Mazdutide

IBI362 / LY3305677

Mazdutide (IBI362 / LY3305677) is a metabolic & fat loss research compound. Dual GLP-1/glucagon receptor agonist — incretin appetite control plus glucagon-driven energy expenditure and hepatic fat reduction.

How Mazdutide works

Dual GLP-1/glucagon receptor agonist — incretin appetite control plus glucagon-driven energy expenditure and hepatic fat reduction.

Proposed benefits

Researched for fat oxidation, appetite and energy regulation, insulin sensitivity and endurance capacity.

Where to get Mazdutide

The evidence for Mazdutide

Graded by what exists behind each claim.

✅ Clinically validated

• Approved in China in 2025 and in late-stage trials elsewhere. A GLP-1/glucagon dual agonist licensed from Eli Lilly by Innovent, with phase 3 data in Chinese populations showing substantial weight loss.
• The population matters when reading the numbers: the pivotal trials were run largely in Chinese participants at lower baseline BMI than Western obesity trials, so percentage results are not directly comparable to tirzepatide's.

📊 Correlative data

• Real-world use is essentially confined to China and very recent. Trial reports note the class-typical GI profile plus increased heart rate, which is the glucagon arm showing up.

🧪 Theoretical / extrapolated

• Based on oxyntomodulin, a naturally occurring gut hormone that intrinsically hits both GLP-1 and glucagon receptors — so this is a biomimetic design rather than an engineered chimera.
• Same dual logic as survodutide: GLP-1 suppresses intake, glucagon raises expenditure and mobilizes liver fat. Trials have also reported reductions in hepatic fat and uric acid consistent with the glucagon component.

How to read these tiers: they say how much human evidence exists, not how well something works — and ✗ flags harm, never a disappointing trial. How the evidence tiers work →

What Mazdutide actually does

Mazdutide is a GLP-1 and glucagon receptor dual agonist built on an oxyntomodulin backbone, and the ratio between its two arms is not published anywhere. Five registered-trial publications — a phase 1b, two phase 2s and two phase 3s Ji 2022 Zhang 2023 Ji 2023 Ji 2025 Gao 2026 — and not one prints a receptor potency ratio. For a molecule whose entire difference from semaglutide is the second receptor, that is the missing number.

So derive it from the clinical data instead, which nobody does. The phase 2 in type 2 diabetes ran mazdutide against open-label dulaglutide in the same trial, which makes it the cleanest natural experiment in this cohort Zhang 2023. Over 20 weeks: HbA1c fell 1.41% to 1.67% on mazdutide and 1.35% on dulaglutide — essentially the same. Body weight fell up to 7.1% on mazdutide and 2.7% on dulaglutide — more than double. Read those two lines together and the ratio falls out: mazdutide’s GLP-1 arm is doing roughly what a conventional weekly GLP-1 does for glucose, while something else is producing 2.6 times the weight loss. That something else is the glucagon receptor, and this is the closest thing to a measured contribution the published record contains.

What the glucagon arm buys. Glucagon receptor agonism raises energy expenditure and drives hepatic fat oxidation — the liver burns its own stored triglyceride rather than exporting it. Appetite suppression works on the intake side of the equation; this works on the output side, which is why a dual can exceed the ceiling a pure GLP-1 hits.

What it costs, and the cost is visible in the same trial. Hypoglycemia was reported in 10% of mazdutide-treated participants against 8% on placebo Zhang 2023. That two-point gap is small and it is the right place to look: glucagon raises hepatic glucose output, so an unopposed glucagon arm should reduce hypoglycemia risk, not raise it. It rose slightly, which says the GLP-1 arm dominates glycemic control at these doses. That is a mechanistic inference from a safety table, and it is more informative about the ratio than anything on the product page.

The design origin, stated accurately. Mazdutide is based on oxyntomodulin, a naturally occurring 37-residue gut hormone produced from the same proglucagon precursor as GLP-1 and glucagon, which intrinsically activates both receptors. So this is not a chimera assembled from two drugs; it is a natural dual agonist given the half-life engineering it lacks. Native oxyntomodulin is cleared in minutes; the marketed molecule is once-weekly, and the general solution for that in this class is reversible albumin binding through a fatty acid side chain Muller 2022.

The names, which are not decoration. IBI362 and LY3305677 are the same molecule Ji 2022: it was discovered at Eli Lilly and licensed to Innovent for China. That is why the entire trial program is Chinese, and it is why comparing these percentages to Western obesity-trial percentages is not straightforward — the phase 3 population had a mean baseline weight of 87.2 kg and a BMI of 31.1 Ji 2025, where Western obesity trials commonly start above 100 kg.

Cell, rodent, human — and where it stops

Step one, phase 1b, and the anomaly is in the first experiment. 24 participants at five Chinese hospitals, randomized 2:1 within each cohort (NCT04440345). The 9 mg cohort escalated 3→6→9 mg over 12 weeks; the 10 mg cohort escalated 2.5→5→7.5→10 mg over 16 weeks. Weight change: −11.7% at 12 weeks in the 9 mg cohort against −1.8% on placebo (estimated treatment difference −9.8%, 95% CI −14.4 to −5.3, P = 0.0002), and −9.5% at 16 weeks in the 10 mg cohort against −3.3% (difference −6.2%, 95% CI −11.5 to −0.9, P = 0.024) Ji 2022. A higher dose, given for four more weeks, produced less weight loss. Before reading anything into that: each arm held eight people on drug and four on placebo, and one drug participant and two placebo participants in the 10 mg cohort withdrew. That is noise, and it is worth showing rather than smoothing, because the same non-monotonic shape appears in the dual-agonist next to it in this catalog Harrison 2024 and somebody should eventually find out whether it is always noise.

Step two, phase 2 in type 2 diabetes, with an active comparator. Mazdutide 3 mg (n = 51), 4.5 mg (n = 49) or 6 mg (n = 49) against open-label dulaglutide 1.5 mg (n = 50) and placebo (n = 51), 20 weeks. HbA1c −1.41% to −1.67% versus −1.35% and +0.03%, all P < 0.0001 against placebo; weight up to −7.1% versus −2.7% and −1.4%. Adverse events: diarrhea 36%, decreased appetite 29%, nausea 23%, vomiting 14%, hypoglycemia 10% against 8% on placebo Zhang 2023.

Step three, phase 2 in obesity. 248 participants at 20 Chinese hospitals, 24 weeks (NCT04904913). Weight change −6.7% (3 mg), −10.4% (4.5 mg) and −11.3% (6 mg) against +1.0% on placebo, treatment differences −7.7% to −12.3%, all p < 0.0001 Ji 2023.

Step four, phase 3 GLORY-1. 610 participants, 4 mg or 6 mg or placebo, 48 weeks (NCT05607680). At week 32: −10.09% (95% CI −11.15 to −9.04) at 4 mg and −12.55% (−13.64 to −11.45) at 6 mg against +0.45% on placebo, with 73.9%, 82.0% and 10.5% losing at least 5%. At week 48: −11.00% and −14.01% against +0.30%, with 35.7%, 49.5% and 2.0% losing at least 15%. Discontinuation for adverse events was 1.5%, 0.5% and 1.0% Ji 2025.

Step five, phase 3 GLORY-2, which is the dose the site does not list. 27 hospitals, December 2023 to November 2025, 461 treated (307 on drug, 154 on placebo), randomized 2:1 to 9 mg weekly for 60 weeks (NCT06164873). Mean age 33.9 years, 64.0% female, 16.1% with type 2 diabetes, mean weight 94.0 kg, BMI 34.3. At week 60: −16.65% (95% CI −18.19 to −15.12) against −1.50% (−3.43 to 0.43), between-group difference −15.15% (−17.22 to −13.09), P < .001; 84.3% lost at least 5% against 33.1% Gao 2026.

And here is the trade, in one comparison the two phase 3s make possible. Going from 6 mg for 48 weeks Ji 2025 to 9 mg for 60 weeks Gao 2026 buys about 2.6 more percentage points of weight loss — and costs vomiting in 53.1% of participants against 1.3% on placebo, nausea 46.9% against 3.2%, diarrhea 39.4% against 6.5%, with discontinuation for adverse events rising from 0.5% to 2.9%. Half the people on 9 mg vomited. That is the dose the research market sells and the number nobody prints next to it.

The obstacles, named one at a time. (1) Every trial is Chinese-population, at lower baseline weight and BMI than Western obesity trials Ji 2025, so the percentages are not directly transferable in either direction. (2) No receptor ratio is published in any of the five papers, so the glucagon contribution is inferred rather than measured. (3) No head-to-head against semaglutide or tirzepatide; the only active comparator ever used is dulaglutide Zhang 2023. (4) No published body composition, so the energy-expenditure argument for a glucagon arm has never been checked against a scan. (5) No cardiovascular outcome trial. (6) The 9 mg phase 3 population had a mean age of 33.9 Gao 2026; tolerability at 9 mg in a 60-year-old is not in the record.

Mazdutide pharmacokinetics — how much of it actually gets in

The catalog says ‘~Weekly dosing’. That is a schedule, not a half-life, and no mazdutide half-life appears in any of the five published trials Ji 2022 Zhang 2023 Ji 2023 Ji 2025 Gao 2026. What follows is the bound the trial designs themselves impose.

What the escalation schedules tell you. The phase 1b stepped the dose every four weeks — 3, 6, then 9 mg — and the phase 3s ran fixed doses to week 32 and week 60 Ji 2022 Ji 2025 Gao 2026. Four weeks is the standard interval for letting a once-weekly peptide reach steady state before judging it, which places the half-life in the same neighborhood as every other weekly incretin: roughly 5 to 7 days. The one measured anchor in this cohort is ecnoglutide’s 124 to 138 hours Guo 2023. Two practical consequences: the first three weeks of use are sub-steady-state and under-represent the drug, and stopping leaves measurable exposure for three to four weeks afterwards.

What holds it in the body. Native oxyntomodulin is cleared in minutes. A weekly analog of it must carry a fatty acid that binds albumin reversibly, putting most of the dose into a circulating reservoir too large for glomerular filtration and shielded from peptidases, with the free fraction replenished continuously Muller 2022.

What degrades it. Proteolysis of the free fraction by plasma and tissue peptidases, plus renal handling of whatever is unbound; dipeptidyl peptidase-4 cleaves the proglucagon-family N-terminus unless that position is protected, which is the standard modification in this class Guo 2023. It is not a cytochrome substrate, so the interaction that matters is not metabolic — it is delayed gastric emptying changing how fast oral drugs are absorbed.

The oral barrier. Absolute. Gastric acid, pancreatic proteases, brush-border peptidases and hepatic first-pass extraction behind them. Every dose in every trial was injected.

The injectable comparator, and a card error worth naming. Every published mazdutide dose was subcutaneous, once weekly, from 2.5 mg through 10 mg Ji 2022 Gao 2026. This site’s card carries ‘1x Daily’ in its frequency field alongside ‘1-2x Weekly (Split Dose)’. There has never been a daily-dosing trial of mazdutide, and splitting a weekly dose of a 5-to-7-day peptide into two injections changes peak-to-trough with no published evidence behind it either way.

What would have to be true, and how you would know it was not

Four predictions. The first is the glucagon arm’s signature, the second is its cost, and the third is the one that would settle a claim this site currently repeats without a source.

1. Resting heart rate should rise, and it is the free readout for whether the second receptor is engaged. Heart-rate elevation is a measured class effect of incretin agonism across meta-analysis Yang 2023, and glucagon receptor agonism adds to it. Take a seated morning pulse before caffeine for a week before starting and weekly after. A person losing 12% of their body weight with a completely flat resting pulse is a person whose vial probably has no glucagon arm — which, for a research-market purchase, is the cheapest identity check available.

2. Uric acid should fall, and this is a claim that needs checking rather than repeating. The site’s own card states that trials reported reductions in hepatic fat and uric acid. The published abstracts report ‘beneficial effects on all prespecified cardiometabolic measures’ Ji 2025 without naming them, so the uric-acid claim is not verifiable from the abstract record. It is also mechanistically plausible: glucagon receptor agonism increases hepatic fatty-acid oxidation, and hepatic de novo lipogenesis and urate production share a fructose-driven ATP-depletion step. Draw uric acid at baseline and 24 weeks. This is a testable, falsifiable version of a marketing sentence, and it costs about the same as one week of the drug.

3. HbA1c and fasting insulin should both fall, and the glucose direction is the ratio test. In the phase 2, HbA1c fell as much on mazdutide as on dulaglutide Zhang 2023, which says the GLP-1 arm dominates glycemia at 3–6 mg. At 9 mg the glucagon arm is proportionally larger and nobody has published glycemic data at that dose in people without diabetes. Draw HbA1c and fasting insulin at baseline, 12 and 24 weeks. Weight falling with fasting glucose rising is the specific signature of a glucagon arm outrunning its GLP-1 counterweight.

4. Lean mass will not be spared, and at 9 mg the arithmetic is uncomfortable. More than 25% of total weight lost through pharmacotherapy comes from fat-free mass Stefanakis 2024, and no mazdutide trial reports body composition. At GLORY-2’s −16.65% Gao 2026, that is roughly 4% of starting body weight as fat-free mass — about 3.8 kg in a 94 kg person. Measure grip strength at baseline, 12, 24 and 48 weeks. The energy-expenditure argument for a glucagon arm predicts a better fat-to-lean ratio than a pure GLP-1; that prediction has never been tested, and grip strength is how one person tests it.

What nobody has tested yet

Four experiments, and the first one is the number the whole class is missing.

1. Nobody has published the receptor ratio. Five registered trials Ji 2022 Zhang 2023 Ji 2023 Ji 2025 Gao 2026 and no potency ratio in any of them. Everything on this page about ‘the glucagon arm’ is inferred from clinical contrasts — a matched HbA1c and a doubled weight loss against dulaglutide Zhang 2023 — rather than measured at a receptor. A single published cAMP potency panel would let mazdutide, pemvidutide and survodutide be compared on the one axis that actually differentiates them, and it would take a competent pharmacology lab a week.

2. Nobody has run 6 mg against 9 mg inside one trial. The comparison on this page is between two separate phase 3s with different durations, different populations and different placebo responses Ji 2025 Gao 2026. A within-trial 6-versus-9 mg arm with a prespecified tolerability endpoint would tell a buyer whether 2.6 percentage points of weight is worth a 53% vomiting rate. That is the single most decision-relevant unrun experiment for anyone actually using this compound.

3. Nobody has tested daily or split dosing. Zero trials. The frequency instructions circulating for this compound — including on this site’s own card — are inventions. Splitting a weekly dose into two halves lowers peak concentration and raises trough, which could reduce peak-driven nausea without losing efficacy, or could simply deliver less drug at the receptor when it matters. Both are plausible; neither has been measured; and this is a genuinely good experiment somebody could run with two arms of thirty people.

4. Whether the hepatic effect survives weight-matching. No mazdutide trial has compared the drug against a diet arm producing the same weight loss, so the split between glucagon-driven hepatic fat oxidation and ordinary consequence-of-weight-loss is unmeasured. The dual agonist beside it in this catalog makes the case look strong — 75.2% liver fat reduction against 6.2% weight loss Harrison 2024 is a very steep ratio — but that is a different molecule with a different and also unpublished ratio.

Mazdutide — its own safety story, not its class's

The class block on this page is written for GLP-1 receptor agonists. Four things here are specific to a glucagon-containing dual at Chinese phase 3 doses, and one of them is a number nobody quotes.

1. At 9 mg, half the participants vomited. GLORY-2 reported vomiting in 53.1% of the mazdutide group against 1.3% on placebo, nausea 46.9% against 3.2%, and diarrhea 39.4% against 6.5%, with discontinuation for adverse events at 2.9% against 0% Gao 2026. Most were mild to moderate. Compare 6 mg over 48 weeks, where discontinuation was 0.5% Ji 2025. The tolerability difference between the two doses is much larger than the efficacy difference, and the research market sells the 9 mg dose.

2. Heart rate is the glucagon-specific risk. Incretin agonism raises heart rate as a measured, meta-analyzed class effect Yang 2023; adding a glucagon receptor adds to it. None of the five trial abstracts reports the size of the heart-rate change for this molecule, which means the compound’s most predictable cardiovascular effect is not in its public record.

3. Hypoglycemia, which was reported and is worth reading correctly. 10% on mazdutide against 8% on placebo in the diabetes phase 2, in people on diet and exercise or stable metformin Zhang 2023. That is a small excess and it appeared despite a glucagon arm that should push glucose the other way. In anyone taking insulin or a sulfonylurea — populations that trial excluded — the background agent is what needs adjusting, and the risk arrives during escalation rather than at steady state.

4. Gallbladder disease, sized. Across 76 randomized trials and 103,371 patients, GLP-1 receptor agonist use carried a relative risk of gallbladder or biliary disease of 1.37 (95% CI 1.23–1.52), with a much larger signal in weight-loss trials (2.29, 1.64–3.18) and higher risk at higher doses and longer duration He 2022. A 9 mg dose run for 60 weeks Gao 2026 is at the top of every one of those multipliers. Right upper quadrant pain after meals is the symptom.

5. The honest limit of the record. The published mazdutide safety database is roughly 1,300 people across five trials Ji 2022 Zhang 2023 Ji 2023 Ji 2025 Gao 2026, almost all of them Chinese, the longest exposure 60 weeks, mean age in the pivotal 9 mg trial 33.9 years. There is no cardiovascular outcome trial and no data in older adults at the high dose. Approval in one country is not the same evidentiary position as a decade of outcome data, and this compound has the former.

Sources read for this page

• Ji L, et al. 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 2022 · PMID 36247927
• Zhang B, et al. Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial. Diabetes Care 2023 · PMID 37943529
• Ji L, et al. A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity. Nature Communications 2023 · PMID 38092790
• Ji L, et al. Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight. New England Journal of Medicine 2025 · PMID 40421736
• Gao L, 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
• Harrison SA, et al. Effect of pemvidutide, a GLP-1/glucagon dual receptor agonist, on MASLD: A randomized, double-blind, placebo-controlled study. Journal of Hepatology 2024 · PMID 39002641
• Guo W, et al. Discovery of ecnoglutide - a novel, long-acting, cAMP-biased glucagon-like peptide-1 (GLP-1) analog. Molecular Metabolism 2023 · PMID 37364710
• Yang Y, et al. Impact of a dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist tirzepatide on heart rate among patients with type 2 diabetes: A systematic review and pairwise and network meta-analysis. Diabetes, Obesity and Metabolism 2023 · PMID 37860884
• He L, et al. Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases: A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Internal Medicine 2022 · PMID 35344001
• Stefanakis K, et al. The impact of weight loss on fat-free mass, muscle, bone and hematopoiesis health: Implications for emerging pharmacotherapies aiming at fat reduction and lean mass preservation. Metabolism 2024 · PMID 39481534
• Muller TD, et al. Anti-obesity drug discovery: advances and challenges. Nature Reviews Drug Discovery 2022 · PMID 34815532

Mazdutide — safety, predicted from mechanism

Mazdutide — interference & stacking

Bloodwork to run alongside Mazdutide

Baseline first, then again at 8–12 weeks.

The “On a GLP-1 (Semaglutide / Tirzepatide)” panel covers these in one order — 11 markers, $148.05 with the discount applied.

Check results you already have → · All 103 markers A–Z

Mazdutide — frequently asked questions

What Mazdutide is used for

Mazdutide appears under 2 goals in the goal router.

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