1 retaining a C-terminal glycine, and the structural reference for several acylated GLP-1 analogs. Mojsov et al. (PMID 3543057) describe the glucagon-like peptides as liberated from proglucagon in both the pancreas and the intestine. Horváth et al. (PMID 37528104) place GLP-1 among the gastrointestinal peptides of the glucagon family.

Compound

Liraglutide

Liraglutide is an acylated peptide analog of glucagon-like peptide-1, characterized against the GLP-1 receptor.

Compound

Mazdutide

Mazdutide is a lipidated synthetic peptide classified as a GLP-1 and glucagon receptor dual agonist, built on an oxyntomodulin-derived backbone.

Compound

Orforglipron

Orforglipron is a synthetic nonpeptide molecule characterized as a selective, high-affinity agonist at the human GLP-1 receptor.

Compound

Oxyntomodulin

Oxyntomodulin is an endogenous proglucagon-derived peptide containing the complete glucagon sequence plus an eight-residue C-terminal extension, with reported activity at both the GLP-1 and glucagon receptors. A review by Bataille and Dalle (PMID 25115338) describes oxyntomodulin as a member of the glucagon family; that is a review-level family attribution.

Compound

Retatrutide

Retatrutide, development code LY3437943, is a single peptide characterized as an agonist at GCGR, GIPR, and GLP-1R in its discovery record.

Compound

Semaglutide

Semaglutide is an acylated peptide analog of glucagon-like peptide-1. Its discovery record identifies two amino-acid substitutions and derivatization at Lys26.

Compound

Survodutide

Survodutide is a lipidated synthetic peptide agonist at both the GLP-1 receptor and the glucagon receptor, built on a modified glucagon-family backbone with a branched side-chain linker.

Compound

Tirzepatide

Tirzepatide is a fatty-acid-modified synthetic peptide characterized in its discovery record as having agonist activity at both the GIP receptor and the GLP-1 receptor.

04

Related mechanisms

receptor

Glucose-dependent insulinotropic polypeptide receptor

GIPR is a class B G-protein-coupled receptor. The cited discovery and trial records identify it as one of the three receptor relationships declared for retatrutide.

receptor

Glucagon receptor

GCGR is a class B G-protein-coupled receptor. Retatrutide's LY3437943 discovery record characterizes a molecular agonist relationship at GCGR alongside GIPR and GLP-1R.

05

Verified bibliography

  1. Reference 1

    Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide.

    Lau J, Bloch P, Schäffer L, Pettersson I, Spetzler J, Kofoed J, Madsen K, Knudsen LB, McGuire J, Steensgaard DB, Strauss HM, Gram DX, Knudsen SM, Nielsen FS, Thygesen P, Reedtz-Runge S, Kruse T

    Journal of medicinal chemistry · 2015-09-11 · Journal Article

    current
    PMID 26308095DOI 10.1021/acs.jmedchem.5b00726SemaglutideGLP-1R

  2. Reference 2

    Structure and dynamics of semaglutide- and taspoglutide-bound GLP-1R-Gs complexes.

    Zhang X, Belousoff MJ, Liang YL, Danev R, Sexton PM, Wootten D

    Cell reports · 2021-07-13 · Journal Article

    current
    PMID 34260945DOI 10.1016/j.celrep.2021.109374SemaglutideGLP-1R

  3. Reference 3

    The Discovery and Development of Liraglutide and Semaglutide.

    Knudsen LB, Lau J

    Frontiers in endocrinology · 2019-04-12 · Review

    current
    PMID 31031702PMC6474072DOI 10.3389/fendo.2019.00155SemaglutideGLP-1R

  4. Reference 4

    LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept.

    Coskun T, Urva S, Roell WC, Qu H, Loghin C, Moyers JS, O'Farrell LS, Briere DA, Sloop KW, Thomas MK, Pirro V, Wainscott DB, Willard FS, Abernathy M, Morford L, Du Y, Benson C, Gimeno RE, Haupt A, Milicevic Z

    Cell metabolism · 2022-08-18 · Journal Article

    current
    PMID 35985340DOI 10.1016/j.cmet.2022.07.013RetatrutideGLP-1RGIPRGCGR

  5. Reference 5

    Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial.

    Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML, Retatrutide Phase 2 Obesity Trial Investigators

    The New England journal of medicine · 2023-06-26 · Clinical Trial, Phase II

    current
    PMID 37366315DOI 10.1056/NEJMoa2301972RetatrutideGLP-1RGIPRGCGR

  6. Reference 6

    Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA.

    Rosenstock J, Frias J, Jastreboff AM, Du Y, Lou J, Gurbuz S, Thomas MK, Hartman ML, Haupt A, Milicevic Z, Coskun T

    Lancet (London, England) · 2023-06-26 · Clinical Trial, Phase II

    current
    PMID 37385280DOI 10.1016/S0140-6736(23)01053-XRetatrutideGLP-1RGIPRGCGR

  7. Reference 7

    Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.

    Sanyal AJ, Kaplan LM, Frias JP, Brouwers B, Wu Q, Thomas MK, Harris C, Schloot NC, Du Y, Mather KJ, Haupt A, Hartman ML

    Nature medicine · 2024-06-10 · Clinical Trial, Phase II

    current
    PMID 38858523PMC11271400DOI 10.1038/s41591-024-03018-2RetatrutideGLP-1RGIPRGCGR

  8. Reference 8

    Pharmacology, physiology, and mechanisms of incretin hormone action.

    Campbell JE, Drucker DJ

    Cell metabolism · 2013-05-16 · Review

    current
    PMID 23684623DOI 10.1016/j.cmet.2013.04.008TirzepatideSemaglutideRetatrutideExenatideLiraglutideGLP-1RGIPR

  9. Reference 9

    Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein.

    Zhang Y, Sun B, Feng D, Hu H, Chu M, Qu Q, Tarrasch JT, Li S, Sun Kobilka T, Kobilka BK, Skiniotis G

    Nature · 2017-05-24 · Journal Article

    current
    PMID 28538729PMC5587415DOI 10.1038/nature22394SemaglutideLiraglutideExenatideTirzepatideRetatrutideGLP-1R

  10. Reference 10

    Structural basis for ligand recognition of incretin receptors.

    Underwood CR, Parthier C, Reedtz-Runge S

    Vitamins and hormones · 2010 · Review

    current
    PMID 21094903DOI 10.1016/B978-0-12-381517-0.00009-6SemaglutideLiraglutideExenatideTirzepatideRetatrutideGLP-1RGIPR

  11. Reference 11

    Full-length human GLP-1 receptor structure without orthosteric ligands.

    Wu F, Yang L, Hang K, Laursen M, Wu L, Han GW, Ren Q, Roed NK, Lin G, Hanson MA, Jiang H, Wang MW, Reedtz-Runge S, Song G, Stevens RC

    Nature communications · 2020-03-09 · Journal Article

    current
    PMID 32152292PMC7062719DOI 10.1038/s41467-020-14934-5GLP-1R

  12. Reference 12

    Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist.

    Kawai T, Sun B, Yoshino H, Feng D, Suzuki Y, Fukazawa M, Nagao S, Wainscott DB, Showalter AD, Droz BA, Kobilka TS, Coghlan MP, Willard FS, Kawabe Y, Kobilka BK, Sloop KW

    Proceedings of the National Academy of Sciences of the United States of America · 2020-11-11 · Journal Article

    current
    PMID 33177239PMC7703558DOI 10.1073/pnas.2014879117LiraglutideOrforglipronGLP-1R

  13. Reference 13

    BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy.

    Zimmermann T, Thomas L, Baader-Pagler T, Haebel P, Simon E, Reindl W, Bajrami B, Rist W, Uphues I, Drucker DJ, Klein H, Santhanam R, Hamprecht D, Neubauer H, Augustin R

    Molecular metabolism · 2022-11-07 · Journal Article

    current
    PMID 36356832PMC9679702DOI 10.1016/j.molmet.2022.101633SurvodutideGlucagonGLP-1RGCGR

  14. Reference 14

    The dual GCGR/GLP-1R agonist survodutide: Biomarkers and pharmacological profiling for clinical candidate selection.

    Thomas L, Martel E, Rist W, Uphues I, Hamprecht D, Neubauer H, Augustin R

    Diabetes, obesity & metabolism · 2024-04-01 · Journal Article

    current
    PMID 38560764DOI 10.1111/dom.15551SurvodutideGLP-1RGCGR

  15. Reference 15

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

    Li Y, Zhou Q, Dai A, Zhao F, Chang R, Ying T, Wu B, Yang D, Wang MW, Cong Z

    Proceedings of the National Academy of Sciences of the United States of America · 2023-08-07 · Journal Article

    current
    PMID 37549266PMC10438375DOI 10.1073/pnas.2303696120SurvodutideMazdutideGLP-1RGCGR

  16. Reference 16

    Evaluation of biased agonism mediated by dual agonists of the GLP-1 and glucagon receptors.

    Darbalaei S, Yuliantie E, Dai A, Chang R, Zhao P, Yang D, Wang MW, Sexton PM, Wootten D

    Biochemical pharmacology · 2020-07-17 · Journal Article

    current
    PMID 32682761DOI 10.1016/j.bcp.2020.114150MazdutideGLP-1RGCGR

  17. Reference 17

    Partial agonism improves the anti-hyperglycaemic efficacy of an oxyntomodulin-derived GLP-1R/GCGR co-agonist.

    Pickford P, Lucey M, Rujan RM, McGlone ER, Bitsi S, Ashford FB, Corrêa IR, Hodson DJ, Tomas A, Deganutti G, Reynolds CA, Owen BM, Tan TM, Minnion J, Jones B, Bloom SR

    Molecular metabolism · 2021-04-30 · Journal Article

    current
    PMID 33933675PMC8163982DOI 10.1016/j.molmet.2021.101242MazdutideGLP-1RGCGR

  18. Reference 18

    Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas.

    Eng J, Kleinman WA, Singh L, Singh G, Raufman JP

    The Journal of biological chemistry · 1992-04-15 · Journal Article

    current
    PMID 1313797ExenatideGLP-1R

  19. Reference 19

    Exendin peptides.

    Eng J

    The Mount Sinai journal of medicine, New York · 1992-03 · Journal Article

    current
    PMID 1574068ExenatideGLP-1R

  20. Reference 20

    The arcuate nucleus mediates GLP-1 receptor agonist liraglutide-dependent weight loss.

    Secher A, Jelsing J, Baquero AF, Hecksher-Sørensen J, Cowley MA, Dalbøge LS, Hansen G, Grove KL, Pyke C, Raun K, Schäffer L, Tang-Christensen M, Verma S, Witgen BM, Vrang N, Bjerre Knudsen L

    The Journal of clinical investigation · 2014-09-09 · Journal Article

    current
    PMID 25202980PMC4215190DOI 10.1172/JCI75276LiraglutideGLP-1R

  21. Reference 21

    LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept.

    Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS, Benson CT, Gimeno RE, D'Alessio DA, Haupt A

    Molecular metabolism · 2018-10-03 · Journal Article

    current
    PMID 30473097PMC6308032DOI 10.1016/j.molmet.2018.09.009TirzepatideGIPRGLP-1R

  22. Reference 22

    Semaglutide lowers body weight in rodents via distributed neural pathways.

    Gabery S, Salinas CG, Paulsen SJ, Ahnfelt-Rønne J, Alanentalo T, Baquero AF, Buckley ST, Farkas E, Fekete C, Frederiksen KS, Helms HCC, Jeppesen JF, John LM, Pyke C, Nøhr J, Lu TT, Polex-Wolf J, Prevot V, Raun K, Simonsen L, Sun G, Szilvásy-Szabó A, Willenbrock H, Secher A, Knudsen LB, Hogendorf WFJ

    JCI insight · 2020-03-26 · Journal Article

    current
    PMID 32213703PMC7213778DOI 10.1172/jci.insight.133429SemaglutideGLP-1R

  23. Reference 23

    How May GIP Enhance the Therapeutic Efficacy of GLP-1?

    Samms RJ, Coghlan MP, Sloop KW

    Trends in endocrinology and metabolism: TEM · 2020-03-16 · Review

    current
    PMID 32396843DOI 10.1016/j.tem.2020.02.006TirzepatideGIPRGLP-1R

  24. Reference 24

    Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist.

    Willard FS, Douros JD, Gabe MB, Showalter AD, Wainscott DB, Suter TM, Capozzi ME, van der Velden WJ, Stutsman C, Cardona GR, Urva S, Emmerson PJ, Holst JJ, D'Alessio DA, Coghlan MP, Rosenkilde MM, Campbell JE, Sloop KW

    JCI insight · 2020-09-03 · Journal Article

    current
    PMID 32730231PMC7526454DOI 10.1172/jci.insight.140532TirzepatideGIPRGLP-1R

  25. Reference 25

    Structural determinants of dual incretin receptor agonism by tirzepatide.

    Sun B, Willard FS, Feng D, Alsina-Fernandez J, Chen Q, Vieth M, Ho JD, Showalter AD, Stutsman C, Ding L, Suter TM, Dunbar JD, Carpenter JW, Mohammed FA, Aihara E, Brown RA, Bueno AB, Emmerson PJ, Moyers JS, Kobilka TS, Coghlan MP, Kobilka BK, Sloop KW

    Proceedings of the National Academy of Sciences of the United States of America · 2022-03-25 · Journal Article

    current
    PMID 35333651PMC9060465DOI 10.1073/pnas.2116506119TirzepatideGIPRGLP-1R

  26. Reference 26

    The pharmacological basis for nonpeptide agonism of the GLP-1 receptor by orforglipron.

    Sloop KW, Cox AL, Wainscott DB, White A, Droz BA, Stutsman C, Showalter AD, Suter TM, Dunbar JD, Snider BM, O'Farrell LS, Hewitt N, Ruble JC, Padgett LR, Woerly EM, Peterson JA, Coskun T, Liu Z, Coutant DE, Ai M, Emmerson PJ, Sangwung P, Willard FS

    Science translational medicine · 2024-12-18 · Journal Article

    current
    PMID 39693407DOI 10.1126/scitranslmed.adp5765OrforglipronGLP-1R

  27. Reference 27

    The glucagon receptor is involved in mediating the body weight-lowering effects of oxyntomodulin.

    Kosinski JR, Hubert J, Carrington PE, Chicchi GG, Mu J, Miller C, Cao J, Bianchi E, Pessi A, Sinharoy R, Marsh DJ, Pocai A

    Obesity (Silver Spring, Md.) · 2012-03-16 · Journal Article

    current
    PMID 22421924PMC3408645DOI 10.1038/oby.2012.67OxyntomodulinGLP-1RGCGR

Study models of these references

What kind of experiment each cited paper reports, taken from its abstract unless marked. Not a summary of results.

ReferenceStudy models
Lau J et al. 2015Study models reported: in vitro; animal (mini-pig) · from the abstract
Zhang X et al. 2021Study models reported: in vitro · from the abstract
Knudsen LB et al. 2019Review article
Coskun T et al. 2022Study models reported: in vitro; animal (mouse); human participants (interventional) · from the abstract
Jastreboff AM et al. 2023Study models reported: human participants (interventional) · from the abstract
Rosenstock J et al. 2023Study models reported: human participants (interventional) · from the abstract
Sanyal AJ et al. 2024Study models reported: human participants (interventional) · from the abstract
Campbell JE et al. 2013Review article
Zhang Y et al. 2017Study models reported: in vitro · from the abstract
Underwood CR et al. 2010Review article
Wu F et al. 2020Study models reported: in vitro · from the abstract
Kawai T et al. 2020Study models reported: in vitro; animal (mouse, rat, cynomolgus monkey) · from the full text
Zimmermann T et al. 2022Study models reported: in vitro; animal (mouse, beagle dog) · from the full text
Thomas L et al. 2024Study models reported: in vitro; animal (mouse) · from the abstract
Li Y et al. 2023Study models reported: in vitro · from the abstract
Darbalaei S et al. 2020Study models reported: in vitro · from the abstract
Pickford P et al. 2021Study models reported: in vitro; animal (mouse) · from the abstract
Eng J et al. 1992Study models reported: in vitro · from the abstract
Eng J 1992Study type not determinable from the abstract
Secher A et al. 2014Study models reported: in vitro; animal (rat, mouse) · from the abstract
Coskun T et al. 2018Study models reported: in vitro; animal (mouse); human participants (interventional) · from the abstract
Gabery S et al. 2020Study models reported: in vitro; animal (rat, mouse) · from the full text
Samms RJ et al. 2020Review article
Willard FS et al. 2020Study models reported: in vitro · from the full text
Sun B et al. 2022Study models reported: in vitro · from the abstract
Sloop KW et al. 2024Study models reported: in vitro; animal (mouse, rat) · from the abstract
Kosinski JR et al. 2012Study models reported: in vitro; animal (mouse) · from the full text

06

Related glossary terms

AgonistLigandG-protein-coupled receptor

07

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