Mazdutide

IBI362, LY3305677, OXM3; Chinese brand name 信尔美 (Xinermei) †

Metabolic & weight

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Note on this profile. Mazdutide was approved as a prescription medicine in China in 2025 for weight management † and is investigational everywhere else. This page explains the published science. Grey-market versions circulate outside China and carry the risks discussed below.

Summary

Class: Dual GLP-1 and glucagon receptor agonist; a synthetic analogue of the gut hormone oxyntomodulin with a fatty-acid side chain for once-weekly dosing
Mechanism: GLP-1 activity lowers appetite and glucose; added glucagon-receptor activity raises energy expenditure and drives liver fat breakdown
Routes studied: Subcutaneous once weekly
Dose range reported: Phase 3 (GLORY-1): titrated to 4 mg or 6 mg weekly; a 9 mg dose is in phase 3 (GLORY-2) and was used in phase 2. China approval covers 4 mg and 6 mg †. Community-reported use mirrors trial titrations but has no validated basis
Half-life: Supports once-weekly dosing (several days); exact published figure †
Storage: Approved pens: refrigerate per label. Lyophilised grey-market vials: refrigerate, protect from light, use reconstituted solution within ~4 weeks (community practice)
Regulatory status: Approved in China (NMPA, 2025) for overweight/obesity †; investigational elsewhere

Doses are as reported in studies or by the community — never recommendations.

1What it is

Mazdutide is a synthetic version of oxyntomodulin, a natural gut hormone released after meals that happens to activate both the GLP-1 receptor and the glucagon receptor. Natural oxyntomodulin lasts minutes; mazdutide is modified with a fatty-acid chain so it binds albumin and lasts a week. It was discovered by Eli Lilly (as LY3305677 / OXM3) and licensed in 2019 to Innovent Biologics for development in China, where almost all the clinical work has happened.

The glucagon-receptor component is the interesting part. Glucagon on its own raises blood glucose, which sounds unhelpful for a metabolic drug, but it also increases energy expenditure, breaks down liver fat and suppresses appetite. Balancing the two receptors so the GLP-1 effect cancels the glucose rise while the glucagon effect adds fat loss is the design idea behind mazdutide, survodutide and (with a third receptor) retatrutide. Mazdutide is the first of the dual GLP-1/glucagon to reach approval anywhere.

2How it's thought to work

GLP-1 receptor. glucose-dependent insulin release, glucagon suppression, slowed gastric emptying and reduced appetite — the familiar GLP-1 profile.

Glucagon receptor. increased resting energy expenditure, increased liver fat oxidation and lipolysis, which is why liver-fat and waist reductions in trials are large relative to the weight loss.

Net glucose effect. in trials the GLP-1 component dominated, so HbA1c fell despite glucagon activity.

Heart rate. both receptors tend to raise heart rate, and increases of several beats per minute were seen.

A single molecule activating both the GLP-1 and the glucagon receptor. GLP-1 reduces appetite and raises insulin; glucagon raises energy expenditure, which is the second arrow in the figure.Schematic — not to scale

3What the research shows

Weight loss in Chinese adults with overweight or obesity

GLORY-1 (n=610, BMI ≥28, or ≥24 with a weight-related condition, no diabetes) randomised participants to 4 mg, 6 mg or placebo weekly for 48 weeks. At week 32 (the primary endpoint) mean weight change was −10.1% (4 mg) and −12.6% (6 mg) vs +0.5% placebo; at week 48 it was about −11.0% and −14.0% vs +0.3% (Ji 2025, NEJM). Waist, blood pressure, lipids, uric acid and liver enzymes also improved. These figures sit between semaglutide 2.4 mg and tirzepatide in magnitude, though in a different population and not head-to-head. [1]

Type 2 diabetes

Two phase 3 trials, DREAMS-1 (vs placebo) and DREAMS-2 (vs dulaglutide 1.5 mg), reported in 2024–2025 that mazdutide 4 mg and 6 mg lowered HbA1c by roughly 1.4–2.0 percentage points with meaningful weight loss, superior to dulaglutide on both measures †. A diabetes indication was filed in China †.

Graded A/B

Higher dose and liver fat

Phase 2 work in Chinese adults with obesity at 9 mg showed about 15–18% weight loss at 24–48 weeks in a small cohort and reductions in liver fat content of around 70–80% in people with raised liver fat (Ji 2023, eClinicalMedicine; later dose-escalation cohort). GLORY-2 (9 mg, phase 3) is ongoing †. A head-to-head phase 3 against semaglutide 2.4 mg in people with obesity and diabetes (GLORY-3 or DREAMS-3 †) has been announced. [2][3]

Non-Chinese populations

No completed trials outside China have been published. Lilly has not pursued the molecule in Western markets, having prioritised tirzepatide and retatrutide. Whether the effect size generalises is unknown.

4Reported side effects and interactions

Literature-reported

Literature (common). nausea, diarrhoea, vomiting, constipation and decreased appetite, mostly mild to moderate and during titration; dizziness and headache; increased heart rate of roughly 4–7 bpm. Discontinuation for adverse events was low in GLORY-1 (low single-digit percentages).

Serious / theoretical. class GLP-1 cautions (pancreatitis, gallbladder disease, rodent thyroid C-cell findings — mazdutide carries the same precaution class) apply. Glucagon-receptor activity raises specific questions: a transient rise in liver enzymes in some participants, heart-rate increase, and the theoretical risk of hyperglycaemia if GLP-1 effect is lost (e.g. with antibodies). Long-term cardiovascular outcome data do not exist. Not for pregnancy.

Community-reported

Community-reported (grey-market vials outside China). nausea and fatigue similar to other GLP-1 agents; reports of faster "visceral" fat loss are unverifiable. Dosing errors from micrograms-vs-milligrams confusion and uncertain product identity are the practical risks.

Interactions. hypoglycaemia with insulin or sulfonylureas; slowed absorption of oral medicines.

Markers researchers commonly monitor

Based on the trial protocols and the dual mechanism:

Marker	Why it's watched
HbA1c and fasting glucose	the GLP-1 effect should dominate; a rising fasting glucose would be the first sign of glucagon activity outweighing it.
Liver enzymes (ALT, AST)	glucagon-receptor agonists cause transient rises in some people; also tracks the liver-fat benefit.
Resting heart rate and blood pressure	heart rate increases were larger than with pure GLP-1 agonists.
Lipid panel and uric acid	both improved in GLORY-1; useful metabolic tracking.
eGFR and creatinine	dehydration risk during GI side effects.
Body composition (DEXA or bioimpedance)	lean-mass loss has not been well characterised for this molecule; worth tracking.
Lipase/amylase	only if abdominal pain occurs.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

The approved Chinese product is a pre-filled pen. Grey-market material is sold as powder, commonly in 5 mg or 10 mg vials. Doses in trials are in milligrams (4, 6, 9 mg weekly) and titrated upward over months; the concentration after matters, and the calculator should be used to avoid unit errors. Reconstitute with , swirl gently, refrigerate.

Open in calculator, pre-loaded →

6Commonly studied alongside

Not studied in combination with other peptides. Related compounds for context: survodutide (another GLP-1/glucagon dual agonist, Boehringer Ingelheim/Zealand), retatrutide (GLP-1/GIP/glucagon triple agonist), tirzepatide, semaglutide (planned comparator), dulaglutide (comparator in DREAMS-2).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Not FDA-approved; no US trials registered by the originator †. Not permitted for compounding
European Union	Not authorised; no EMA filing
United Kingdom	Not licensed
Australia	Not approved
South Africa	Not registered
China	NMPA approved mid-2025 for long-term weight management in adults with obesity or overweight with comorbidities †; diabetes filing under review †
Sport	Not specifically prohibited by WADA; GLP-1 agonists are not listed as of 2026 †. As a non-approved substance outside China, the S0 clause could in principle apply †

8Open questions

Does the effect size seen in Chinese trial populations (lower BMI thresholds, different body composition) translate to other populations?
Long-term cardiovascular and safety outcomes — no outcome trial has reported.
How mazdutide compares head-to-head with tirzepatide and semaglutide.
Whether the glucagon component protects lean mass or improves the quality of weight loss, as sometimes claimed.

9References

1Ji L et al. (2025). Once-weekly mazdutide in Chinese adults with obesity or overweight (GLORY-1). NEJM. PubMed · DOI
2Ji L et al. (2023). A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity. Nat Commun [verify journal]. PubMed · DOI
3Ji L et al. (2023). Safety and efficacy of a GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity: a randomised, placebo-controlled, multiple-ascending-dose phase 1b trial. eClinicalMedicine. PubMed · DOI
4Zhang B et al. (2024). Efficacy and safety of mazdutide in Chinese patients with type 2 diabetes (DREAMS-1 / DREAMS-2 reports). [verify authors and journal]. PubMed
5Coskun T et al. (2022). LY3305677 / mazdutide preclinical pharmacology and glucagon/GLP-1 balance. [verify]. PubMed
6Innovent Biologics. Mazdutide prescribing information (China, 2025) [verify]. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

26 Oct 2026Profile published — awaiting medical review

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