Retatrutide vs Survodutide vs Mazdutide: What the Third Receptor Actually Buys

All three add glucagon receptor agonism to GLP-1. Only retatrutide also keeps GIP, making it the triple. The trade-off this page resolves is mechanism against evidence: the drug with the most receptors has the least data.

Mazdutide and survodutide share an identical receptor pairing and land in very different places, and mazdutide is the only one of the three approved anywhere. All sit in the weight loss and metabolic peptides category, with individual records in retatrutide: the 24.2% figure comes from a 338-person phase 2 trial, survodutide: the placebo arm that lost 5.4% and mazdutide: approved in China, misdescribed everywhere else.

What is the actual receptor difference between the three?

Retatrutide is the only triple agonist here, hitting GIP, GLP-1 and glucagon receptors. Survodutide and mazdutide are duals with the identical pairing — glucagon receptor plus GLP-1, no GIP component in either. Mazdutide is widely described as a triple agonist and it is not; that label is simply wrong. Their molecular weights separate cleanly: survodutide 4,232.0, mazdutide 4,476.0 and retatrutide 4,731.0 g/mol, against tirzepatide's 4,813.0.

The mechanism is not a labelling technicality — it determines which lever the drug pulls. Glucagon receptor agonism raises energy expenditure, which is a different mechanism from the appetite suppression GLP-1 provides. GIP agonism is a third thing again, and it is the component tirzepatide pairs with GLP-1. Retatrutide stacks all three; survodutide and mazdutide stack two of them, and the same two.

Sharing a receptor pairing does not mean sharing a profile, which is the most useful single finding in this comparison. Survodutide and mazdutide are pharmacologically the same idea, and they diverge sharply on efficacy, on tolerability and on regulatory status.

The mass separations are hundreds of daltons — trivially resolved by mass spectrometry and completely invisible on an HPLC purity certificate, which reports how pure a sample is rather than what it is. A vial of tirzepatide mislabelled as mazdutide would return a clean purity figure. See mass spectrometry for peptides.

Does adding a third receptor produce more weight loss?

On raw percentages, yes: retatrutide's −24.2% leads mazdutide's −16.65% and survodutide's −13.0%. On evidence tier, the ranking is worthless as it stands. Retatrutide's figure is phase 2 in 338 participants over 48 weeks; the other two are phase 3 trials of 461 and 725 participants. And the placebo arms differ enormously — from a 0.30% gain in GLORY-1 to a 5.4% loss in SYNCHRONIZE-1 — so the raw column is not measuring the same thing three times.

Placebo-adjusted figures that the trial reports do not carry are our own subtraction of the placebo arm from the treatment arm. The 15.15-point mazdutide figure and the 7.6-point survodutide figure are published as such.

Three separate qualifications attach to that table, and each one bites on a different row.

Retatrutide's row is phase 2. Jastreboff et al., NEJM 2023;389(6):514–526 (PMID 37366315), n=338, 48 weeks, 12 mg. As of 11 August 2026 no phase 3 retatrutide results paper exists; the TRIUMPH programme has published a design paper covering four trials and more than 5,800 participants, and nothing else. Phase 2 estimates routinely shrink when populations broaden and dropout rises.

Mazdutide's rows come from Chinese adults. GLORY-1 (Ji et al., NEJM, June 2025, PMID 40421736, NCT05607680) and GLORY-2 (Gao et al., JAMA, 4 August 2026, PMID 42251595, NCT06164873) both enrolled Chinese adults, whose baseline body weight is generally lower than in Western obesity trials. That affects how the percentages transfer, and it is a reason to be cautious about placing them directly alongside SURMOUNT-1 or STEP-1. No trial of mazdutide has been run outside China.

Survodutide's row is distorted by its own control group, which is the next section. Also worth knowing: the higher survodutide dose bought very little — 6.0 mg produced −13.0% against −12.2% at 3.6 mg, with slightly fewer responders at the 5% threshold (71.9% versus 72.6%).

For scale outside this trio: tirzepatide reached −20.9% in SURMOUNT-1 and CagriSema — two drugs combined — reached −20.4% in REDEFINE-1, essentially where tirzepatide alone landed. None of the comparisons on this page is head-to-head. No trial has put any two of these three against each other.

Why is the placebo column the one that decides this table?

Survodutide's SYNCHRONIZE-1 placebo arm lost 5.4% of body weight over 76 weeks, with 46.3% of placebo participants losing at least 5% — roughly double the placebo response in SURMOUNT-1 (−3.1%), STEP-1 (−2.4%) or REDEFINE-1 (−3.0%), and far above GLORY-2's −1.50%. No explanation appears in the abstract. The arithmetic consequence is that survodutide's effect compresses to about 7.6 percentage points, and any ranking on raw percentage is comparing drugs against different baselines.

A 5.4% placebo weight loss over 76 weeks, with nearly half the control group losing at least 5% of body weight, is a much stronger control response than this field usually sees. It could reflect trial-level lifestyle intervention, population characteristics, or trial duration. None of those explanations is confirmed, and the abstract does not address the question.

The direction of the distortion matters more than its size. An unusually responsive placebo arm does not flatter survodutide — it penalises it, because drug effect is measured as the gap between arms. Every leaderboard that ranks raw percentage weight loss is quietly comparing drugs against different baselines, and doing so in exactly the direction that flatters everyone else.

The correction makes the comparison fairer without rescuing survodutide. 7.6 points is genuinely at the lower end of this class, against 15.15 for mazdutide at 9 mg and, from the survodutide trial report's own comparison, 17.8 for tirzepatide and 17.3 for CagriSema. Survodutide's case does not live on the scale.

What does glucagon receptor agonism do that GIP does not?

Glucagon receptor agonism acts directly on hepatocytes to increase fat oxidation, which is a more targeted route to liver fat than weight loss alone, and it raises energy expenditure rather than only suppressing appetite. Survodutide's strongest published result is exactly there: in a 293-patient phase 2 randomised trial in MASH, 62% of patients on 4.8 mg achieved MASH improvement without worsening fibrosis against 14% on placebo, P<0.001. That is phase 2 histology, not a phase 3 outcome.

The trial is Sanyal et al., NEJM, July 2024 (PMID 38847460), with P<0.001 for the primary endpoint on a quadratic dose-response model. Metabolic dysfunction-associated steatohepatitis is a serious condition with very few approved therapies, and a 62% histological response against 14% on placebo is a substantial phase 2 signal in a field with almost nothing in it.

One pattern deserves stating rather than smoothing. The dose response is non-monotonic — 4.8 mg outperformed 6.0 mg on every endpoint in that table. That is common in phase 2 and usually resolves with larger numbers, but it matters for anyone assuming more is better on a compound whose obesity programme titrates to 6.0 mg.

Further survodutide data has published or is in progress: SYNCHRONIZE-MASLD (Nature Medicine, June 2026, PMID 42252333), a SYNCHRONIZE-2 baseline paper (PMID 41216778), a SYNCHRONIZE-CVOT baseline paper in JACC: Heart Failure (PMID 41329105), and work in cirrhosis (Journal of Hepatology, November 2024, PMID 38857788).

Retatrutide's addition of glucagon to GIP and GLP-1 is intended to do the same thing — raise energy expenditure alongside appetite suppression — and its evidence for that is one phase 2 obesity trial. No comparable histological result has been published for retatrutide or mazdutide in the record we hold. Mazdutide's second indication runs the other way, into glycaemia: HbA1c fell 1.57 and 2.15 percentage points at 4 mg and 6 mg over 24 weeks against 0.14% on placebo (n=320, P<0.0001), across two phase 3 papers published in Nature in April 2026.

Which of the three is approved, and where?

Mazdutide is the only one approved anywhere. It holds two marketing authorisations from China's National Medical Products Administration — June 2025 for weight management and September 2025 for glycaemic control in type 2 diabetes — sold as Xinermei® (信尔美). Retatrutide and survodutide are not approved anywhere we could verify, and neither appears on FDA's novel approvals lists for 2025 or 2026. None of the three has ever had a US compounding pathway, because that pathway begins with an approved product.

The primary source for the Chinese approvals is a peer-reviewed drug monograph rather than a press release: Shirley M, "Mazdutide: First Approval," Drugs, December 2025 (PMID 41028652), corroborated by a Lancet Diabetes & Endocrinology review of obesity in China, February 2026 (PMID 41389801). We could not fetch China's NMPA announcement directly — the agency's site returned an error — so we cite "June 2025" rather than the specific date that circulates in vendor copy. Mazdutide's status in markets other than China and the United States we could not confirm in either direction.

Peptigrity's own mazdutide compound page said "Mazdutide is not approved by the FDA or EMA as of May 2026" without mentioning the Chinese approvals. Technically true, substantively misleading, and being corrected.

The compounding logic is identical for all three and worth understanding rather than memorising. Compounding a drug that is essentially a copy of an approved product is permitted only while that product is in shortage. None of these three has ever been approved in the United States, so none has ever been in shortage, so no route has ever existed. None appears on FDA's bulk drug substances compounding tables — we enumerated both on the page current 22 April 2026, and no GLP-1, GIP, glucagon or amylin agonist is on either. That absence carries no permission. FDA has "warned companies that have illegally sold unapproved drugs... falsely labeled 'for research purposes' or 'not for human consumption.'" See the FDA peptide regulation timeline and compounding pharmacy versus research peptide.

The sport position is a genuine asymmetry, and it turns entirely on the Chinese approval. WADA's 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." Retatrutide and survodutide hold no approval anywhere, so on the plain text S0 captures them. Mazdutide holds an approval from a governmental regulatory health authority, so S0 does not obviously apply to it. That is our reading of the text rather than a published ruling, and an athlete should seek a determination.

Which of the three is best tolerated?

Mazdutide, on the only tolerability metric published for all the trials that report one. Discontinuation due to adverse events ran 0.5% to 2.9% across mazdutide's phase 3 obesity trials against 6.2% for tirzepatide in SURMOUNT-1 — the lowest in this class by a wide margin. Survodutide produced gastrointestinal adverse events in 80.9% and 89.7% of participants, the worst here. Neither survodutide nor retatrutide reports a discontinuation rate, so the comparison is genuinely incomplete rather than close.

Mazdutide's combination is unusual enough to state twice: gastrointestinal adverse event rates that are not low at all, alongside the lowest discontinuation figures in this drug class. Those two normally move together. Three explanations are available and none has been tested — the population, the titration schedule, or something about the molecule. Nothing in the published record distinguishes between them, and no trial outside China exists to test whether the figure travels.

Survodutide's number is missing rather than bad, and the distinction is load-bearing. Nearly nine out of ten participants on 6.0 mg had gastrointestinal adverse events, but how many stopped because of it is unknown. That gap limits what can be claimed in both directions: it does not mean survodutide was well tolerated, and it does not mean it was abandoned. It means the number does not exist in the published abstract, and we are not quoting one.

Retatrutide's absence is the most consequential of the three, because glucagon receptor agonism adds nausea and vomiting risk on top of an already emetogenic class and the phase 2 abstract does not say how many people left. Every drug in this class shows its tolerability problem at scale, not in a 338-person study. See peptide side effects and retatrutide side effects.

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

The testing depth is inverted against the evidence. Retatrutide carries 1,150 independent tests at 99.67% average purity, survodutide 37 at 99.59% and mazdutide 30 at 99.56% (verified August 2026) — the least-evidenced compound is the best-characterised vial. Quantity is where all three fail: survodutide's fill variance runs −13% to +36.9%, retatrutide's −4% to +22.5%, and one mazdutide sample labelled 20 mg assayed at 15.18 mg while testing 99.80% pure.

The mazdutide record is the most instructive single result on this platform. An April 2026 sample labelled 20 mg assayed at 15.18 mg — a 24.1% shortfall — while testing 99.80% pure. High purity, badly wrong quantity. The material was what it claimed to be; there was a quarter less of it than the label said, and purity testing found no problem because there was no purity problem to find. See why 10 mg isn't 10 mg.

Survodutide's variance runs the other way and is worse. A fifty-point spread on a compound titrated toward 6.0 mg, where 89.7% of trial participants at that dose had gastrointestinal adverse events, means a vial delivering a third more than the label says is delivering a dose that was never studied — on the molecule with the worst adverse-event profile in this comparison. The gastrointestinal burden reported in SYNCHRONIZE-1 was measured at the correct dose.

Those figures come from the survodutide price page (verified 9 August 2026), the mazdutide price page (verified 10 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.

Nine shops and nine offers is a thin market for mazdutide, and unusually for this category it is one where an approved pharmaceutical version already exists in a major market. Because the fill variance across all three is this wide, calculate volume from the assayed quantity rather than the label where you have it: use the retatrutide calculator or the peptide dosing calculator for the two without a compound-specific tool, and convert per-milligram prices into per-dose cost with the cost-per-dose 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), and trust scores weight community reviews and independently verified HPLC purity equally at 50% each. Aggregate figures sit in the Purity Index and individual results in the lab test database. Vendor-level detail sits on the retatrutide compound page and the survodutide compound page, with the compound-specific walkthrough in where to buy retatrutide.

So which should you choose?

For liver disease, survodutide, on a phase 2 histological result no other compound here matches — 62% MASH improvement against 14% on placebo. For tolerability and regulatory standing, mazdutide, the only one approved anywhere and the only one with a published discontinuation rate, at 0.5% to 2.9%. For raw weight loss, retatrutide leads on paper and on phase 2 evidence alone. For anyone who wants the best-evidenced weight loss in this class, the honest answer is none of these three.

The trial that would settle this

No trial has compared any two of these three against each other, and none is identified in the record we hold — which is what makes every ranking on this page cross-trial. The study that would settle it enrols one population, runs all three arms concurrently, reports discontinuation prospectively, and uses an active comparator rather than three separate placebo groups that lost between +0.30% and −5.4%. Until then, the placebo-adjusted column is the closest available substitute.

Frequently Asked Questions

Is mazdutide a triple agonist?

No. Mazdutide is a dual glucagon receptor and GLP-1 receptor agonist and contains no GIP component at all. Tirzepatide is the GIP/GLP-1 dual and retatrutide is the GIP/GLP-1/glucagon triple. Survodutide uses exactly the same glucagon-plus-GLP-1 pairing mazdutide does, which makes the two of them the closest mechanistic pair in this comparison.

Does the triple agonist actually work better?

On the published numbers it produced more weight loss — 24.2% against 16.65% and 13.0% — but that comes from a phase 2 trial in 338 participants over 48 weeks, while the other two figures come from phase 3 trials of 461 and 725. No trial has compared any two of the three directly, and phase 2 estimates routinely shrink in phase 3.

Why does survodutide look so much worse?

Partly because it is, and partly because its placebo group lost 5.4% — roughly double the placebo response in comparable trials, with 46.3% of controls losing at least 5%. Adjusted for its own control arm, survodutide delivers about 7.6 percentage points against 15.15 for mazdutide at 9 mg. It is genuinely at the lower end, but the raw percentages overstate the gap.

Which one is approved?

Only mazdutide, and only in China. The National Medical Products Administration cleared it for weight management in June 2025 and for glycaemic control in type 2 diabetes in September 2025, marketed as Xinermei®. Retatrutide and survodutide are not approved anywhere we could verify, and mazdutide is an unapproved new drug in the United States.

Which is best tolerated?

Mazdutide, on the only figure published across trials that report one: discontinuation for adverse events of 0.5% to 2.9%, against 6.2% for tirzepatide in SURMOUNT-1. Survodutide produced gastrointestinal adverse events in 80.9% to 89.7% of participants but does not report a discontinuation rate, and neither does retatrutide's phase 2 abstract, so the comparison is incomplete rather than close.

Can any of them be legally compounded in the US?

No. Compounding a copy of an approved drug requires that drug to be approved in the United States and in shortage. None of the three has ever been approved there, so none has ever been in shortage, and no such pathway has ever existed. None appears on either FDA bulk drug substances compounding list, and that absence carries no permission.

What the third receptor has and has not shown

Retatrutide, survodutide and mazdutide all pull the glucagon lever, and the drug that pulls three levers has produced the largest number and the smallest evidence base: −24.2% from 338 people in phase 2, with no phase 3 publication, no approval anywhere and no reported discontinuation rate. The two duals that share an identical receptor pairing have landed in completely different places, which is the finding most likely to be useful.

Read by endpoint rather than by receptor count, each has one thing. Mazdutide has an approval, four phase 3 papers and discontinuation under 3%. Survodutide has 62% MASH improvement against 14% on placebo in a disease with almost no approved therapies. Retatrutide has the biggest weight-loss figure in the class and 1,150 lab tests of a drug no regulator has approved anywhere. The supply chains here are better documented than the medicines.

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 or the peptide dosing 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.