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Mazdutide

Oxyntomodulin-based GLP-1 and glucagon dual agonist approved in China, notable for adding thermogenic energy expenditure to appetite suppression.

Also known as oxyntomodulin analogue, GLP-1/glucagon dual agonist, Xinermei, LY3305677, IBI362

Approved drug — Licensed by a major regulator for human use, with phase-3 trial data behind it.

Approved by China's NMPA in June 2025 for chronic weight management and in September 2025 for type 2 diabetes, on the GLORY and DREAMS phase 3 programmes. Approved evidence, but Chinese-population trials with lower baseline BMI than Western obesity trials - do not assume the percentages transfer directly.

How it works

Mazdutide is a lipidated analogue of oxyntomodulin, the natural proglucagon product that activates both receptors. GLP-1 receptor activation delivers the familiar appetite and glycaemic effects; glucagon receptor activation raises resting energy expenditure, drives hepatic lipolysis and reduces liver fat. Chinese phase 3 data show meaningful reductions in liver fat and uric acid alongside weight loss, and the energy-expenditure component means weight loss is less purely intake-driven than with a pure GLP-1. Mazdutide is the first GCGR/GLP-1R dual agonist approved anywhere in the world.

Targets: GLP-1 receptor, Glucagon receptor

Dosing

ProtocolDoseFrequencyRoute
Approved Chinese weight-management dosingSame day each week.4 mg – 6 mgonce weeklysubcutaneous
  • · Approved maintenance doses are 4 mg and 6 mg weekly after stepped escalation; a 9 mg supplementary application for moderate-to-severe obesity is under NMPA review.

Titration

Stepped escalation over 8-16 weeks. As with all glucagon-containing agonists, escalate slowly and watch heart rate.

Cycling

Chronic therapy, not cycled.

Work out your exact syringe units →

Pharmacology

Half-life
Supports once-weekly dosing.
Onset
Appetite reduction in the first weeks; weight loss continued through 48 weeks in phase 3.
Routes
subcutaneous
Molecule
Acylated oxyntomodulin analogue with GLP-1 and glucagon receptor activity

Handling

Diluent
Not applicable for the approved pen; bacteriostatic water for research-grade powder
Typical mix
1 or 2 mL
Lyophilised
Refrigerate at 2-8 C.
Reconstituted
Refrigerated, use within about 28 days.
Light sensitive
Yes — keep it out of the light

Side effects

  • very commonNausea
  • commonDiarrhoea
  • commonIncreased heart rate— Glucagon-receptor effect.
  • uncommonTransient rise in liver enzymes— Reported in some Chinese trial data; generally resolves.

Do not use if

  • Personal or family history of medullary thyroid carcinoma or MEN2 - class effect.
  • History of pancreatitis.
  • Pregnancy.
  • Uncontrolled tachyarrhythmia.

Combining it

  • redundantsemaglutide — GLP-1 agonism already present.
  • redundantsurvodutide — Same dual-receptor mechanism.
  • cautioninsulin-analogues — Mixed glucose effects from the two receptor arms; monitor closely.

What to monitor

  • · Weight.
  • · Heart rate.
  • · Liver enzymes.
  • · HbA1c and uric acid.

Legal status

Approved in China; investigational in the US and EU.

References

  • Mazdutide: First Approval, Drugs 2025 (review)
  • GLORY-1 phase 3 trial of mazdutide in Chinese adults with obesity (trial)
  • DREAMS phase 3 programme in type 2 diabetes (trial)

Mechanism in depth

Mazdutide is an engineered oxyntomodulin analogue, which is a neat piece of pharmacological history: oxyntomodulin is the endogenous proglucagon-derived peptide that naturally hits both the GLP-1 and glucagon receptors, and mazdutide is essentially what you get if you take that natural dual agonist and give it a week-long half-life. The glucagon arm adds thermogenesis and hepatic fat oxidation on top of GLP-1-driven appetite suppression, and in the Chinese phase 3 programme it produced meaningful weight loss alongside HbA1c reductions that beat dulaglutide head-to-head. The distinguishing clinical observation from the Chinese trials is a reduction in liver fat and in uric acid that is larger than weight loss alone predicts, consistent with the glucagon arm doing hepatic work. The important caveat for a Western reader is population: GLORY-1 and the DREAMS diabetes trials enrolled Chinese adults with substantially lower baseline BMI than Western obesity trials, and percentage weight loss in a lower-BMI population is not directly comparable to SURMOUNT or STEP figures. It also means the absolute kilogram losses are smaller than the percentages suggest. Mazdutide is approved in China for both weight management and type 2 diabetes and is investigational elsewhere.

What usually goes wrong

The main error for a Western reader is transferring the percentages. GLORY-1 enrolled a population with a much lower baseline BMI than SURMOUNT or STEP, and percentage weight loss in that setting does not translate. The second is the usual glucagon-arm issues - heart rate and early fasting glucose - compressed by fast escalation. Third, mazdutide is approved only in China, so material sold elsewhere is unregulated.

Titration ladder

  1. 3 mgEscalation — The Chinese obesity phase 3 studied 4 mg and 6 mg maintenance doses with stepwise escalation; a 9 mg dose has been studied in a separate phase 2. Exact step durations were not verified here.
  2. 4 mgMaintenance — Lower approved maintenance dose in the Chinese obesity indication.
  3. 6 mgMaintenance — Higher approved maintenance dose.
  4. 9 mgInvestigational — Studied in a phase 2 trial in Chinese adults with BMI at or above 30; not an approved dose.

Bloodwork worth running

MarkerWhenWhy it matters
Fasting glucose and HbA1cBaseline, then monthly through escalation, then 3-monthly.The glucagon arm can push glucose up early; the GLP-1 arm and weight loss pull it down over months. In the Chinese phase 3 the net effect beat dulaglutide.Act if: A sustained rise in fasting glucose during escalation means hold rather than climb.
Resting heart rateDaily during escalation.Any glucagon receptor agonist raises it.Act if: More than 15 bpm above baseline means stop escalating.
ALT, AST and uric acidBaseline and 6 months.Both fall more than weight loss alone would predict, which is the glucagon arm's fingerprint.Act if: None; these are the markers that show the mechanism working.
Body composition by DEXABaseline and every 3-4 months.Same as every effective weight drug.Act if: No established threshold.

Pharmacokinetics

Crosses blood-brain barrier
partial
Accumulates
Yes — doses stack before steady state
Metabolism
Presumed proteolytic backbone cleavage plus beta-oxidation of the acyl chain.
Elimination
Presumed catabolic.

Receptor targets

  • GLP-1 receptor (GLP1R) — Not verified

    Appetite suppression, delayed gastric emptying, glucose-dependent insulin secretion, glucagon suppression.

  • Glucagon receptor (GCGR) — Not verified

    Increased energy expenditure, hepatic fat oxidation, and the reductions in liver fat and uric acid that exceed what weight loss alone explains. Also raises heart rate modestly.

Trials

  • GLORY-1 Phase 3 · n=610 · 48 weeks · 2025

    Once-weekly mazdutide produced significant weight reduction versus placebo in Chinese adults with obesity or overweight.

  • Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes Phase 3 · 2026

    HbA1c reduction superior to dulaglutide.

  • Mazdutide versus placebo in Chinese adults with type 2 diabetes Phase 3 · 2026

    HbA1c reduction versus placebo.

  • Mazdutide 9 mg phase 2 Phase 2 · 2026

    Weight reduction at 9 mg weekly in Chinese adults with a BMI of 30 or above without diabetes.

What to expect, and when

Appetite reduction in the first weeks; weight loss continued through 48 weeks in phase 3. Liver fat and uric acid fall earlier than weight would predict.

Stacking and comparisons

Redundant with every GLP-1 agonist and with every other glucagon-containing dual or triple agonist. In the Chinese trials the background therapy was metformin, which is the sensible pairing. There is no published combination work with amylin analogues. Outside China there is no legitimate supply.

Against ecnoglutide, the other Chinese-approved entrant: mazdutide has the stronger evidence package, including NEJM and Nature phase 3 publications and a head-to-head win over dulaglutide. Against survodutide: the same GLP-1-plus-glucagon concept; survodutide has the biopsy-confirmed fibrosis data and larger Western trials, mazdutide has an actual approval. Against tirzepatide and semaglutide: not directly comparable because of population differences, and neither has been tested head-to-head against mazdutide.

Rough cost

Chinese domestic pricing only; no Western retail channel exists. Not verified.

Genuinely uncertain

  • No verifiable human pharmacokinetic parameters.
  • Titration step durations and the exact approved escalation schedule in China were not verified.
  • Percentage weight-loss figures come from a lower-BMI population and are not directly comparable to Western obesity trials.
  • Receptor affinities and the GCGR-to-GLP1R ratio are not published in verifiable form.
  • The 610-participant figure for GLORY-1 was not individually re-verified against the paper.

Papers