Semaglutide, tirzepatide and retatrutide are synthetic peptides that bind to the receptors of hormones produced by the gut and the pancreas. They differ in the number of receptors they act on: semaglutide is a GLP-1 receptor agonist, tirzepatide acts on the GIP and GLP-1 receptors, and retatrutide on the GIP, GLP-1 and glucagon receptors. Semaglutide and tirzepatide are also authorised by the European Medicines Agency (EMA) as prescription medicines, whereas retatrutide is an investigational molecule with no marketing authorisation.
Retatrutide is not a medicine and not an alternative to prescribed medicines; it is intended exclusively for laboratory research. This article compares the three substances in terms of receptors, structure and regulatory status. It does not cover effects, study outcomes or use.
The three substances at a glance
| Feature | Semaglutide | Tirzepatide | Retatrutide |
|---|---|---|---|
| Developer | Novo Nordisk | Eli Lilly | Eli Lilly |
| Research code | – | LY3298176 | LY3437943 |
| Receptors | GLP-1 | GIP and GLP-1 | GIP, GLP-1 and glucagon |
| Type of agonist | single | dual | triple |
| Structure | analogue of human GLP-1 with a fatty acid chain | 39-amino-acid peptide with a C20 fatty acid | 39-amino-acid peptide based on GIP, with a C20 fatty acid |
| Status in the EU | authorised (Ozempic 2018, Rybelsus 2020, Wegovy 2022) | authorised (Mounjaro 2022) | no marketing authorisation; phase 3 (TRIUMPH) |
| Status in the US | approved by the FDA | approved by the FDA | not approved |
The years refer to the European marketing authorisation, as stated in the EMA’s EPARs [4].
What ‘triple agonist’ means at receptor level
GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) are hormones that the gut releases after a meal. Glucagon is a hormone produced by the pancreas. Each of these hormones has its own receptor on the cell surface. An agonist is a molecule that binds to such a receptor and activates it, just as the body’s own hormone does.
- A single agonist, such as semaglutide, activates one receptor: the GLP-1 receptor.
- A dual agonist, such as tirzepatide, activates both the GIP and the GLP-1 receptor with a single molecule [2].
- A triple agonist, such as retatrutide, activates the GIP, GLP-1 and glucagon receptors with a single molecule [1].
A triple agonist is therefore not a mixture of three substances but a single peptide chain, designed to be recognised by three different receptors. Its activity is not necessarily spread evenly either: in laboratory tests (in vitro), retatrutide’s activity at the glucagon and GLP-1 receptors was roughly balanced, and higher at the GIP receptor [1]. Acting on more receptors gives a different pharmacological profile; it does not automatically make a substance ‘stronger’.
Structure: three peptides with a fatty acid chain
All three are derived from natural hormones and have been chemically modified. Two modifications recur: non-coded amino acids, and a fatty acid chain that binds temporarily to albumin in the blood, which extends the half-life.
- Semaglutide is an analogue of human GLP-1. A fatty acid that binds reversibly to albumin is attached via a linker [3].
- Tirzepatide is a linear peptide of 39 amino acids with two non-coded amino acids (Aib, α-aminoisobutyric acid, at positions 2 and 13). A C20 fatty acid is attached via a linker to the lysine at position 20 [2].
- Retatrutide is a 39-amino-acid peptide derived from the GIP sequence. It contains three non-coded amino acids: Aib at positions 2 and 20, and α-methyl-leucine at position 13. A C20 fatty acid is attached via a linker to the lysine at position 17 [1].
This structure matters for analysis: the expected mass is calculated from the complete structure, including the non-coded amino acids, the linker and the fatty acid, and a mass spectrometry measurement should match it.
Development and regulatory status
Semaglutide was developed by Novo Nordisk. In the EU it is authorised as Ozempic (since 8 February 2018), as Rybelsus in tablet form (since 3 April 2020) and as Wegovy (since 6 January 2022) [4].
Tirzepatide was developed by Eli Lilly and has been authorised in the EU as Mounjaro since 15 September 2022 [4].
Retatrutide is also an Eli Lilly molecule. Following phase 1 and phase 2 studies, the phase 3 TRIUMPH programme is now under way. According to ClinicalTrials.gov, TRIUMPH-1 (NCT05929066), TRIUMPH-2 (NCT05929079), TRIUMPH-3 (NCT05882045) and TRIUMPH-4 (NCT05931367) have been completed. A longer-running phase 3 study (NCT06383390) is still ongoing. In July 2026, Eli Lilly announced plans to submit an application for approval to the FDA in the first quarter of 2027 [5]. The company itself describes retatrutide as an investigational molecule that may not be sold or promoted for human use [5].
As of 30 September 2026, retatrutide therefore has no marketing authorisation in the EU or the US.
What this means for research material
Clean Peptides retatrutide is research material (research use only), not a medicine. Because there is no approved reference product, the things that matter most are the analysis, the batch and the storage.
- Identity and purity. HPLC determines the purity; mass spectrometry confirms whether the correct molecule is present. For how to read this data, see How to read a certificate of analysis (COA).
- Batch number. Every vial and pen has a batch number on its label. Record it with every experiment, so that results can always be traced back to a specific batch.
- Form. Retatrutide is available as lyophilised powder in a vial and as a solution in a pre-filled pen. The differences are explained in Retatrutide pen or vial.
- Storage. Temperature, light and moisture determine how stable the material remains; see How to store retatrutide.
Clinical studies of these substances are carried out under medical supervision with product manufactured to pharmaceutical standards; they say nothing about products for laboratory research. If you have any questions about your health, please consult your doctor. Clean Peptides does not supply medicines.
Products and further reading
Products
Retatrutide as a pre-filled pen: retatrutide pen 15 mg, 20 mg, 30 mg and 40 mg. As a vial of lyophilised powder: retatrutide 15 mg, 20 mg, 30 mg and 40 mg. All strengths and prices are listed on the retatrutide overview page.
Further reading
- Retatrutide: overview and strengths
- Retatrutide pen or vial: what are the differences?
- Purity, endotoxins and heavy metals in peptides
- Research use only (RUO): what does it mean?
Sources
- Coskun T, Urva S, Roell WC, et al. 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 Metabolism 2022;34(9):1234–1247.e9. doi:10.1016/j.cmet.2022.07.013
- Coskun T, Sloop KW, Loghin C, et al. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Molecular Metabolism 2018;18:3–14. doi:10.1016/j.molmet.2018.09.009
- Knudsen LB, Lau J. The Discovery and Development of Liraglutide and Semaglutide. Frontiers in Endocrinology 2019;10:155. doi:10.3389/fendo.2019.00155
- European Medicines Agency. EPARs for Ozempic, Rybelsus, Wegovy and Mounjaro (accessed 30 September 2026)
- Eli Lilly and Company. Press release on the TRIUMPH programme, 23 July 2026. prnewswire.com (accessed 30 September 2026)
For laboratory research only. Clean Peptides products are not intended for use in humans or animals. This article provides general information and is not medical advice.
