Semaglutide vs Tirzepatide vs Retatrutide
Semaglutide, tirzepatide and retatrutide form a graded series in receptor coverage that is useful for laboratory research on incretin and glucagon receptor signaling. Semaglutide activates one receptor (GLP-1), tirzepatide activates two (GIP and GLP-1), and retatrutide activates three (GIP, GLP-1 and the glucagon receptor, GCGR). All three are lipidated peptides that bind serum albumin, with reported half-lives between about 5 and 7 days, so receptor coverage can be compared with relatively few differences in pharmacokinetic profile.
Because receptor coverage is the main variable, the three are often studied as a set: semaglutide as the GLP-1 receptor reference, tirzepatide to add GIP receptor activity, and retatrutide to add glucagon receptor activity on top of both. This page compares their structure, receptor pharmacology and laboratory handling, drawing only on published molecular and pharmacological data.
In this catalog the three compounds are listed as GLP-1 SM (semaglutide), GLP-2 TZ (tirzepatide) and GLP-3 RT (retatrutide). All are supplied as lyophilized powder strictly for in-vitro laboratory research and are not for human or animal consumption.
| Property | Semaglutide | Tirzepatide | Retatrutide |
|---|---|---|---|
| Receptor targets | GLP-1 receptor only | GIP receptor and GLP-1 receptor | GIP, GLP-1 and glucagon (GCGR) receptors |
| Class | Selective GLP-1 receptor mono-agonist | Dual GIP/GLP-1 receptor agonist, described as "imbalanced" | Single-peptide triple receptor agonist |
| Peptide basis | Human GLP-1(7-37), about 94% sequence identity; Aib at position 8; Lys34Arg substitution | GIP sequence; Aib at positions 2 and 13; C-terminal amide | Engineered single peptide with activity at all three receptors |
| Length | Same length as native GLP-1(7-37) | 39 amino acids, linear | 39 amino acids |
| Fatty-acid moiety | C18 fatty diacid on Lys26 through a gamma-glutamic acid / OEG linker (albumin binding) | C20 fatty diacid through a linker (albumin binding) | C20 fatty diacid (albumin binding) |
| Molecular formula | C187H291N45O59 | C225H348N48O68 | C221H342N46O68 |
| Molecular weight | About 4113.6 Da | About 4813.5 Da | About 4731.4 Da |
| Half-life (pharmacokinetic property) | About 7 days (roughly 165 hours) | About 5 days | About 6 days |
| Supplied form in this store | GLP-1 SM: lyophilized powder, 10mg vial | GLP-2 TZ: lyophilized powder, 10mg and 20mg vials | GLP-3 RT: lyophilized powder, 10mg and 20mg vials |
About Semaglutide
Semaglutide is the single-receptor reference point of the three. Its backbone is based on human GLP-1(7-37), with about 94% sequence identity to the native hormone, an Aib substitution at position 8 for DPP-4 resistance and a Lys34Arg substitution. The remaining lysine, Lys26, carries a C18 fatty diacid through a gamma-glutamic acid / OEG linker that binds serum albumin. That design gives semaglutide the longest reported half-life of the three, about 7 days (roughly 165 hours) in published pharmacokinetic data, and a molecular weight of about 4113.6 Da.
In cell and animal models semaglutide has been used to study glucose-dependent insulin secretion, gastric emptying and appetite-related signaling pathways that follow from GLP-1 receptor activation alone. It has been studied extensively in published literature, including clinical research (see a PubMed search for semaglutide). The semaglutide research overview covers its pharmacology in more detail, and the semaglutide reconstitution guide covers 10mg vial preparation.
About Tirzepatide
Tirzepatide adds GIP receptor activity. It is a 39-amino-acid linear peptide built on the GIP sequence, with Aib at positions 2 and 13, an amidated C-terminus and a C20 fatty diacid moiety attached through a linker for albumin binding; its reported half-life is about 5 days. It is described as an "imbalanced" agonist, with GIP receptor affinity comparable to native GIP and GLP-1 receptor affinity weaker than native GLP-1. At the GLP-1 receptor it favors cAMP signaling over beta-arrestin recruitment, a form of biased agonism.
In cell and animal models tirzepatide has been used to study incretin signaling and the interplay between GIP and GLP-1 receptor pathways. It has been studied extensively in published literature, including clinical research (see a PubMed search for tirzepatide). See the tirzepatide research overview and the tirzepatide reconstitution guide for 10mg and 20mg vials.
About Retatrutide
Retatrutide adds glucagon receptor activity on top of the incretin pair. It is a single 39-amino-acid peptide that activates the GIP, GLP-1 and glucagon (GCGR) receptors, carries a C20 fatty diacid moiety for albumin binding and has a reported half-life of about 6 days. It is reported to be more potent than native GIP at the GIP receptor and less potent than the native ligands at the GLP-1 and glucagon receptors.
Glucagon receptor signaling is linked in cell and animal models to energy expenditure and hepatic metabolism, which is why retatrutide appears in studies that bring those pathways into the same experiment as incretin signaling. Its published literature, which includes clinical research, is the smallest of the three (see a PubMed search for retatrutide). See the retatrutide research overview and the retatrutide reconstitution guide for 10mg and 20mg vials.
Which Should Researchers Choose?
- GLP-1 receptor signaling in isolation: semaglutide acts at one receptor, so it is the reference when effects must be attributed to GLP-1 receptor activation alone.
- What GIP receptor activity adds: comparing tirzepatide with semaglutide isolates the contribution of GIP receptor engagement.
- What glucagon receptor activity adds: comparing retatrutide with tirzepatide, two 39-amino-acid peptides with C20 fatty diacid moieties, isolates the glucagon receptor contribution.
- Graded receptor coverage: running all three in parallel gives a one-, two- and three-receptor series for concentration-response and signaling experiments.
- GLP-1 receptor signaling bias: tirzepatide's cAMP-favoring profile can be contrasted with semaglutide in cAMP accumulation and beta-arrestin recruitment assays.
- Energy expenditure and hepatic metabolism models: retatrutide is the relevant compound when glucagon receptor-linked pathways are part of the hypothesis.
For two-compound detail, see semaglutide vs tirzepatide, tirzepatide vs retatrutide and semaglutide vs retatrutide.
Frequently Asked Questions
What is the main difference between semaglutide, tirzepatide and retatrutide?
The number of receptors each activates. Semaglutide acts at the GLP-1 receptor only, tirzepatide at the GIP and GLP-1 receptors, and retatrutide at the GIP, GLP-1 and glucagon receptors. All three are lipidated peptides that bind serum albumin.
Why study all three together?
They form a series in which receptor coverage changes while albumin binding and half-life stay broadly comparable, so each added receptor can be examined against the compound that lacks it. Relative potency still differs at each receptor, which is why matched concentration-response data for every compound are part of a sound design.
Which has the longest half-life?
Semaglutide, at about 7 days (roughly 165 hours) in published pharmacokinetic data, followed by retatrutide at about 6 days and tirzepatide at about 5 days. In each case the extended half-life reflects albumin binding by the fatty diacid moiety, a property of the molecule itself.
How are the lyophilized vials stored and reconstituted?
All three are handled the same way. Lyophilized vials are stored cold at 2-8 °C, or at -20 °C for long-term storage, and protected from light. They are reconstituted with bacteriostatic water (0.9% benzyl alcohol in sterile water). The reconstituted solution is kept refrigerated at 2-8 °C, is not shaken, and is not frozen and thawed repeatedly. The reconstitution guides linked above cover each product.
Are these approved for human use?
No. The research-grade semaglutide, tirzepatide and retatrutide sold here are not approved for human use and are not for human or animal consumption. They are supplied strictly for in-vitro laboratory research, they are not medicines, and they are not equivalent to any approved pharmaceutical product.
How are these listed in the catalog?
In this catalog, GLP-1 SM is semaglutide (10mg vial), GLP-2 TZ is tirzepatide (10mg and 20mg vials) and GLP-3 RT is retatrutide (10mg and 20mg vials). Bacteriostatic water is sold separately in 3 mL and 10 mL vials. Each batch is verified by HPLC and mass spectrometry, with its Certificate of Analysis published on the COA page.
Shop these products
- Ships the same business day
- Free US shipping on $199+
- 14-day money-back guarantee