Last reviewed: October 2026 · Cleared Peptides research team
Retatrutide, tirzepatide and semaglutide are three acylated peptides that represent successive steps in incretin-receptor ligand design: single-, dual- and triple-receptor agonism. This page compares them side by side using published structural and in-vitro data.
Side-by-Side Comparison
| Semaglutide | Tirzepatide | Retatrutide | |
|---|---|---|---|
| Code | NN9535 | LY3298176 | LY3437943 |
| CAS | 910463-68-2 | 2023788-19-2 | 2381089-83-2 |
| Formula | C187H291N45O59 | C225H348N48O68 | C221H342N46O68 |
| MW (g/mol) | ≈4113.6 | ≈4813.5 | ≈4731.3 |
| Length | 31 aa | 39 aa | 39 aa |
| Template sequence | GLP-1(7–37) | GIP-based | GIP-based |
| Receptors (in vitro) | GLP-1R | GIPR + GLP-1R | GIPR + GLP-1R + GCGR |
| Fatty acid | C18 diacid | C20 diacid | C20 diacid |
| Research product | CP-SEMA | CP-T | CP-Reta |
Receptor Targets: One, Two or Three
Semaglutide is selective for the GLP-1 receptor. Tirzepatide adds GIP-receptor agonism and is reported to be GIPR-biased. Retatrutide additionally activates the glucagon receptor. In research, these three compounds form a natural series for dissecting the contribution of each receptor to downstream signaling.
Structural Differences
All three use protease-resistant Aib residues and a fatty-diacid side chain for albumin binding. Semaglutide is built on the GLP-1 sequence with a C18 diacid; tirzepatide and retatrutide are built on GIP-derived sequences with C20 diacids, and retatrutide includes additional α-methylated residues.
Which Compound Fits Which Experiment?
- GLP-1R-only reference: semaglutide
- GIPR/GLP-1R co-agonism and biased-signaling studies: tirzepatide
- Glucagon-receptor contribution / tri-agonism: retatrutide (or UBT-251)
- Amylin + GLP-1 combination: cagrilintide + semaglutide
Detailed guides: retatrutide · tirzepatide · semaglutide.
Research materials referenced in this guide
Frequently Asked Questions
What is the difference between retatrutide and tirzepatide?
Tirzepatide is a dual GIPR/GLP-1R agonist; retatrutide also activates the glucagon receptor, making it a triple agonist.
What is the difference between tirzepatide and semaglutide?
Semaglutide acts only at GLP-1R and is built on the GLP-1 sequence; tirzepatide is GIP-based and acts at both GIPR and GLP-1R.
Are all three tested for purity?
Yes. Every Cleared Peptides lot of CP-Reta, CP-T and CP-SEMA is independently tested by HPLC and MS, with COAs on our COA page.
Selected References
Peer-reviewed literature on the compounds discussed in this guide, listed as scientific background for laboratory researchers. Citation does not imply endorsement by the authors or any use other than in-vitro research.
- Li W, et al. Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide. Cell Discov. 2024;10(1):77. PubMed 39019866 · DOI
- Willard FS, et al. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight. 2020;5(17). PubMed 32730231 · DOI
- Lau J, et al. Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J Med Chem. 2015;58(18):7370-80. PubMed 26308095 · DOI
- Knudsen LB, et al. The Discovery and Development of Liraglutide and Semaglutide. Front Endocrinol (Lausanne). 2019;10:155. PubMed 31031702 · DOI
Laboratory note: solubility depends on salt form and solvent. This guide does not state a single solubility figure. Handling of lyophilized material is described in the peptide storage guide.
Research Use Only Notice
This guide is provided for educational and laboratory reference purposes. It summarizes published, primarily in-vitro and structural research literature and does not describe, recommend or imply any use in humans or animals. Products sold by Cleared Peptides are for laboratory research use only; they are not drugs, foods, cosmetics or dietary supplements, are not FDA-approved, and are not intended to diagnose, treat, cure, mitigate or prevent any disease. No dosing, administration or therapeutic information is provided.
