Incretin Research Compounds
Tirzepatide vs Retatrutide: Two Receptors Against Three, and One Label Against None
Most comparisons of these two are written as though they sit at the same stage of evidence. They do not. Tirzepatide has an FDA-approved label a regulator reviewed; retatrutide has none, is still called investigational by its own sponsor, and everything known about it comes from trial reports that sponsor wrote. That asymmetry, and the extra receptor behind it, is the comparison. Research-use education only.
The short answer
Tirzepatide is a dual GIP/GLP-1 receptor agonist with an approved label. Retatrutide is a triple GIP/GLP-1/glucagon receptor agonist with none. The tirzepatide labeling states what the molecule is: based on the GIP sequence, with aminoisobutyric acid at positions 2 and 13, a C-terminal amide, and a lysine at position 20 attached to 1,20-eicosanedioic acid via a linker — a C20 fatty diacid the same labeling says enables albumin binding and prolongs the half-life. Retatrutide adds glucagon-receptor agonism, and no approved label describes it: a label is a description a regulator committed to, a trial report one written by the party that ran the trial.
What each molecule actually is
Tirzepatide is settled, though not by PubChem. Formula C225H348N48O68, molecular weight 4813.53 Da, FDA unique ingredient identifier OYN3CCI6QE — the first two printed in the approved label rather than computed from a deposit, which is what makes them checkable. PubChem is the weaker source even here: a compound-name query returns five CIDs, none carrying a title, and the record PubChem does title “Tirzepatide” (CID 156588324) lists “Zepbound” and “tirzepatide sodium salt” among its synonyms — a salt deposit, not the labeled substance.
Retatrutide has no such anchor. A PubChem compound-name query returns nothing, so does its development code LY3437943, and the autocomplete does not carry the word at all. The name reaches PubChem only through supplier deposits — CID 171934787, “Retatrutide (sodium salt)”, and a series titled “Retatrutide Impurity”. Those agree on C221H342N46O68, an average molecular weight near 4731 Da and an exact mass of 4730.48: usable, but a depositor consensus rather than a figure a regulator signed off on. This page prints no sequence for either compound; retatrutide’s was not resolvable at a source checkable character by character.
The third receptor, and what it is thought to do
GIP and GLP-1 are incretin receptors; the glucagon receptor is not, so adding it is not more of the same thing. The discovery paper — Coskun and colleagues, Cell Metabolism, September 2022 — reports that in obese mice the glucagon-receptor component contributed by increasing energy expenditure, on top of the calorie-intake reduction driven through GIP and GLP-1: the third receptor acts on the other side of the energy balance. The same paper reports that in vitro the molecule shows balanced glucagon- and GLP-1-receptor activity but more GIP-receptor activity. Whether any of that produces an advantage in humans is a separate question from whether it happens in a mouse.
Side by side
| Property | Tirzepatide | Retatrutide |
|---|---|---|
| Receptor targets | GIP and GLP-1 — dual agonist | GIP, GLP-1 and glucagon — triple agonist |
| U.S. regulatory status | Approved. Mounjaro, NDA 215866, 13 May 2022; Zepbound, NDA 217806, 8 November 2023 | Investigational. No application in Drugs@FDA; no record in the openFDA label endpoint |
| Molecular formula | C225H348N48O68 | C221H342N46O68 |
| Molecular weight | 4813.53 Da, printed on the approved label | Average 4731 Da, exact mass 4730.48 — computed by PubChem from a deposited structure, not stated by any regulator |
| FDA UNII | OYN3CCI6QE | Not carried in the FDA label database |
| PubChem name lookup | Returns five CIDs, none of them titled; the record titled Tirzepatide (CID 156588324) is a salt deposit | Returns nothing. The compound name index has no entry at all |
| ChEMBL development phase | Max phase 4 (CHEMBL4297839) | Max phase 3 (CHEMBL5095485) |
| Largest trial with posted results | SURPASS-CVOT, NCT04255433, 13,299 participants | The Phase 2 obesity trial, NCT04881760, 338 participants |
| Marketed presentation | Ready-to-use solution: single-dose pens and vials, plus preserved multi-dose vials and pens | No approved presentation. U.S. drug-code entries are bulk drug substance; the DailyMed filings come from an unapproved labeler |
| Research-market vial sizes | Commonly 10, 15 and 30 mg | Commonly 5, 10 and 20 mg |
Sources: approved labeling and Drugs@FDA for regulatory status, PubChem for molecular identity, ChEMBL for development phase, ClinicalTrials.gov for trial records. A side-by-side table is not a head-to-head result.
One has a label. The other has none.
Tirzepatide is approved in the United States under two applications, and the indications below are worded as they stand today rather than as first written. Mounjaro, NDA 215866, approved 13 May 2022: glycemic control in adults and pediatric patients 10 years of age and older with type 2 diabetes. Zepbound, NDA 217806, approved 8 November 2023: reducing excess body weight and maintaining weight reduction long term in adults with obesity or overweight with at least one weight-related comorbid condition, plus — via an efficacy supplement approved 20 December 2024 — moderate to severe obstructive sleep apnea in adults with obesity.
For retatrutide there is no equivalent paragraph, and the searches establishing that are worth naming. Drugs@FDA returns no application with retatrutide as an active ingredient; the openFDA drug-label endpoint returns no record. Its sponsor’s pre-approval expanded-access listing, NCT07629401, calls it an “investigational GLP-1/GIP/glucagon triple receptor agonist” — and expanded access exists only for an unapproved drug. Those are U.S. registers, queried directly; for other jurisdictions this page rests on the sponsor’s own description rather than implying a search it did not run.
Two near-misses look like approvals and are not. DailyMed does return retatrutide records — ten, all from one labeler, a cross-border e-commerce company, several under a brand name appearing nowhere in Drugs@FDA. A Structured Product Label is a document a company filed, not a decision a regulator made. The drug-code directory returns a dozen more, every one in the “bulk ingredient” category: raw-material registrations, not cleared products.
The gap that leaves is not academic: material labeled retatrutide circulates ahead of any approval. In 2026 The BMJ ran a fact check headlined on whether a man had died after taking the unapproved compound (BMJ 2026;394:e100245) and a report that the sponsor had opened compassionate-use access (BMJ 2026;394:e100530). Those are cited as headlines, not findings — the articles were not read for this page.
The tirzepatide trial record
Two named programmes: SURPASS in type 2 diabetes, SURMOUNT in weight management. Every record below is marked completed and carries posted results on ClinicalTrials.gov.
| Trial | Registry ID | Enrolled | What it tested |
|---|---|---|---|
| SURPASS-1 | NCT03954834 | 478 | Monotherapy in type 2 diabetes |
| SURPASS-2 | NCT03987919 | 1,879 | Against semaglutide 1 mg |
| SURPASS-CVOT | NCT04255433 | 13,299 | Against dulaglutide on major cardiovascular events |
| SURMOUNT-1 | NCT04184622 | 2,539 | Obesity, 72 weeks, placebo-controlled |
| SURMOUNT-OSA | NCT05412004 | 469 | Obstructive sleep apnea with obesity |
Two as reported figures. SURMOUNT-1 randomised 2,539 adults without diabetes to weekly tirzepatide at 5, 10 or 15 mg or placebo for 72 weeks, reporting mean weight changes at week 72 of −15.0%, −19.5% and −20.9% against −3.1%. SURPASS-2, against semaglutide 1 mg, reported HbA1c changes of −2.01, −2.24 and −2.30 percentage points against −1.86, concluding non-inferiority and superiority at 40 weeks.
The retatrutide record, and where it thins out
A substantial programme, and a gap between its size and how much of it has been reported.
| Trial | Registry ID | Participants | Reporting status |
|---|---|---|---|
| Phase 2, obesity | NCT04881760 | 338 | Results posted; published in NEJM, 2023 |
| Phase 2, type 2 diabetes | NCT04867785 | 281 | Results posted; published in The Lancet, 2023 |
| TRANSCEND-T2D-1, Phase 3 | NCT06354660 | 537 | Completed; no registry results posted, but published in The Lancet, June 2026 |
| TRIUMPH-1, Phase 3 | NCT05929066 | 2,335 (2,339 randomised in the paper) | Completed; published in NEJM, 29 September 2026; no registry results posted |
| TRIUMPH-2, Phase 3 | NCT05929079 | 1,152 | Completed; published in The Lancet, 29 September 2026; no registry results posted |
| TRIUMPH-3, Phase 3 | NCT05882045 | 1,946 | Completed; no results posted; no primary publication found (3 October 2026) |
| TRIUMPH-4, Phase 3 | NCT05931367 | 445 | Completed; no results posted; no primary publication found (3 October 2026) |
| TRIUMPH-5, Phase 3 | NCT06662383 | 800 est. | Active; head-to-head against tirzepatide |
| Cardiovascular and kidney outcomes | NCT06383390 | 10,000 est. | Active; primary completion listed for 2029 |
What has been published, precisely. The Phase 2 obesity trial (NCT04881760, 338 adults) reported mean weight changes at 48 weeks of −8.7% at 1 mg, −17.1% at 4 mg, −22.8% at 8 mg and −24.2% at 12 mg against −2.1% for placebo, with dose-related gastrointestinal adverse events and dose-dependent heart-rate increases peaking at 24 weeks then declining. The Phase 2 diabetes trial (NCT04867785, 281 adults) reported HbA1c changes at 24 weeks from −0.43% at 0.5 mg to −2.02% at 12 mg, against −0.01% for placebo and −1.41% for its 1.5 mg dulaglutide comparator. The first published Phase 3 result, TRANSCEND-T2D-1 (NCT06354660, 537 adults, Lancet, June 2026), reported HbA1c changes at 40 weeks of −1.69%, −1.86% and −1.94% at 4, 9 and 12 mg against −0.81%, with body-weight changes of −11.5%, −13.9% and −15.3% against −2.6%. Two more Phase 3 trials were published on 29 September 2026. TRIUMPH-1 (NCT05929066, NEJM, 2,339 adults with obesity and no diabetes, 80 weeks) reported body-weight changes of −17.6%, −23.7% and −25.0% at 4, 9 and 12 mg against −3.9% for placebo. TRIUMPH-2 (NCT05929079, Lancet, 1,152 adults with obesity and type 2 diabetes, 80 weeks) reported −11.9%, −16.8% and −18.8% against −5.1%, with more diarrhoea, nausea, low blood pressure and dysesthesia on retatrutide than on placebo.
Now what is still missing. Two of the four pivotal obesity trials have reported; two have not. TRIUMPH-1 and TRIUMPH-2 were published on 29 September 2026. TRIUMPH-3 (NCT05882045, 1,946 participants, people with cardiovascular disease) and TRIUMPH-4 (NCT05931367, 445, knee osteoarthritis) are marked completed, and a PubMed search on 3 October 2026 found no primary publication of either; none of the four registry records carries posted results; the company has announced topline results for TRIUMPH-3, which is not the same as a paper. Those are the records checked. The largest peer-reviewed weight-reduction figure for retatrutide is now a Phase 3 one: −25.0% at 80 weeks at 12 mg in TRIUMPH-1. Higher numbers in circulation (28.3% at 80 weeks for the same trial) come from Eli Lilly’s topline announcement made before the paper, not from the paper’s abstract.
The comparison this page is named after has its own trial, and it has not read out either. TRIUMPH-5 (NCT06662383) runs retatrutide against tirzepatide as an active comparator in adults with obesity: 800 participants estimated, primary endpoint percent change in body weight at Week 80, primary completion listed for November 2026. Until it reports, nobody — this page included — can say which performs better, because no trial has yet put them in the same room.
A registry hit is not a study
Searching ClinicalTrials.gov for retatrutide returns a record that should not be counted as evidence, described here rather than quietly dropped because a reader running the same search will find it too. NCT07467447 is registered as a Phase 2 study of once-weekly LY3437943 against placebo in adults with obesity or overweight, and its sponsor — named on the record, so anyone can repeat this — is not the company that developed the compound. That sponsor’s other filings settle it: eight records, every one a mid- or late-phase interventional study, every one listing the same single hospital as its only site, one carrying the words “(Mock Study)” in its own brief title. Two bear on this page — the retatrutide record above, which reproduces the real Phase 2 obesity trial arm for arm, down to the two separate 8 mg escalation schedules and the same Week 24 body-weight primary; and NCT07481747, filed under the acronym SURMOUNT-1 with the same 2,539 participants as the genuine NCT04184622.
None of that makes the underlying science wrong; it makes those entries useless as evidence. A registry record proves only that someone filed a form.
Milligram scale, and what it does to the arithmetic
The two are described at broadly similar milligram scales, which is exactly why the arithmetic trips people up. The approved tirzepatide labeling lists strengths of 2.5, 5, 7.5, 10, 12.5 and 15 mg; retatrutide’s published trials reported maintenance levels of 0.5, 1, 4, 8, 9 and 12 mg across their arms — labeled strengths in one case, trial assignments in the other, and neither a figure for anyone to reproduce. Where the arithmetic genuinely differs is vial size: concentration is vial amount divided by water volume, so the tables below are that division carried out for each compound’s common research presentations.
Tirzepatide vial sizes
| Vial | + 1 mL | + 2 mL | + 3 mL |
|---|---|---|---|
| 10 mg | 10 mg/mL | 5 mg/mL | 3.33 mg/mL |
| 15 mg | 15 mg/mL | 7.5 mg/mL | 5 mg/mL |
| 30 mg | 30 mg/mL | 15 mg/mL | 10 mg/mL |
Retatrutide vial sizes
| Vial | + 1 mL | + 2 mL | + 3 mL |
|---|---|---|---|
| 5 mg | 5 mg/mL | 2.5 mg/mL | 1.67 mg/mL |
| 10 mg | 10 mg/mL | 5 mg/mL | 3.33 mg/mL |
| 20 mg | 20 mg/mL | 10 mg/mL | 6.67 mg/mL |
The trap is the 10 mg vial that appears in both lists: a concentration worked out for one compound looks reusable for the other and is not. What these tables deliberately do not do is run the division the other way against any trial figure above — a milligram number a trial reported in its own population is not a quantity for anyone to reproduce, and converting it into a measurable volume would present it as one. The reconstitution sections of the tirzepatide and retatrutide guides cover the vial sizes each is supplied in, on the same basis.
One thing the label quietly settles
The FDA-approved tirzepatide presentations are not lyophilised powders at all, but ready-to-use clear solutions in single-dose pens and vials and in multi-dose vials and pens. Reconstitution is not part of the approved product, so the lyophilised vials that get reconstituted are research-market material and should never be described as the labeled one. The same label shows why preservation matters in a container entered more than once: the multi-dose presentations, supplying four doses from one container, list benzyl alcohol and phenol among their excipients while the single-dose ones list neither — the principle behind a preserved diluent, set out on the bacteriostatic water page. Medibact supplies USP-grade bacteriostatic water produced in an FDA-registered U.S. facility, for research use only, and is not affiliated with Eli Lilly and Company or with any registrant or trial sponsor named above; those parties are named only because their labeling, registrations and trial records are the primary sources this comparison is built on.
Where this sits in the rest of the reference
FAQ
What is the difference between tirzepatide and retatrutide?
Two things, and the second matters more. Tirzepatide engages two incretin receptors, GIP and GLP-1; retatrutide engages three, adding the glucagon receptor. And tirzepatide has an approved FDA label — Mounjaro, NDA 215866, and Zepbound, NDA 217806 — while retatrutide has none. What is known about tirzepatide can be checked against a label a regulator reviewed; what is known about retatrutide comes from trial reports its sponsor wrote.
Is retatrutide approved anywhere?
Not that this page can find. The U.S. registers were queried directly: Drugs@FDA returns no application, and the openFDA drug-label endpoint returns no record. Beyond the United States it rests on the sponsor's own words rather than a search it did not run — the expanded-access listing NCT07629401 calls it an “investigational GLP-1/GIP/glucagon triple receptor agonist,” and the June 2026 Lancet report of its first published Phase 3 trial calls it “under clinical development.”
Why does the third receptor matter?
Because it acts through a different route. The discovery paper (Coskun and colleagues, Cell Metabolism, 2022) reports that in obese mice the added glucagon-receptor activity increased energy expenditure, on top of the calorie-intake reduction driven through GIP and GLP-1. Whether that becomes an advantage over a dual agonist in humans is what the head-to-head trial was built to answer, and it has not answered it.
Which one produced more weight reduction in trials?
The reported figures are larger for retatrutide, and they are not comparable. Its Phase 2 obesity trial (NCT04881760) reported a mean weight change at 48 weeks of −24.2% in the 12 mg group against −2.1% for placebo; SURMOUNT-1 (NCT04184622) reported −20.9% at 72 weeks in the tirzepatide 15 mg group against −3.1%. Different durations, populations and placebo responses, and a Phase 2 result against a Phase 3 one. Setting those two numbers side by side is the most common error made about this pair. Retatrutide's own Phase 3 obesity trial, TRIUMPH-1 (NCT05929066, NEJM, 29 September 2026), has since reported −25.0% at 80 weeks in the 12 mg group against −3.9% for placebo — still a separate trial, not a comparison with tirzepatide.
Has anyone compared tirzepatide and retatrutide head to head?
One trial is doing exactly that and it has not reported. TRIUMPH-5 (NCT06662383) runs retatrutide against tirzepatide as an active comparator in adults with obesity, primary completion listed for November 2026. Until it reads out, every comparison of these two — this page included — is an assembly of separate trials rather than a comparison.
Why does retatrutide appear in DailyMed if it is not approved?
Because a DailyMed hit is a submitted label document, not an approval. The retatrutide records there are ten Structured Product Labels from a single labeler, a cross-border e-commerce company, several under a brand name appearing nowhere in Drugs@FDA. The drug-code directory separately carries a dozen entries, every one in the “bulk ingredient” category — drug substance, not a cleared product.
Do the two compounds need different reconstitution arithmetic?
No. The arithmetic is one identical line: concentration equals vial amount divided by water volume. What differs is the input, because the two are supplied on the research market in different vial sizes — commonly 10, 15 and 30 mg for tirzepatide, and 5, 10 and 20 mg for retatrutide. Carrying a concentration across from one to the other is an arithmetic error, and the shared 10 mg size is what makes it easy.
Is this medical advice, and what does Medibact supply?
It is not medical advice, not a dosing, route or frequency instruction, and not personal-use guidance. Every trial figure here describes what a published trial reported in its own population. Medibact supplies USP-grade bacteriostatic water produced in an FDA-registered U.S. facility, for research use only, and is not affiliated with Eli Lilly and Company or with any registrant or trial sponsor named on this page.
Educational use only — not medical advice. This guide summarizes information reported in published research and community practice for educational purposes. It is not medical advice and not a recommendation to use any compound. Any doses, schedules, or combinations shown are examples of what has been reported, not instructions for you. Many peptides described here are research compounds that are not FDA-approved for the uses discussed and may be investigational or restricted. Effects, risks, and legal status vary; individual needs and results vary. Consult a qualified, licensed healthcare professional before making any decision. Do not use this content to diagnose, treat, or dose yourself.