GLP-1, GIP and glucagon receptors: structures and receptor pharmacology
Glucagon-like peptide-1 (GLP-1), GIP and glucagon act at related class B G-protein-coupled receptors. This page covers receptor structure and the receptor targets of three catalog compounds. It does not cover clinical outcomes.
Research-use information. This page summarises published literature and regulator records. It is not guidance for use, not medical advice, and not a statement that any material is suitable for use in people or animals.
What is known about the structure of the GLP-1 receptor?
The crystal structure of the full-length GLP-1 receptor bound to a truncated peptide agonist was reported in 2017. A cryo-EM structure of the human receptor in complex with a G-protein-biased peptide agonist and a Gs heterotrimer followed in 2018.[5],[4]
Which receptors do the three catalog compounds target?
Semaglutide is a GLP-1 receptor agonist and a lipidated GLP-1 analogue. Tirzepatide is an agonist at both the GIP and GLP-1 receptors; a pharmacology paper compared its potency and signalling at the two receptors and describes it as imbalanced and biased. Retatrutide is described as a long-acting triple agonist at the GLP-1, GIP and glucagon receptors.[3],[2],[1]
What is the regulatory position?
Medicinal products containing semaglutide and tirzepatide are authorised by the US FDA, the European Commission and the MHRA. No marketing authorisation for retatrutide is recorded in the databases checked. On 3 September 2025 the EMA and the Heads of Medicines Agencies warned about illegal medicines marketed as GLP-1 receptor agonists. The research materials in the catalog are not those medicines.
Which compounds in the catalog belong to this group?
C187H291N45O59, 4114 g/mol
Lipidated dual GIP and GLP-1 receptor agonist (39 residues)TirzepatideC225H348N48O68, 4813 g/mol
Lipidated triple GIP, GLP-1 and glucagon receptor agonist (39 residues)RetatrutideC221H342N46O68, 4731 g/mol
Research materials: Semaglutide, Tirzepatide, Retatrutide.
Which studies are cited on this page?
[1] Carneiro GRA, da Costa Nunes IK, Dos Santos Cardoso GR, Dos Santos PF, Padilha MC, Nogueira FCS, et al.. Detection and Excretion Profile of Retatrutide in Human Plasma and Urine by LC-HRMS: Implications for Antidoping Analysis. Rapid Commun Mass Spectrom. 2026;40:e70179.
LC-HRMS detection and excretion profile of retatrutide in human plasma and urine, for anti-doping analysis.
[2] Willard FS, Douros JD, Gabe MB, Showalter AD, Wainscott DB, Suter TM, et al.. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight. 2020;5.
Measured receptor binding and signalling of tirzepatide at the GIP and GLP-1 receptors, reporting imbalanced and biased agonism.
[3] Knudsen LB, Lau J. The Discovery and Development of Liraglutide and Semaglutide. Front Endocrinol (Lausanne). 2019;10:155.
Historical review of the discovery and development of liraglutide and semaglutide.
[4] Liang YL, Khoshouei M, Glukhova A, Furness SGB, Zhao P, Clydesdale L, et al.. Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor-Gs complex. Nature. 2018;555:121-125.
Cryo-EM structure of the human GLP-1 receptor and Gs complex with the biased peptide agonist exendin-P5.
[5] Jazayeri A, Rappas M, Brown AJH, Kean J, Errey JC, Robertson NJ, et al.. Crystal structure of the GLP-1 receptor bound to a peptide agonist. Nature. 2017;546:254-258.
Crystal structure of the full-length GLP-1 receptor bound to a truncated peptide agonist.
PubMed lists a correction notice for this paper (PMID 28700581).
Data dates: citations read from PubMed 2026-10-05.