Mazdutide Guide: Evidence & Sourcing

Mazdutide at a glance

What it is

Mazdutide (development codes IBI362 and LY3305677), a once-weekly glucagon-receptor and GLP-1-receptor dual agonist. Indexed as MeSH supplementary concept C000719829, which lists mazdutide, IBI362 and LY3305677 as the same substance. No molecular formula or mass is published on this page: PubChem's REST service returned a server-busy fault on every attempt while this page was written, and an unverified formula is worse than none

Researched for

Long-term weight management and type 2 diabetes — both approved indications in China — plus ongoing clinical evaluation in metabolic dysfunction-associated fatty liver disease, obstructive sleep apnoea and alcohol use disorder

Published trial doses

4 mg and 6 mg once weekly in GLORY-1 and in both DREAMS phase 3 trials; 9 mg once weekly in GLORY-2; 3 mg, 4.5 mg and 6 mg in the phase 2 programme; a 32-person phase 1 escalated to 16 mg. No trial started a participant at its maintenance dose

Half-life

Measured in three published studies, and it varies widely between people: after a first dose, 6.3 to 16.8 days (EClinicalMedicine 2021, PMID 34430840) and 7.3 to 44.8 days (EClinicalMedicine 2022, PMID 36247927), with peak levels at a median of about 72 hours; about 8 days after 20 weeks at the top dose of a US study (PMID 40832785). Every phase 2 and phase 3 trial dosed once weekly

Regulatory status

Approved in China: June 2025 for long-term weight management in adults with a BMI of at least 28, or at least 24 with a weight-related comorbidity, and September 2025 for glycaemic control in type 2 diabetes. Marketed as Xinermei. Not approved in the United States or the European Union. Sold and referenced here for research use only

Educational reference. This page does not publish dose ranges or reconstitution arithmetic.

What it is / mechanism

Mazdutide is a synthetic peptide that activates two receptors at once: the glucagon receptor (GCGR) and the glucagon-like peptide-1 receptor (GLP-1R). It is built on the oxyntomodulin scaffold — oxyntomodulin is the naturally occurring gut hormone that happens to hit both of those receptors — which is a different design lineage from tirzepatide, whose second receptor is GIP rather than glucagon. The two development codes are the single most common source of confusion about this compound, and they are not two molecules. IBI362 is Innovent Biologics' code and LY3305677 is Eli Lilly's; the two companies co-developed it, and the MeSH supplementary concept record C000719829 lists mazdutide, IBI362 and LY3305677 as names for one substance. A vial labelled IBI362 and a vial labelled LY3305677 are labelled for the same thing, which is worth knowing before paying a premium for one designation. The glucagon arm is the part that inverts most people's intuition. Glucagon is known as the hormone that raises blood glucose, so adding glucagon-receptor agonism to a diabetes drug reads like a mistake. The dual-agonist rationale is that glucagon-receptor signalling contributes increased energy expenditure and direct effects on hepatic fat handling, while the GLP-1 arm supplies appetite suppression, slowed gastric emptying and glucose-dependent insulin secretion — and offsets the glycaemic effect of the glucagon arm. The DREAMS-1 result is the cleanest evidence that the offset works in practice: mazdutide monotherapy lowered HbA1c by 1.57 to 2.15 percentage points against 0.14 on placebo, which is not what a net glucagon agonist would do. That hepatic mechanism is also why the programme extends past obesity and diabetes into metabolic dysfunction-associated fatty liver disease, obstructive sleep apnoea and alcohol use disorder — indications a pure appetite-suppression mechanism would not obviously reach.

Researched effects

Mazdutide is one of the few compounds in this library where the answer to "what does it do" comes from phase 3 trials that a regulator has already reviewed, so the numbers are worth quoting rather than summarising. GLORY-1 (NCT05607680, published in the New England Journal of Medicine in 2025) randomised 610 Chinese adults with a BMI of at least 28, or 24 to under 28 with a weight-related coexisting condition, to 4 mg mazdutide, 6 mg mazdutide or placebo for 48 weeks. Mean baseline weight was 87.2 kg and mean BMI 31.1. At week 32 the mean change in body weight was -10.09% on 4 mg and -12.55% on 6 mg, against +0.45% on placebo, and 73.9%, 82.0% and 10.5% of participants respectively had lost at least 5%. By week 48 the figures were -11.00% and -14.01% against +0.30%, with at least 15% lost by 35.7%, 49.5% and 2.0%. GLORY-2 (NCT06164873, published in JAMA in 2026) is the trial that tested the higher dose. It randomised Chinese adults with a BMI of at least 30 in a 2:1 ratio to 9 mg mazdutide or placebo for 60 weeks across 27 hospitals; 461 participants were analysed, mean age 33.9, mean BMI 34.3, 16.1% with type 2 diabetes. At week 60 the mean change in body weight was -16.65% against -1.50% on placebo, a between-group difference of -15.15 percentage points, and 84.3% versus 33.1% had lost at least 5%. Two things in that second result deserve more attention than the headline. The first is that 33.1% of the placebo group lost at least 5% of body weight — both trials ran alongside a reduced-calorie diet and increased physical activity, and in GLORY-2 that background alone moved a third of the placebo arm past the 5% threshold. The second is the cost of the 9 mg dose, which is in the safety section below and is the part of this compound's record most often left out. In type 2 diabetes the two DREAMS phase 3 trials reported separately. Against placebo (320 participants, 24 weeks) mazdutide lowered HbA1c by 1.57 percentage points at 4 mg and 2.15 at 6 mg, against 0.14 on placebo, with weight changes of -5.61% and -7.81% against -1.26%. Against dulaglutide 1.5 mg (731 participants, 28 weeks) both doses were superior on HbA1c by 0.24 and 0.30 percentage points, and on body weight by 3.78 and 5.76 percentage points.

Research timeline

Dated milestones taken from the primary records: the molecule's discovery, its first registered human study, the trials that shaped the evidence and the regulatory decisions. Each entry links to the record it comes from.

1. Aug 13, 2021The first published trial of IBI362, the Innovent Biologics molecule also coded LY3305677, gives three rising doses or placebo to 36 Chinese adults with overweight or obesity for 12 weeks; no serious adverse event is reported. PMID 34430840
2. Dec 14, 2023A phase 2 trial at 20 Chinese hospitals randomizes 248 adults with overweight or obesity to mazdutide or placebo for 24 weeks; every mazdutide arm loses clearly more weight than placebo, and diarrhoea and nausea are the commonest side effects. PMID 38092790
3. May 25, 2025GLORY-1, the first phase 3 trial, published in the New England Journal of Medicine, randomizes 610 Chinese adults with obesity or overweight to two doses of mazdutide or placebo; at week 32 both doses produce clinically relevant weight loss against almost none on placebo. PMID 40421736
4. Dec 17, 2025Two phase 3 trials in Chinese adults with type 2 diabetes appear together in Nature: against placebo in 320 people, mazdutide lowers HbA1c and weight at week 24, and against the approved GLP-1 drug dulaglutide it lowers both further at week 28, with more gastrointestinal side effects. PMID 41407859
5. Aug 4, 2026GLORY-2, published in JAMA, tests a higher dose in 461 Chinese adults with moderate to severe obesity for 60 weeks; weight loss is clinically meaningful, but vomiting affects about half of those on mazdutide, against 1% on placebo. PMID 42251595
6. Aug 21, 2026The first trial outside China, a 48-week phase 2 study funded by Eli Lilly at 24 US centres in 179 adults with obesity or overweight, reports clinically meaningful weight loss at every dose tested, with more at the higher doses. PMID 42628555

Records checked Oct 4, 2026

Claims at a glance

The claims most often made about this compound, each with the strongest kind of evidence we found for it. The grade says what was studied, not whether the claim is true; the line beside it says what that study showed.

• Causes substantial weight lossHuman, randomised trial. In a 48-week phase 3 trial of 610 Chinese adults, weight fell about 11–14% against essentially no change on placebo, counting people who stopped. PMID 40421736
• Controls type 2 diabetes better than older GLP-1 drugsHuman, randomised trial. In a 28-week phase 3 of 731 people against dulaglutide, HbA1c fell slightly more and weight considerably more. PMID 41407860
• Works better than semaglutideNo study found. The one completed head-to-head trial, 349 people, open-label, has published only its design and baseline data; no comparison result exists yet. NCT06184568
• Clears fat from the liverAnimal studies only. The clearest liver-fat imaging is in mice on a high-fat diet; in people only liver enzymes, an indirect marker, have been reported. PMID 40828048
• Protects memory and thinkingAnimal studies only. Behaviour improved in male diabetic mice; a trial in people with type 2 diabetes and early cognitive impairment is still recruiting. PMID 40479843
• Protects the heartNo study found. None of the 43 registry records for mazdutide is a cardiovascular outcome trial; published trials report blood pressure and lipids, which are risk markers, not heart events. ClinicalTrials.gov search, Oct 6, 2026

The reasoning behind each grade, study by study, is in this guide's Benefit & Outcome Review.

Grades checked Oct 6, 2026

Half-life & pharmacokinetics

Mazdutide's half-life has been measured in three published studies, and the honest answer is a range rather than a single number. The first published human study (EClinicalMedicine 2021, PMID 34430840; NCT04440345) measured it after the first dose in 24 Chinese adults with overweight or obesity: peak blood levels came at a median of 72 hours — slow absorption, typical of a fatty-acid-modified peptide — and the terminal half-life ranged from 150.9 to 403.5 hours, or 6.3 to 16.8 days. The programme's two higher-dose cohorts (EClinicalMedicine 2022, PMID 36247927; 16 people on the compound) gave 7.3 to 44.8 days after the first dose. A US high-dose study reported about 8 days after 20 weeks at its top dose (Diabetes, Obesity and Metabolism 2025, PMID 40832785). The figures sit in the papers' full texts rather than their abstracts, which is why a search of abstracts misses them; an earlier version of this page said no half-life had been published, and that was wrong. The spread is the finding. These are small studies, and the first-dose half-life differed more than sixfold between individuals, so any single figure quoted without its study and its range is a simplification. What the record does establish is the interval, which is the practically relevant quantity anyway. Every phase 1b, phase 2 and phase 3 trial in the programme dosed once weekly, and the regulatory approval is for a once-weekly product. A dosing interval that survived four phase 3 trials, together with the measured ranges above, is a stronger statement about duration of action than any single half-life figure copied from a vendor page. If you see one specific number quoted for this compound, the useful question is which study it came from and what range that study reported.

Storage & handling

• Lyophilized (powder): store sealed and refrigerated at 2-8°C, protected from light and moisture; long-term storage is commonly at -20°C or below. Do not use past intended research shelf life.
• Reconstituted (liquid): refrigerate at 2-8°C, protect from light, and avoid freeze-thaw cycles and vigorous shaking.
• A once-weekly compound means a reconstituted vial is entered repeatedly over weeks, which is the case bacteriostatic water exists for — its benzyl alcohol is a preservative for multi-dose entry that sterile water does not provide.
• Label the vial with the reconstitution date and the resulting concentration. The concentration is the number the unit arithmetic depends on, and it is the one nobody remembers a fortnight later.

Evidence File

The Mazdutide Evidence File: Nine Chinese Trials, Two American Ones, and the Results the Registry Is Still Waiting For

Mazdutide is one of the few compounds in this library with an approval behind it — in China, in 2025 — and a phase 3 programme published in the New England Journal of Medicine, JAMA and Nature. That changes what an evidence file is for. This one audits the record rather than scraping for it: it counts the literature, separates the Chinese trials from the two run in the United States, reads the one trial that has posted its results to the registry, and lists the completed studies that have published nothing, including the head-to-head against semaglutide.

• 11 meta-analyses and reviews of pooled data against 9 trial-typed records
• 211 people randomised in the two published trials run outside China
• 1 of 47 registry records with results posted
• 20% stopped treatment for adverse events in the highest US arm

Sourcing File

The Mazdutide Sourcing File: One Registry Record, a 33-Residue Chain, and the Neighbours a Mass Spectrum Separates

Mazdutide is an approved medicine in China, but no research vial is that medicine. Everything sold under the name for research is a synthetic peptide whose identity rests on its certificate of analysis. This file anchors the compound to its public chemistry record, reads the sequence out of that record and checks it against the formula, and works out what a real mass spectrum, purity trace and peptide-content line must show — then sets out which substitutions a spectrum catches and which defects it cannot see.

• 4473.29 Da monoisotopic, rebuilt from the sequence to four decimals
• 67 Da to the nearest verified neighbour, cagrilintide
• 246 PubChem records within 95% structural similarity, semaglutide first
• 5 basic sites that set the salt arithmetic behind the label weight

Benefit & Outcome Review

The Mazdutide Benefit & Outcome Review: Weight and Glucose Proven, the Rest Still in Mice, Reviews or Unpublished Trials

Mazdutide's main claims are unusually well supported: weight loss and blood-glucose control rest on phase 3 trials that a regulator has reviewed. The claims built on top of them are a different matter. This review grades each one — weight, glucose, the semaglutide comparison, liver fat, metabolism, the brain, the heart, uric acid and what happens after stopping — against what was measured, in which species and in which population, and names the absences the searches found.

• 2 outcomes supported by published phase 3 trials
• 0 published head-to-head results against semaglutide
• 0 human measurements of energy expenditure located
• 0 cardiovascular outcome trials in the registry

Guide FAQ

Quick answers about guide scope, access, and educational use context.