Semaglutide, tirzepatide, retatrutide: one, two and three receptors

Three names dominate the search results for this class, and most comparison pages line them up by a single number borrowed from three different trials. That isn't a comparison. This is the one that can be made honestly: what each molecule is, what it binds, who made it, what's licensed, and what's been published.

At a glance

The receptors

GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) are the two incretin hormones, released from the gut after food and acting on the pancreas and on appetite circuits in the brain. Glucagon is the pancreatic hormone that raises glucose output from the liver and increases energy expenditure.

• Semaglutide is an analogue of GLP-1 itself: same hormone, modified for stability and a long half-life.
• Tirzepatide starts from GIP and is engineered so the same peptide also activates the GLP-1 receptor — a "dual agonist".
• Retatrutide starts from GIP and is engineered to activate all three — a "triple agonist". In cell assays its potency is deliberately unbalanced across the three, a design choice discussed in the discovery paper.

That ordering — one, two, three — is why the compounds are so often presented as a progression. Whether more receptors is better for any purpose is precisely the question the trial programmes exist to answer, and not one this page will pre-empt.

The chemistry

All three are synthetic peptides carrying a fatty-acid chain that binds albumin in the blood, which is what turns a hormone with a half-life of minutes into a molecule that lasts days. Semaglutide is the shortest and lightest, being a modified copy of a 31-residue natural hormone. Tirzepatide and retatrutide are near-siblings: both 39 residues on a GIP backbone, within a hundred daltons of each other, distinguishable on an HPLC-MS certificate by observed mass rather than by retention time. How to read that field.

What's licensed, and what isn't

This is the distinction that matters most and gets blurred most.

Semaglutide is a licensed medicine in the UK in several forms — Ozempic, Wegovy, Rybelsus, and an oral Wegovy formulation — available on prescription and, for some indications, on the NHS.

Tirzepatide is a licensed medicine in the UK as Mounjaro, on prescription, with NHS availability being phased in. Research-grade tirzepatide is the same molecule and is not that product. What "research grade" means.

Retatrutide is licensed nowhere. It is in phase 3 trials and cannot be prescribed. The UK legal position in full.

Where to read the evidence

• Semaglutide: the SUSTAIN and PIONEER programmes (type 2 diabetes), STEP (obesity) and OASIS (oral, obesity), published mainly in the New England Journal of Medicine and The Lancet from 2016 onward.
• Tirzepatide: SURPASS (type 2 diabetes) and SURMOUNT (obesity), 2021–2023, including SURPASS-2, which compared tirzepatide with semaglutide directly — the only published head-to-head among these three.
• Retatrutide: phase 2 in obesity (Jastreboff et al., NEJM, 2023) and in type 2 diabetes (Rosenstock et al., The Lancet, 2023); phase 3 ongoing.

We link the headline papers below rather than quoting figures from them. Numbers from one trial placed next to numbers from another — different populations, durations and designs — are not a comparison, and a site that sells two of the three compounds is the wrong place to be presenting them as one.

For a research buyer

Tirzepatide and retatrutide are handled identically in supply: pre-filled pen, 2–8°C, manufacturer certificate per batch with an independent Janoshik report as each completes, all on the testing page. The full side-by-side of those two covers the details. Biovanta does not supply semaglutide; it is available as a licensed medicine through a prescriber. Everything supplied is for in-vitro laboratory research only.