Retatrutide vs Tirzepatide vs Semaglutide
Three peptides, one family
Retatrutide, Tirzepatide and Semaglutide are synthetic peptides built on the incretin hormones GLP-1 and GIP. They differ in how many receptors one chain binds: Semaglutide binds the GLP-1 receptor, Tirzepatide binds the GIP and GLP-1 receptors, and Retatrutide binds the GIP, GLP-1 and glucagon receptors. All three carry a fatty diacid on a lysine side chain and non-coded amino acids such as Aib in the chain. This guide compares their structures. It makes no claims about use in people.
Side by side
| Retatrutide | Tirzepatide | Semaglutide | |
|---|---|---|---|
| Developer code | LY3437943 | LY3298176 | NN9535 |
| Developer | Eli Lilly | Eli Lilly | Novo Nordisk |
| Length | 39 amino acids | 39 amino acids | 31 amino acids |
| Base hormone | GIP | GIP | GLP-1(7–37) |
| Receptor targets | GIP, GLP-1, glucagon | GIP, GLP-1 | GLP-1 |
| Non-coded amino acids | Two Aib, one α-methyl-leucine | Aib at positions 2 and 13 | Aib at position 8 (and Arg at 34) |
| Fatty diacid | C20 on a lysine | C20 on lysine 20 | C18 on lysine 26 |
| Linker | Linker on the lysine side chain | Linker on lysine 20 | γ-glutamic acid and OEG |
| C-terminus | Amide | Amide | Not stated in our sources |
| Molecular formula | C221H342N46O68 | C225H348N48O68 | C187H291N45O59 |
| Molar mass | about 4,731 g/mol | about 4,813 g/mol | about 4,114 g/mol |
| CAS number | 2381089-83-2 | 2023788-19-2 | 910463-68-2 |
Where to find the sequences
Retatrutide and Tirzepatide are both built on human GIP and are both 39 amino acids long. Semaglutide is built on human GLP-1(7–37) and is 31 amino acids long, with two substitutions in the chain: Aib at position 8 and arginine at position 34. The full one-letter sequences are held on the NCATS GSRS and PubChem records and in the structure entries PDB 7FIM and 7KI0; we do not retype them here, so that the sequence you read is the registry's.
Single, dual and triple agonists
An agonist that binds one receptor is a single agonist, two a dual agonist and three a triple agonist. Semaglutide is the single agonist, Tirzepatide the dual (GIP and GLP-1) and Retatrutide the triple (GIP, GLP-1 and glucagon). Tirzepatide was first described by Coskun and colleagues in Molecular Metabolism in 2018 (doi:10.1016/j.molmet.2018.09.009), Semaglutide by Lau and colleagues in the Journal of Medicinal Chemistry in 2015 (doi:10.1021/acs.jmedchem.5b00726), and Retatrutide by Coskun and colleagues in Cell Metabolism in 2022 (doi:10.1016/j.cmet.2022.07.013). Retatrutide's TRIUMPH programme and Tirzepatide's SURPASS programme are registered on ClinicalTrials.gov; we name them and quote no outcome figures. Our guide what is Retatrutide goes further on the first of the three.
What the fatty diacid does in the structure
All three have a fatty diacid joined to a lysine side chain: C20 on Retatrutide and Tirzepatide, C18 on Semaglutide. In Semaglutide it is joined through a γ-glutamic acid and OEG linker, and our sources record that this makes the molecule bind serum albumin. Read the papers above for the same question on the other two.
Cagrilintide: an amylin analogue
Cagrilintide is an amylin analogue, studied alongside Semaglutide. It is not one of the three compared here, and it is a different receptor family. We supply Cagrilintide 10mg as lyophilised powder.
How each is supplied in the UK
Some UK shops sell these compounds as vials of lyophilised powder. R3vive supplies two of them in pre-filled 3 ml pens and one as powder:
| Product | Pack | mg per ml | Price | Price per mg |
|---|---|---|---|---|
| Retatrutide 40mg | Pre-filled 3 ml pen | 13.3 mg/ml | £128.00 | £3.20/mg |
| Tirzepatide 60mg | Pre-filled 3 ml pen | 20 mg/ml | £128.00 | £2.13/mg |
| Semaglutide 10mg | Lyophilised powder | Not applicable | £100.00 | £10.00/mg |
The three sit together on our GLP-1 research peptides page. For the difference between a pen and a vial, read peptide pen vs vial.
Sources
- As in the guide on what Retatrutide is: NCATS GSRS UNII NOP2Y096GV (parent); Coskun et al., Cell Metabolism, 2022; Li et al., Cell Discovery, 2024 (PMC11255275).
- Coskun et al., Molecular Metabolism, 2018, doi:10.1016/j.molmet.2018.09.009; PubChem (tirzepatide); ClinicalTrials.gov (SURPASS).
- Lau et al., Journal of Medicinal Chemistry, 2015, doi:10.1021/acs.jmedchem.5b00726; PubChem CID 56843331.
- PDB 7FIM and 7KI0.
Products in this guide
All products are supplied for research purposes only.