Mazdutide Research, Specifications & Scientific Information

Introduction

Mazdutide occupies a position no other compound in this library does: it is an approved medicine that is not approved in the United States. Its first marketing authorisation came from China's regulator in June 2025, followed by a second Chinese indication that September ^[2]. The U.S. Food and Drug Administration has approved it for nothing.

That distinction is not a technicality on a page like this one. It is the cleanest available demonstration of what a regulatory approval is — a decision by one authority, about one finished product, for one indication, in one jurisdiction — and of what it is not, which is a statement about a molecule that travels with the molecule.

Pharmacologically, mazdutide is an analogue of oxyntomodulin, the gut peptide that naturally activates the glucagon receptor and the GLP-1 receptor together. It was developed by Eli Lilly and Company under the code LY3305677 and, for the Chinese market, by Innovent Biologics as IBI362, which is why the literature carries it under two development codes.

This page is a reference record. It sets out what has been published about mazdutide's structure, its receptor pharmacology, and the preclinical and clinical literature, with every source resolved against PubMed, Crossref or ClinicalTrials.gov at the time the page was built. It describes research. It does not describe use in people or animals, and it carries no guidance of any kind on handling the material.

What Is Mazdutide?

Mazdutide is a synthetic acylated peptide analogue of oxyntomodulin, administered once weekly in every trial in its registrational programme.

Its regulatory position needs to be stated in full, because half of it is routinely quoted without the other half.

It is approved in China. The approvals are for long-term body-weight management in adults meeting defined body-mass index thresholds, in combination with diet control and increased physical activity, and for glycaemic control in adults with type 2 diabetes ^[2].

It is not approved in the United States. No U.S. Food and Drug Administration approval exists for mazdutide in any indication. A marketing approval granted by one national authority has no legal or evidentiary force in another jurisdiction, and it confers nothing at all on research-grade material supplied for laboratory use anywhere.

Functionally it is a dual receptor agonist at the GLP-1 and glucagon receptors ^[1]. Structurally it belongs to the glucagon–secretin peptide superfamily.

Mazdutide Specifications

The 34-residue string above is the backbone recorded for mazdutide in the FDA/NCATS Global Substance Registration System under UNII MB76Z4IBZ5, written in single-letter code. Every letter in that string is a standard amino acid, which distinguishes mazdutide's register entry from those of survodutide, semaglutide and tirzepatide, whose position-2 or position-8 residues have no single-letter representation. The register nonetheless carries structural modifications for this substance, and its own calculated mass for the bare 34-residue chain is approximately 3790 g/mol against the approximately 4476 g/mol carried by PubChem CID 167312357 for the complete molecule — a difference of roughly 690 daltons that is the modification chemistry rather than a discrepancy. The two registers also carry different formulae, C207H317N45O65 in PubChem against C210H328O69N46 in the Global Substance Registration System, and both are shown here rather than reconciled. Mazdutide is described in the literature as an analogue of oxyntomodulin, the natural gut peptide that activates the glucagon and GLP-1 receptors together. Any figure on this page is a reference value: the certificate of analysis supplied with a laboratory order is the record for a given lot.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does Mazdutide Work?

Both of mazdutide's targets are class B1 G protein-coupled receptors and both couple through Gs to raise intracellular cyclic AMP. They sit in different tissues and drive different processes.

The GLP-1 receptor arm is the familiar incretin pharmacology: receptors on pancreatic islet cells and at sites in the central nervous system, whose activation modulates glucose-dependent insulin secretion, slows gastric emptying and reduces calorie intake.

The glucagon receptor arm is the addition. Glucagon receptor signalling in the liver raises whole-body metabolic rate and alters hepatic lipid handling, and unopposed it raises blood glucose — the reason this receptor was avoided in diabetes work for decades. The premise of the dual agonist class is that the incretin arm holds glucose in check while the glucagon arm reaches processes the incretin arm does not.

Mazdutide's particular claim within that class is its template. Oxyntomodulin activates both receptors naturally and is cleared within minutes; mazdutide is an analogue of it, built to persist. What the compound does not attempt is a third receptor: the GIP receptor engaged by tirzepatide and retatrutide is not a mazdutide target.

Mazdutide Mechanism of Action

In vitro research

The cell-based work published for this compound is hepatic rather than receptor-pharmacological, and it is worth being clear about that gap: a primary in vitro characterisation of mazdutide's relative potencies at the two receptors — the equivalent of what was published for survodutide and retatrutide at discovery — is not present in the peer-reviewed record indexed here. What is published describes what the compound does to hepatocytes rather than how tightly it binds.

In a cellular model of steatotic liver disease, established by treating hepatocytes with 1 mM free fatty acids for 24 hours, mazdutide at 10, 20 or 50 nM was compared against the endoplasmic reticulum stress inhibitor 4-phenylbutyric acid. Mazdutide reduced markers of lipid accumulation and inflammation in that model, and acted through the protein kinase R-like endoplasmic reticulum kinase pathway, suppressing nuclear factor kappa B-mediated inflammatory signalling and downregulating the lipogenic regulators sterol regulatory element-binding protein 1, CCAAT/enhancer-binding protein beta and peroxisome proliferator-activated receptor gamma ^[5].

Two cautions belong with that. A hepatocyte loaded with free fatty acids for a day is a model of steatosis in the way a bruise is a model of a fracture, and the concentrations used are chosen by the experimenter. And a mechanism demonstrated in cells is a hypothesis about the intact liver, not a finding in one.

Analytical characterisation of supplied material is a separate exercise from receptor pharmacology and relies on liquid chromatography with mass spectrometric detection against a reference standard rather than on any biological assay.

What Is Mazdutide Being Researched For?

Registered clinical research on mazdutide has covered:

• Obesity and overweight in Chinese adults — two reported phase 3 trials ^{[1, 6]}.
• Type 2 diabetes in Chinese adults — two reported phase 3 trials, one against placebo and one against an active comparator ^{[3, 4]}.
• Obesity and overweight in United States adults — a reported phase 2 trial across a wider amount range than the Chinese programme used ^[7].
• Metabolic dysfunction-associated fatty liver disease, a respiratory indication, and alcohol use disorder — registered clinical evaluation, not yet reported in the sources cited here ^[2].

Each of those is research into a pharmaceutical product candidate, conducted by its sponsor under a registered protocol. None of it is research into, or evidence about, research-grade material supplied for laboratory use.

Human Research on Mazdutide

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

GLORY-1 — phase 3 in Chinese adults with obesity or overweight

Population. 610 participants aged 18 to 75 in China with a body-mass index of at least 28, or 24 to under 28 with at least one weight-related coexisting condition. Mean body mass 87.2 kg, mean body-mass index 31.1 at baseline ^{[1, 9]}.

Endpoint and duration. Two primary endpoints at week 32: the percentage change in body mass from baseline, and a reduction of at least 5%, assessed on a treatment-policy estimand that counts effects regardless of early discontinuation or the initiation of new therapies. Randomised 1:1:1 to mazdutide 4 mg, mazdutide 6 mg or placebo for 48 weeks ^[1].

Result. At week 32, mean percentage change in body mass was −10.09% (95% CI −11.15 to −9.04) at 4 mg, −12.55% (−13.64 to −11.45) at 6 mg and +0.45% (−0.61 to 1.52) with placebo; reductions of at least 5% occurred in 73.9%, 82.0% and 10.5% respectively, P < 0.001 for all comparisons. At week 48 the figures were −11.00%, −14.01% and +0.30%, with reductions of at least 15% in 35.7%, 49.5% and 2.0% ^[1].

Adverse events. Most frequently gastrointestinal and mostly mild to moderate. Discontinuation for adverse events was 1.5% at 4 mg, 0.5% at 6 mg and 1.0% with placebo ^[1].

Limitations. Conducted entirely in China, in a population whose mean body-mass index of 31.1 is well below that of participants in the obesity trials of comparable compounds elsewhere; the eligibility thresholds are the Chinese ones, which are lower. Results in this population do not transfer automatically to others. Forty-eight weeks, with an anthropometric endpoint rather than a clinical outcome.

GLORY-2 — phase 3 at an expanded weekly amount

Population. 461 Chinese adults who received treatment (307 mazdutide, 154 placebo), with obesity defined as a body-mass index of 30 or above, with or without type 2 diabetes; 64.0% female, 16.1% with type 2 diabetes, mean age 33.9 years, mean body mass 94.0 kg, mean body-mass index 34.3. Twenty-seven hospitals, December 2023 to November 2025 ^{[6, 12]}.

Endpoint and duration. Co-primary outcomes at week 60: the percentage change in body mass from baseline, and a reduction of at least 5%. Randomised 2:1 to mazdutide 9 mg weekly or placebo, alongside a reduced-calorie diet and increased physical activity ^[6].

Result. At week 60, mean percentage change in body mass was −16.65% (95% CI −18.19 to −15.12) with mazdutide against −1.50% (−3.43 to 0.43) with placebo, a between-group difference of −15.15% (−17.22 to −13.09), P < .001. A reduction of at least 5% occurred in 84.3% against 33.1%, difference 51.6 percentage points, P < .001 ^[6].

Adverse events. Vomiting in 53.1% against 1.3%, nausea in 46.9% against 3.2%, diarrhoea in 39.4% against 6.5%; most mild to moderate. Discontinuation for adverse events occurred in 2.9% against 0% ^[6].

Limitations. The adverse event figures are the striking ones: more than half of participants vomited. The authors state the trade-off directly in their conclusion. Mean age 33.9 years is young for an obesity trial, and the 33.1% of placebo participants reaching a 5% reduction is high.

DREAMS-1 — phase 3 monotherapy in type 2 diabetes

Population. 320 Chinese adults with type 2 diabetes inadequately controlled by diet and exercise alone. Mean glycated haemoglobin 8.24%, body-mass index 28.2 kg/m², diabetes duration 1.9 years ^{[3, 10]}.

Endpoint and duration. Primary endpoint the change in glycated haemoglobin at week 24, randomised 1:1:1 to mazdutide 4 mg, 6 mg or placebo, followed by a 24-week extension in which all participants received mazdutide ^[3].

Result. At week 24, glycated haemoglobin fell by 1.57% at 4 mg and 2.15% at 6 mg against 0.14% with placebo — treatment differences of −1.43% and −2.02%, both P < 0.0001. Change in body mass was −5.61% and −7.81% against −1.26%, both P < 0.0001. More participants on mazdutide reached glycated haemoglobin below 7.0%, a body-mass reduction of at least 5%, and the composite of both ^[3].

Adverse events. The most common were diarrhoea, decreased appetite and nausea, which the authors describe as consistent with the GLP-1 receptor agonist class ^[3].

Limitations. A monotherapy trial with a placebo comparator over 24 weeks, in a population with a mean diabetes duration of 1.9 years — early disease, and the easiest population in which to show a glycaemic effect.

DREAMS-2 — phase 3 against dulaglutide

Population. 731 Chinese adults with type 2 diabetes on background oral antidiabetic therapy ^{[4, 8]}.

Endpoint and duration. Change in glycated haemoglobin from baseline to week 28, randomised 1:1:1 to mazdutide 4 mg, mazdutide 6 mg or dulaglutide 1.5 mg ^[4].

Result. Both mazdutide groups met non-inferiority and superiority against dulaglutide 1.5 mg, with least-squares mean treatment differences of −0.24% (P = 0.0032) at 4 mg and −0.30% (P = 0.0003) at 6 mg. Reductions in body mass were greater with mazdutide, differences of −3.78% and −5.76% against dulaglutide, both P < 0.0001. More participants on mazdutide reached the composite of glycated haemoglobin below 7.0% with a body-mass reduction of at least 5%, both P < 0.0001 ^[4].

Adverse events. The most common treatment-emergent events were diarrhoea, nausea and vomiting, and their incidence was higher with mazdutide than with dulaglutide ^[4].

Limitations. The comparator is dulaglutide at 1.5 mg, not at the higher amounts subsequently studied for that compound, so the comparison is against a specific regimen rather than against the comparator at its maximum. Twenty-eight weeks, entirely in China.

United States phase 2 in obesity or overweight

Population. 179 participants at 24 United States centres, aged 18 to 75 without type 2 diabetes, with a body-mass index of 30 kg/m² or higher, or 27 to under 30 with at least one weight-related comorbidity. Mean age 47.7 years; 66% female ^{[7, 11]}.

Endpoint and duration. Primary endpoint the percentage change in body mass from baseline to 32 weeks, evaluated on the efficacy estimand, within a 48-week randomised, double-blind, placebo-controlled trial. Four arms: placebo, or mazdutide at 3–6 mg, 10 mg or 16 mg weekly ^[7].

Result. At 32 weeks, least-squares mean percentage change in body mass was −7.3% (SE 0.9) in the 3–6 mg group, −15.6% (0.7) at 10 mg and −18.1% (1.0) at 16 mg, against −0.9% (0.8) with placebo. Estimated treatment differences against placebo ranged from −6.5% to −17.2%, P < 0.0001 for all. Further reductions were observed at 48 weeks ^[7].

Adverse events. Mostly gastrointestinal and mild to moderate. Discontinuation for adverse events was most frequent at 16 mg, at 20%, primarily for gastrointestinal disorders ^[7].

Limitations. Phase 2, 179 participants. The weekly amounts studied here — up to 16 mg — are far above the 4, 6 and 9 mg used in the Chinese phase 3 programme, so the two bodies of evidence are not describing the same regimen. A 20% discontinuation rate at the highest amount is the constraint that governs how the result should be read.

Preclinical Research on Mazdutide

Animal research

The published animal work for this compound is about the liver, and it followed rather than preceded the clinical programme — which is itself worth noting, since it means the mouse data were not what justified the human trials.

A steatotic liver disease model was induced in mice by twelve weeks of a high-fat diet, followed by four weeks of subcutaneous mazdutide at 100, 200 or 400 µg/kg. Compared with the untreated model group, treated mice showed improvement in systemic and hepatic lipid profiles, reduced liver injury markers and reduced hepatic steatosis on histology, and reduced markers of inflammation and oxidative stress, all p < 0.05 ^[5].

The mechanistic analysis ran in parallel across mice and hepatocytes: relief of endoplasmic reticulum stress through the protein kinase R-like endoplasmic reticulum kinase pathway, suppression of nuclear factor kappa B-mediated inflammation, and downregulation of sterol regulatory element-binding protein 1, CCAAT/enhancer-binding protein beta and peroxisome proliferator-activated receptor gamma ^[5].

Two things bound this. A high-fat-diet mouse is a model of early steatosis and not of the fibrotic disease that determines outcome in people. And the study examined the compound against a disease model rather than characterising its receptor pharmacology, so it says what mazdutide did in that model and not through which of its two receptors it did it.

Findings described in this section were observed in animals. Nothing in them establishes anything about humans.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Mazdutide vs Related Compounds

The distinctions between mazdutide and the compounds it is usually set beside are which receptors each engages and where each is approved, and nothing else is stated here.

Receptor agonism

Mazdutide — GLP-1R and GCGR. Survodutide and pemvidutide — the same pair. Tirzepatide — GIPR and GLP-1R, a different pair. Retatrutide — GIPR, GLP-1R and GCGR. Semaglutide — GLP-1R alone.

Template

Mazdutide is described as an analogue of oxyntomodulin, the natural peptide that activates both of its targets. Survodutide's discovery paper names the same template. That shared premise does not make the two molecules interchangeable, and no trial has compared them.

Register legibility

Mazdutide's recorded backbone contains only standard amino acids, unlike survodutide's, semaglutide's and tirzepatide's, whose register strings carry a placeholder letter at a modified position. That is a fact about the register entries, not a statement about which molecule is better characterised.

Regulatory position

Mazdutide is approved in China and not in the United States ^[2]. Semaglutide, tirzepatide and dulaglutide are active ingredients of products approved in the United States. Survodutide, pemvidutide and retatrutide are investigational everywhere. Approval is specific to a jurisdiction, a product and an indication.

No comparison of effect between these compounds is made on this page. Where head-to-head trials exist they are registered, and their results belong to the papers that report them.

Chemical & Molecular Characteristics

Mazdutide is a modified 34-residue peptide. The backbone recorded in the FDA/NCATS Global Substance Registration System under UNII MB76Z4IBZ5 is HGQGTFTSDYSKYLDEKKAKEFVEWLLEGGPSSG.

Three points qualify that string.

Every letter is a standard amino acid — and the molecule is still modified. This is the unusual feature of mazdutide's register entry. Where survodutide's recorded backbone contains an X for a residue with no single-letter code, mazdutide's does not. The register nevertheless carries structural modifications for the substance, and the reader should not conclude from a clean-looking string that the molecule is an unmodified peptide.

The mass difference locates the modification. The register's calculated mass for the bare 34-residue chain is approximately 3790 g/mol; PubChem compound identifier 167312357 carries approximately 4476 g/mol for the complete molecule. The roughly 690-dalton gap between them is the modification chemistry — consistent with the fatty-acid acylation and linker that this family of once-weekly peptides uses, though the register does not spell out the structure in the way the discovery literature does for other compounds in this category.

The registers disagree on the formula. PubChem carries C207H317N45O65; the Global Substance Registration System carries C210H328O69N46. Both are shown on this page rather than reconciled. CAS registry number 2259884-03-0 is carried by both and is consistent. Two development codes also circulate — LY3305677 from the originator and IBI362 from the Chinese developer — and both refer to the same substance.

Frequently Asked Questions

Scientific References

1. Ji L, Jiang H, Bi Y, et al.. Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight The New England journal of medicine; 2025. PMID 40421736 doi:10.1056/NEJMoa2411528
2. Shirley M. Mazdutide: First Approval Drugs; 2025. PMID 41028652 doi:10.1007/s40265-025-02249-y
3. Zhu D, Zhao J, Cai H, et al.. Mazdutide versus placebo in Chinese adults with type 2 diabetes Nature; 2026. PMID 41407859 doi:10.1038/s41586-025-10026-w
4. Guo L, Zhang B, Xue X, et al.. Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes Nature; 2026. PMID 41407860 doi:10.1038/s41586-025-10031-z
5. Gan L, Duan L, Zheng X. Mazdutide Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease by Modulating Endoplasmic Reticulum Stress, Improving Lipid Metabolism and Alleviating Inflammation Pharmaceuticals (Basel, Switzerland); 2026. PMID 41901218 doi:10.3390/ph19030371
6. Gao L, Jiang H, Cai H, et al.. Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial JAMA; 2026. PMID 42251595 doi:10.1001/jama.2026.8142
7. Hsia SH, Bays HE, Billings LK, et al.. Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based, multicentre, phase 2, randomised, placebo-controlled clinical trial The lancet. Diabetes & endocrinology; 2026. PMID 42628555 doi:10.1016/S2213-8587(26)00160-9
8. A Study of IBI362 in Participants With Type 2 Diabetes 2023. NCT05606913
9. A Study of IBI362 in Participants With Obesity or Overweight 2022. NCT05607680
10. A Study of IBI362 in Poorly Controlled Type 2 Diabetes Patients Only Through Diet and Exercise 2023. NCT05628311
11. A Study of LY3305677 Compared With Placebo in Adult Participants With Obesity or Overweight 2023. NCT06124807
12. A Study of IBI362 9 mg in Chinese Adults With Obesity 2023. NCT06164873

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.