The core distinction across the incretin class is how many receptors each compound engages: semaglutide is a single GLP-1 receptor agonist, tirzepatide is a dual GIP/GLP-1 agonist, and retatrutide (LY3437943) is a triple GIP/GLP-1/glucagon agonist. This page compares them by receptor target, structural class, half-life, and development stage. It is a pharmacological and structural comparison for research context — it does not compare human clinical outcomes or make suitability claims, and retatrutide is investigational and not approved for use.
Master comparison table
| Semaglutide | Tirzepatide | Retatrutide (LY3437943) | |
|---|---|---|---|
| Receptor targets | GLP-1R | GIP/GLP-1R | GIP/GLP-1/GCGR |
| Class | Mono-agonist | Dual agonist | Triple agonist |
| Developer | Novo Nordisk | Eli Lilly | Eli Lilly |
| Distinguishing arm | — (reference GLP-1) | Adds GIP | Adds GIP and glucagon |
| Half-life extension | Fatty-acid acylation | Fatty-acid acylation | C20 fatty-diacid, albumin binding |
| Dosing cadence (clinical) | Once weekly | Once weekly | Once weekly (trials) |
| Development stage | Approved | Approved | Investigational — Phase 3 ongoing |
Reading the table
Semaglutide is the reference GLP-1 mono-agonist and the simplest pharmacology of the three — a useful baseline for any comparison.
Tirzepatide adds GIP-receptor agonism to the GLP-1 arm, making it the first widely studied dual incretin agonist. The addition of the GIP axis is the whole story of what separates it from semaglutide.
Retatrutide adds a third arm — glucagon-receptor agonism — on top of the GIP/GLP-1 dual base. It is the most receptor-complex of the three and the only one still investigational. The glucagon arm is the defining and most-studied point of difference; see the mechanism-of-action page on retatrutide’s receptor pharmacology for why glucagon agonism is added despite its classical glucose-raising role.
Other compounds in the class
The class is broader than these three. Survodutide and mazdutide are GLP-1/glucagon dual agonists; efocipegtrutide (HM15211) is another triple GLP-1/GIP/glucagon agonist in earlier development. Naming these makes the comparison comprehensive rather than cherry-picked.
Handling and stability differences (research context)
For a laboratory, the practical differences matter as much as the receptor profile: reconstitution behaviour, storage stability across temperatures, and lot-to-lot purity considerations for research-grade material. As with all peptides in this class, RETApro’s retatrutide is supplied lyophilised, cold-chain shipped, and stored at 2–8 °C away from light; each lot ships with an independently verifiable Certificate of Analysis reporting HPLC purity and mass-spectrometry identity. Handling notes here concern research material only and carry no human-use framing.
For how to assess that handling and quality in any supplier, see our due-diligence guide to evaluating a research peptide supplier.
Regulatory status
Semaglutide and tirzepatide are approved medicines. Retatrutide is not approved by any regulator; it is an investigational compound supplied for laboratory research use only. Any clinical figures referenced elsewhere on the site are published trial findings, not statements of availability or efficacy for use.
Frequently asked questions
What is the difference between retatrutide and tirzepatide?
Both are Eli Lilly incretin agonists, but they engage a different number of receptors. Tirzepatide is a dual agonist of the GIP and GLP-1 receptors. Retatrutide adds a third target — the glucagon receptor — making it a triple GIP/GLP-1/glucagon agonist. Tirzepatide is an approved medicine; retatrutide is investigational and not approved. This is a pharmacological distinction, not a comparison of human outcomes.
What is the difference between retatrutide and semaglutide?
Semaglutide is a single GLP-1 receptor agonist — the simplest pharmacology of the three and the reference point for the class. Retatrutide engages three receptors (GIP, GLP-1, and glucagon) rather than one. Semaglutide is approved; retatrutide is an investigational compound supplied for laboratory research use only.
Is retatrutide better than tirzepatide or semaglutide?
This page does not make suitability or "which is better" claims. Semaglutide and tirzepatide are approved medicines; retatrutide is investigational and not approved for use. Any clinical trial figures reported elsewhere on this site are published findings for research context, not statements of comparative efficacy for use.
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