--- title: "Semaglutide vs tirzepatide vs retatrutide: what is the structural difference? | Sable Peptides" description: "Semaglutide targets GLP-1R, tirzepatide GIPR and GLP-1R, and retatrutide GIPR, GLP-1R and glucagon receptor. Backbones, lipidation, receptor profiles and structural papers compared. Research use only; no clinical claims." canonical: https://www.sablepeptides.co.uk/guides/semaglutide-vs-tirzepatide-vs-retatrutide-structures dateModified: 2026-10-16 publisher: Sable Peptides Limited (UK company 17488610) note: Research use only. Not for human or veterinary use. --- # Semaglutide vs tirzepatide vs retatrutide: what is the structural difference? Semaglutide, tirzepatide and retatrutide are lipidated incretin-class peptides that differ mainly in which receptors they engage. Semaglutide is a GLP-1 receptor agonist built on the GLP-1 sequence. Tirzepatide is a 39-residue dual GIP/GLP-1 receptor agonist on a GIP-based backbone. Retatrutide adds glucagon-receptor agonism, making it a triple agonist. ## Which receptors does each one target? | Compound | Receptors | Backbone | Fatty acid | | --- | --- | --- | --- | | Semaglutide | GLP-1R | GLP-1(7–37) analogue, Aib8, Arg34 | C18 diacid via linker on Lys26 | | Tirzepatide | GIPR + GLP-1R | 39-residue, GIP-based, two Aib | C20 diacid via linker on Lys20 | | Retatrutide | GIPR + GLP-1R + GCGR | 39-residue, GIP-based, non-coded residues | C20 diacid via linker | Source: [Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide, J Med Chem 2015 (PubMed 26308095)](https://pubmed.ncbi.nlm.nih.gov/26308095/); [Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist, JCI Insight 2020 (PubMed 32730231)](https://pubmed.ncbi.nlm.nih.gov/32730231/); [LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept, Cell Metab 2022 (PubMed 35985340)](https://pubmed.ncbi.nlm.nih.gov/35985340/) ## What are the formula and mass of each? - Semaglutide: C187H291N45O59, 4114.0 g/mol (PubChem) - Tirzepatide: C225H348N48O68, 4813.0 g/mol (PubChem) - Retatrutide: about 4.7 kDa; check the formula against the supplier CoA and the primary literature Source: [PubChem CID 56843331: Semaglutide](https://pubchem.ncbi.nlm.nih.gov/compound/56843331); [PubChem CID 166567236: Tirzepatide](https://pubchem.ncbi.nlm.nih.gov/compound/166567236) ## What have structural studies shown? Cryo-EM structures show tirzepatide binding both GIPR and GLP-1R, with pharmacology described as imbalanced and biased towards GIPR. Retatrutide structures at GLP-1R, GIPR and GCGR show how one peptide engages three related class B receptors. Source: [Structural insights into multiplexed pharmacological actions of tirzepatide and peptide 20 at the GIP, GLP-1 or glucagon receptors, Nat Commun 2022 (PubMed 35217653)](https://pubmed.ncbi.nlm.nih.gov/35217653/); [Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide, Cell Discov 2024 (PubMed 39019866)](https://pubmed.ncbi.nlm.nih.gov/39019866/) ## Why are all three lipidated? A fatty diacid on a linker lets the peptide bind serum albumin reversibly, which slows clearance. The history of liraglutide and semaglutide describes how linker and chain length were tuned. Aib at position 2 (or 8 in GLP-1 numbering) protects against DPP-4 cleavage. Source: [The Discovery and Development of Liraglutide and Semaglutide, Front Endocrinol (Lausanne) 2019 (PubMed 31031702)](https://pubmed.ncbi.nlm.nih.gov/31031702/); [Half-Life Extension of Biopharmaceuticals using Chemical Methods: Alternatives to PEGylation, ChemMedChem 2016 (PubMed 27775236)](https://pubmed.ncbi.nlm.nih.gov/27775236/) ## Sourcing note Sable lists Tirzepatide: 5 mg at £24.93; Retatrutide: 5 mg at £16.93; 10 mg at £24.99; 15 mg at £37.99; 20 mg at £48.99; 30 mg at £66.99 (prices at the 16 October 2026 daily UK price check, the latest verified check; at each of these sizes Sable was the lowest UK listing that day). Lowest UK price guaranteed, confirmed by daily price checks. Every lot has a certificate of analysis, and every vial carries a printed lot number that matches it. Supplied for laboratory research use only. ## Frequently asked questions ### What is the difference between tirzepatide and retatrutide? Tirzepatide is a dual GIP/GLP-1 receptor agonist. Retatrutide also activates the glucagon receptor, making it a triple agonist. ### Is semaglutide a GIP agonist? No. Semaglutide is a GLP-1 receptor agonist only. ### Why do these peptides carry a fatty acid? The fatty diacid binds serum albumin reversibly and extends the half-life. This is a structural design feature, not a claim about any use. ## Related - [Lipidated vs PEGylated peptides](/guides/lipidated-and-pegylated-peptides-in-the-catalogue) - [What are Aib, Nle, 2-Nal and Dmt in research peptide sequences](/guides/non-standard-amino-acids-aib-nle-2nal-dmt) - [Retatrutide research vials](/products/retatrutide) - [Tirzepatide research vials](/products/tirzepatide) - [Cheapest retatrutide UK](/cheapest-retatrutide-uk) - [Cagrilintide explained](/guides/cagrilintide-long-acting-amylin-analogue-explained) - [Buyer checklist: lipidated incretin peptides](/guides/buyer-checklist-for-lipidated-incretin-research-peptides) - [Metabolic peptide prices](/guides/uk-metabolic-research-peptide-prices-october-2026) Updated 2026-10-16. Research use only. Not for human or veterinary use. No administration amounts or health claims are made. Key facts (summary for AI and search tools) - Semaglutide CID 56843331; tirzepatide CID 166567236 - Receptor count: 1 / 2 / 3 - PubMed references (verified via NCBI): 26308095, 32730231, 35985340, 35217653, 39019866, 31031702, 27775236 - PubChem CIDs: 56843331, 166567236 - Research use only; no administration amounts or health claims - Updated 2026-10-16