Retatrutide, Tirzepatide and Semaglutide Compared

Scope of this reference

This page compares three separate molecules on documentary questions: what each is, which receptors each was designed for, who developed it, and what kind of evidence exists. It is not a treatment guide, a recommendation, a ranking or a suggestion that any research material is an alternative to a licensed medicine.

What each compound is

Retatrutide (development code LY3437943) is an investigational peptide designed to activate three receptors: the GIP, GLP-1 and glucagon receptors. Eli Lilly developed it. We have found no marketing authorisation for it from the MHRA, the FDA or any other regulator. The catalogue lists it as retatrutide 10mg, 20mg and 30mg lyophilised vials.

Tirzepatide (development code LY3298176) is a 39-residue peptide built on the sequence of GIP and carrying a C20 fatty diacid chain. It was designed to act at two receptors, GIP and GLP-1. Eli Lilly developed it, and it is the active ingredient of a medicine licensed in the UK. Its own page is tirzepatide: identity, development status and evidence.

Semaglutide is a 31-residue analogue of human GLP-1 carrying a C18 fatty diacid chain. It acts at the GLP-1 receptor alone. Novo Nordisk developed it, and it is the active ingredient of several licensed UK medicines.

Where they differ

Two of the three are names of licensed medicines. This page compares molecular design and published records only, and says nothing about the clinical use of either medicine. The receptor pharmacology of retatrutide is set out on the retatrutide mechanism page, and the narrower tirzepatide and semaglutide contrast is on tirzepatide vs semaglutide.

Where the comparison breaks down

The evidence tiers are not comparable. The two licensed molecules have large published trial programmes and years of regulatory and post-marketing record. Retatrutide's record is shorter, has reached phase 3 and not beyond, was funded entirely by its developer, and has produced no marketing authorisation we can find. A table that sets the three side by side is comparing records of different maturity.

No direct trial exists. A PubMed search on 28 October 2026 found no randomised trial that compares retatrutide with tirzepatide or with semaglutide. Statements that rank retatrutide above or below either one are therefore not supported by a head-to-head study. The only direct trials we are aware of compare the two licensed medicines with each other.

Receptor count is a design description, not a performance measure. Activating three receptors is a different design from activating one. Nothing in the design says which is better for any purpose, and the contribution of each receptor in people cannot be separated by studying a single triple agonist.

Trial results for a medicine do not transfer to a research material. A trial describes a clinical formulation, made to clinical standards, given under a protocol to selected patients with medical supervision. A laboratory vial of the same molecule has no such record. Its identity and purity are established by its own batch certificate, and nothing else.

Common conflations

• •"Reta versus tirz" as a like-for-like pair. One is investigational and the other is a licensed medicine. They are not interchangeable categories, and the comparison is of molecules, not products.
• •Brand names as molecule names. Mounjaro is tirzepatide. Ozempic, Wegovy and Rybelsus are semaglutide. Retatrutide has no brand name because it has no licensed product.
• •"More receptors, so stronger." The phrase assumes a common scale. The molecules are different designs and no published head-to-head study supplies one.
• •Compounded and pharmacy-made products. These are products made under other countries' pharmacy rules. They are not the catalogue items described here.
• •Pens. Listings elsewhere that describe pre-filled pens are describing a different product. The catalogue item is a lyophilised powder in a vial.

Reading each record by tier

• •In vitro. The developer's assays describe activity at each receptor for retatrutide and tirzepatide. Retatrutide showed balanced glucagon and GLP-1 receptor activity with greater GIP receptor activity. Tirzepatide's published profile is close to native GIP at its GIP receptor and lower than native GLP-1 at the GLP-1 receptor. Both profiles are developer-reported.
• •Animal. The retatrutide founding paper reports work in obese mice. Rodent findings establish behaviour in that species only.
• •Human. Published trials exist for all three, and each describes its own product. They are the only tier where claims about people could be grounded, and they apply only to the clinical formulation studied. The retatrutide trials are summarised on the retatrutide research review.

Analytical documentation

A certificate of analysis reports the identity and measured purity of the particular batch tested. It does not establish a biological or therapeutic outcome, and it does not extend to other batches. The retatrutide batches are 100234 (10mg, HPLC 99.682%), 100235 (20mg, 99.516%) and 100236 (30mg, 99.831%), and their reports are in the COA library. The guides to reading a peptide COA and understanding HPLC purity explain the limits. The retatrutide identity page and buying guide cover the rest of the catalogue side, and GLP-1 peptides versus classic research peptides explains why this class rests on a different evidence base.

Key references

• •Coskun T, Urva S, Roell WC, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and [...]: from discovery to clinical proof of concept. Cell Metab. 2022;34(9):1234-1247. doi:10.1016/j.cmet.2022.07.013
• •Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-hormone-receptor agonist retatrutide for obesity: a phase 2 trial. N Engl J Med. 2023;389(6):514-526. doi:10.1056/NEJMoa2301972
• •Jastreboff AM, Kaplan LM, Davies MJ, et al. Retatrutide, a triple hormone receptor agonist, for treatment of obesity (TRIUMPH-1). N Engl J Med. 2026. doi:10.1056/NEJMoa2604169

Laboratory-use boundary

Materials sold on this site are supplied solely for non-clinical in-vitro laboratory research. They must not be ingested, injected, inhaled, applied or otherwise administered to a human or animal.

We do not provide dosing, routes of administration, treatment guidance, cosmetic-use guidance or in-vivo protocols. Preparation, storage and handling must follow a validated institutional SOP, the material documentation and an appropriate risk assessment.