Retatrutide vs Tirzepatide vs Semaglutide: One of These Three Numbers Is Phase 2

Ranked by headline weight loss the order is retatrutide, tirzepatide, semaglutide. Ranked by evidence the order inverts. The trade-off this page resolves is efficacy on paper against evidence you can rely on.

Two of these three are approved drugs with phase 3 programmes and one has a single published trial in 338 people. All three sit in the weight loss and metabolic peptides category, and their individual records are in retatrutide: the 24.2% figure comes from a 338-person phase 2 trial, tirzepatide: the dual GIP/GLP-1 agonist that beat semaglutide by 6.5 points and semaglutide: the nausea rate is 44.2%, not 73%.

Which of the three produces the most weight loss?

Retatrutide produced −24.2%, tirzepatide −20.9% and semaglutide −14.9% in their best-published weight-loss trials, which is the ranking every vendor page prints. It is also a ranking across three different evidence tiers: retatrutide's figure is phase 2 in 338 participants over 48 weeks, while the other two come from phase 3 trials enrolling 2,539 and 1,961 people. The leader has never completed a registrational trial anyone can read.

The fourth row is the one most three-way comparisons omit, and it changes the shape of the table. Semaglutide's 7.2 mg dose was approved in March 2026 and produced −20.7% at 72 weeks in STEP UP (n=1,407) against −17.5% on 2.4 mg. On raw percentages that puts semaglutide at its highest approved dose at −20.7%, against tirzepatide's −20.9% in SURMOUNT-1 and retatrutide's phase 2 −24.2%. The gap most people imagine between "the GLP-1 one" and "the good ones" is largely a gap between two doses of the same drug.

Every comparison in that table is cross-trial, not head-to-head. The populations differ, the durations run from 48 to 72 weeks, the placebo arms differ, and the estimands differ. Vendor-level detail sits on the retatrutide compound page, the tirzepatide compound page and the semaglutide compound page.

Why does retatrutide's 24.2% not sit on the same axis?

Retatrutide's 24.2% comes from a phase 2 trial — Jastreboff et al., NEJM 2023;389(6):514–526 (PMID 37366315), n=338, 48 weeks, 12 mg, double-blind and placebo-controlled. The figure is correctly reported; the phase attached to it usually is not. As of 11 August 2026, PubMed contains no phase 3 retatrutide results paper, and phase 2 estimates routinely shrink when populations broaden and dropout rises.

At least 15% weight loss was achieved by 60% to 83% of participants across doses, against 2% on placebo. That is a genuinely striking phase 2 result and nobody should dismiss it. It is also 338 people over 48 weeks — a phase 2 trial doing what phase 2 trials do, which is generate a hypothesis worth testing properly.

The discontinuation rate is not reported in the abstract, and we are not quoting one. That absence matters more than it sounds. Glucagon receptor agonism adds nausea and vomiting risk on top of an already emetogenic class, and every drug in this class shows its tolerability problem at scale rather than in a 338-person study. For the adverse-event picture as reported so far, see retatrutide side effects.

The phase 3 programme has published a design paper and no results. Giblin et al. (Diabetes, Obesity and Metabolism, January 2026, PMID 41090431) describe four registrational trials and more than 5,800 participants: TRIUMPH-1 and TRIUMPH-2 as weight-management basket trials with nested sleep apnoea and osteoarthritis protocols, TRIUMPH-3 in obesity with cardiovascular disease, and TRIUMPH-4 in knee osteoarthritis. None has reported.

Two other figures circulate and neither survives sourcing. The 28% at 80 weeks figure traces to press reporting of a company statement in May 2026, not to a trial publication, and we could not verify it against a primary source. The 30.3% at 104 weeks figure has no source we could find at all. This site's own retatrutide page previously stated that 24.2% came from "Phase 3 TRIUMPH-1" over 80 weeks, with 30.3% at 104 weeks. Both were wrong and both are corrected.

What has actually been compared head-to-head?

Exactly one randomised head-to-head exists among these three, and retatrutide is not in it. SURMOUNT-5 put 751 adults on maximum tolerated doses of tirzepatide and semaglutide for 72 weeks and found −20.2% versus −13.7%, a difference of 6.5 percentage points, P<0.001. Retatrutide has never been compared directly with either drug. A head-to-head against tirzepatide is registered as NCT06662383 and is active and not recruiting, with no results published.

The distinction is not pedantry. Before SURMOUNT-5, the field estimated the tirzepatide–semaglutide gap at roughly two percentage points by comparing SURMOUNT-1's 20.9% against STEP 1's 14.9%. The randomised comparison found 6.5. Cross-trial arithmetic was wrong by a factor of three in the one case where it has been checked, and it happened to be wrong in the direction that understated the difference. There is no reason to assume it is more reliable when applied to a phase 2 result.

What do the three mechanisms actually do?

Semaglutide agonises the GLP-1 receptor alone, tirzepatide adds the GIP receptor, and retatrutide adds glucagon on top of both — a triple agonist. Their molecular weights are 4,113.6, 4,813.0 and 4,731.0 g/mol respectively, which means retatrutide sits 82 daltons below tirzepatide despite having one more receptor target. Glucagon receptor agonism is intended to raise energy expenditure alongside appetite suppression, which is a different lever from eating less.

The mechanistic story is tidy and the evidence for it is uneven. Adding GIP to GLP-1 does appear to produce more weight loss than GLP-1 alone, and SURMOUNT-5 is direct human evidence for that rather than an inference. Adding glucagon on top has produced a larger number in one phase 2 trial, which is a hypothesis rather than a demonstration.

The mass relationships matter for a practical reason. Retatrutide and tirzepatide are 82 daltons apart — a gap a mass spectrometer resolves instantly and an HPLC purity figure does not address at all, because purity measures the proportion of a sample that is the main peak rather than which molecule that peak is. The two are acylated multi-agonist peptides of similar size, stocked by the same shops, listed side by side in the same catalogues. A mislabelled vial does not require anyone to have intended it. See mass spectrometry for peptides.

The retatrutide CAS point is small alone and telling in aggregate. PubChem's record does not expose a CAS number for retatrutide, and the number on vendor pages comes from secondary sources. On this compound, much of what is quoted as specification traces to nowhere authoritative.

Which of the three can you legally obtain?

Two of the three are approved prescription medicines and one is approved nowhere. Tirzepatide holds Mounjaro (NDA 215866) and Zepbound (NDA 217806); semaglutide holds Wegovy and Ozempic. Retatrutide is not approved anywhere we could verify — absent from FDA's drug application database and from FDA's novel approvals lists for 2025 (46 drugs) and 2026 (30 drugs, current through 5 August 2026). All three compounding routes are shut, but for structurally different reasons.

The retatrutide chain is the single most important legal fact here, and it is structurally different from its siblings. Semaglutide and tirzepatide were approved drugs that went into shortage, which is what briefly permitted 503A and 503B compounding of essentially-a-copy versions. Both shortages are now resolved and both routes are closed. Retatrutide never entered that framework at all, because the framework begins with an approved product. Anyone offering "compounded retatrutide" is describing something that has never been lawful.

Belcourt, Sapowadia & White, in Annals of Pharmacotherapy, September 2026, state the consequence for the two approved drugs directly: "With the shortage of innovator semaglutide or tirzepatide products resolved, compounding pharmacies can only legally sell unique products." None of the three appears on FDA's bulk substances compounding tables, and that absence carries no permission whatsoever.

One legitimate non-trial route to retatrutide exists and it does not run through a shop. ClinicalTrials.gov carries NCT07629401, "Pre-approval Expanded Access of Retatrutide," with status AVAILABLE. Expanded access — sometimes called compassionate use — lets patients receive an investigational drug outside a trial, through physicians and the sponsor. It is not approval. See do you need a prescription for retatrutide, compounding pharmacy versus research peptide and the FDA peptide regulation timeline.

The sport position splits the same way and for the same reason. Semaglutide and tirzepatide are absent from the WADA 2026 Prohibited List, and from 1 January 2026 markers of both are monitored in and out of competition. Retatrutide is also unnamed, but the S0 catch-all prohibits substances "with no current approval by any governmental regulatory health authority for human therapeutic use," expressly including "drugs under pre-clinical or clinical development." That is our reading of the plain text rather than a published WADA ruling, and an athlete should seek a determination.

Which is hardest to verify, and what does each cost?

Retatrutide is the hardest to verify and the most tested, which is the inversion at the centre of this comparison. The Purity Index holds 1,150 independent tests on retatrutide at 99.67% average and 930 on tirzepatide at 99.75% (verified August 2026) — more testing on the compound with one published trial than on the compound with a full phase 3 programme. The two sit 82 daltons apart, which no purity figure can separate.

Semaglutide's per-compound purity average and test count are read live from the Purity Index and its price page rather than printed here, because a figure we cannot date is worth less than a page you can refresh. Its failure mode is well characterised even so: FDA states that semaglutide sodium and acetate "are different active ingredients than are used in the approved drugs," so a vial can be 99% pure and hold something no randomised trial has tested.

Those figures come from the semaglutide price page (verified 10 August 2026), the tirzepatide price page (verified 9 August 2026) and the retatrutide price page (verified 31 July 2026). Those figures exclude shipping, taxes and customs, coupon codes, bulk tiers, multi-vial kits and account-gated pricing.

Read that price spread against the evidence rather than against the market. Retatrutide's band is tighter than most compounds on this platform and its supply is deep, which describes a well-organised supply chain rather than a well-evidenced drug. Per-milligram price is also the wrong unit for a three-way comparison, because the three are dosed in different milligram ranges — convert to cost per dose with the cost-per-dose calculator, and work out injection volume with the retatrutide calculator, tirzepatide calculator or semaglutide calculator.

Peptigrity's platform currently tracks 530 shops and 11,852 independent lab tests across 118 peptides, with 1,283 community reviews (verified August 2026). Trust scores weight community reviews and independently verified HPLC purity equally at 50% each, with no financial relationship influencing the ranking. Individual results are searchable in the lab test database, and the compound-specific walkthroughs are where to buy retatrutide, where to buy tirzepatide and where to buy semaglutide. On the gap between purity and quantity, see why 10 mg isn't 10 mg.

One peer-reviewed analysis bears directly on retatrutide sold outside the clinic: Piatkowski, Craven, Cornell & Ferris, "Composition and Labelling Accuracy of Products Sold as Retatrutide in Australia," Drug and Alcohol Review, September 2026, DOI 10.1111/dar.70231. We verified the citation and could not obtain the abstract, so we are not characterising what it concludes.

So which should you choose?

On evidence, tirzepatide — it holds the only randomised head-to-head win in this group, a 2,539-participant phase 3 trial and two approved products. On cardiovascular and liver evidence, semaglutide, which has a 17,604-patient outcomes trial and a MASH indication that neither of the others can match. On measured weight loss, retatrutide leads at −24.2% against tirzepatide’s −20.9% and does so from a phase 2 trial in 338 people, with no approval, no phase 3 publication and no reported discontinuation rate.

The trial that would settle this

NCT06662383 is the trial that would settle this — a registered head-to-head of retatrutide against tirzepatide, active and not recruiting, with no results published. Until it reports, retatrutide's lead is a cross-trial inference drawn from a 338-person phase 2 study against a 2,539-person phase 3 one. The TRIUMPH programme's four registrational trials and more than 5,800 participants have produced a design paper and nothing else.

Frequently Asked Questions

Is retatrutide really better than tirzepatide?

Nobody knows, because the comparison has not been run. Retatrutide's 24.2% comes from a phase 2 trial in 338 participants over 48 weeks, while tirzepatide's 20.9% comes from a phase 3 trial in 2,539 participants over 72 weeks. A head-to-head is registered as NCT06662383 and is active and not recruiting, with no results published.

Why does the phase matter so much?

Because phase 2 estimates routinely shrink in phase 3. Populations broaden, adherence falls, dropout rises and the estimand changes. The one time cross-trial arithmetic was checked against a real head-to-head in this class — tirzepatide against semaglutide — it was wrong by a factor of three, so there is no basis for treating it as reliable on a phase 2 number.

Where does the retatrutide 28% figure come from?

Press reporting of a company statement in May 2026, not a trial publication. We could not verify it against a primary source and are not treating it as established. A separate 30.3%-at-104-weeks figure has no source we could find at all, and this site's own page carried both errors until they were corrected.

Can I get any of the three legally?

Semaglutide and tirzepatide are prescription medicines, so yes, with a prescriber. Retatrutide is not approved anywhere we could verify, and because it has never been approved it has never been in shortage, so no compounding route has ever existed for it. The one non-trial clinical route is expanded access under NCT07629401, which runs through physicians and the sponsor rather than through vendors.

How do you tell retatrutide from tirzepatide in a vial?

Mass spectrometry on your batch, showing a mass near 4,731.0 Da rather than 4,813.0. The 82-dalton gap is trivial for the instrument and invisible to an HPLC purity figure, which reports how much of a sample is the main peak without identifying it. A certificate with a purity number and no mass result has not answered the question.

Does semaglutide belong in this comparison at all?

Yes, and more strongly than the usual ranking suggests. At 2.4 mg it produced 14.9% in STEP 1, but the 7.2 mg dose approved in March 2026 produced 20.7% at 72 weeks in STEP UP, against tirzepatide's 20.9% in SURMOUNT-1. It also holds cardiovascular and MASH indications neither of the other two has.

What the leaderboard hides

The three-way ranking of retatrutide, tirzepatide and semaglutide is real as arithmetic and misleading as evidence. −24.2% sits at the top of it from a 338-person phase 2 trial; −20.9% sits second from a 2,539-person phase 3 trial; and the drug in third place has a 7.2 mg dose that reached −20.7% in its own phase 3. Sorting by headline percentage sorts by how much has been claimed, not by how much has been shown.

What the leaderboard also hides is the supply-side inversion. This platform holds 1,150 independent lab tests on the compound no regulator has approved anywhere and 930 on the compound with the deepest trial programme in the class. The supply chain for retatrutide is better characterised than the medicine is, and a purity certificate is not a substitute for a phase 3 result.

Browse the weight loss and metabolic peptides category, or our complete peptide guide with 118 compounds (verified August 2026). For per-injection volume, use the retatrutide calculator, tirzepatide calculator or semaglutide calculator alongside the reconstitution calculator. Compare shops through independent lab tests and community-verified shop reviews.

This article is for educational and informational purposes only and does not constitute medical advice. Peptides discussed may be investigational compounds not approved by the FDA (or equivalent regulators in your jurisdiction) for human use. Always consult a qualified healthcare provider before using any peptide or research compound. Peptigrity is an independent review platform and does not sell, endorse, or recommend specific products or vendors.