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Mazdutide vs Retatrutide: Dual vs Triple Agonist Compared

Approval status varies by country

Editorially reviewed · Last updated September 8, 2026 · How we review

Mazdutide and retatrutide both include glucagon receptor agonism in their design, which sets them apart from earlier drugs like semaglutide (GLP-1 only) and tirzepatide (GLP-1 + GIP). But they are not the same drug, and they take different approaches to multi-receptor agonism.

Mazdutide is a dual agonist targeting GLP-1 and glucagon. Retatrutide is a triple agonist targeting GLP-1, GIP, and glucagon. Both have shown significant weight loss and liver fat reduction in clinical trials, but they differ in mechanism, dosing, regulatory status, and the populations studied.

This page compares the two drugs based on published trial data. No head-to-head trial between mazdutide and retatrutide has been conducted, so all comparisons are cross-trial and should be interpreted with caution.

At a glance — how do they differ?

MazdutideRetatrutide
MechanismGLP-1 + Glucagon (dual agonist)GLP-1 + GIP + Glucagon (triple agonist)
DeveloperInnovent Biologics (originally discovered by Eli Lilly)Eli Lilly
Regulatory statusApproved in China (obesity: June 2025, T2D: September 2025). Brand name: Xinermei. Not FDA approved; a completed US Phase 2 study was published in August 2026.Not approved anywhere. Phase 3 (TRIUMPH program) ongoing.
DosingOnce weekly injectionOnce weekly injection
Selected trial dose9 mg in GLORY-212 mg
Selected Phase 3 weight loss-18.55% overall (GLORY-2, 9 mg, 60 wks, efficacy estimand)-28.7% (TRIUMPH-4, 12 mg, 68 wks)
HbA1c reduction-2.03% (DREAMS-3, 6 mg)-2.02% (Phase 2)
Liver fat reductionUp to -80.2% (GLORY-1, 6 mg, baseline liver fat >=10%)86.0% relative at 48 weeks (Phase 2 substudy, 12 mg)
Tolerability comparisonRates vary by dose and studyNo direct mazdutide comparison
AvailabilityAvailable in China. Not available in the US or Europe.Investigational; no approved launch date.

How do the mechanisms differ?

Both mazdutide and retatrutide include glucagon receptor activity, which is what makes them fundamentally different from semaglutide and tirzepatide. But they diverge in which other receptor they target alongside glucagon.

Mazdutide: GLP-1 + Glucagon

Mazdutide activates two receptors: GLP-1 and glucagon. GLP-1 reduces appetite and improves insulin secretion. The glucagon component promotes fat oxidation in the liver and increases energy expenditure. Notably, mazdutide does not target GIP.

This dual approach focuses on the combination of appetite suppression (GLP-1) and increased metabolic activity (glucagon). The absence of GIP agonism distinguishes mazdutide from tirzepatide and retatrutide.

Retatrutide: GLP-1 + GIP + Glucagon

Retatrutide activates all three receptors: GLP-1, GIP, and glucagon. GIP complements GLP-1 by further enhancing insulin secretion and may have additional effects on fat metabolism. A shared receptor target does not establish equal liver-fat effects or energy expenditure in humans.

The addition of GIP defines retatrutide as a triple agonist. Glucagon receptor activation is being studied for effects on energy expenditure and hepatic fat metabolism. Preclinical studies support this rationale, but the human trials do not isolate how much weight loss each receptor contributes. Counting receptor targets cannot establish which drug is better.

The Common Thread: Glucagon

What both drugs share — and what sets them apart from semaglutide and tirzepatide — is glucagon receptor activation. This is the receptor responsible for:

  • Hepatic fat oxidation: directly breaking down fat stored in the liver
  • Thermogenesis: increasing the body's energy expenditure
  • Lipolysis: promoting fat breakdown in adipose tissue

The shared receptor target provides a research rationale, not proof that the two drugs have equivalent effects or outperform other medicines for liver disease.

How much weight loss did each show?

Mazdutide (GLORY-1 Trial)

The GLORY-1 trial was a Phase 3, randomized, double-blind, placebo-controlled study published in the New England Journal of Medicine in 2025. It enrolled 610 Chinese adults with obesity (BMI >= 28) or overweight (BMI >= 24) with at least one weight-related comorbidity (mean baseline weight 87.2 kg, mean BMI 31.1). Participants were randomized to mazdutide 4 mg, 6 mg, or placebo, once weekly for 48 weeks. Results at Week 48, reported under both the efficacy estimand (effect if treatment is taken as intended) and the treatment-policy estimand (effect regardless of adherence):
DoseWeight Loss (efficacy estimand)Weight Loss (treatment-policy)
Mazdutide 4 mg-12.05%-11.00%
Mazdutide 6 mg-14.84%-14.01%
Placebo-0.47%+0.30%
Responder rates at the 6 mg dose were high: 50.6% of participants achieved at least 15% weight loss, 67.9% achieved at least 10%, and 82.8% achieved at least 5% — versus 2.1%, 2.9%, and 11.5% on placebo. Mazdutide 6 mg also reduced waist circumference by 10.96 cm (versus 1.48 cm on placebo).
The newer GLORY-2 trial studied mazdutide 9 mg for 60 weeks in 462 Chinese adults with moderate-to-severe obesity, including people with diabetes. The efficacy-estimand reduction was 18.55% overall, versus 3.02% with placebo; the subgroup without diabetes had 20.08%, versus 2.81%. That subgroup figure is not the overall trial result. Manufacturer report.
A US Phase 2 study published in August 2026 adds evidence beyond the Chinese program. It enrolled 179 adults without diabetes and studied mazdutide doses up to 16 mg over 48 weeks. At the primary 32-week endpoint, the 16 mg group had 18.1% mean weight reduction under the efficacy estimand, versus 0.9% with placebo. This was a separate study, not a retatrutide comparison.

Retatrutide (Phase 2 and TRIUMPH-4)

Retatrutide's weight loss data comes from two key studies:

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TrialDoseDurationWeight Loss
Phase 2 (NEJM 2023)12 mg48 weeks-24.2%
TRIUMPH-4 (Phase 3)12 mg68 weeks-28.7%

TRIUMPH-4 enrolled participants with obesity and knee osteoarthritis, a specific population that may not be directly comparable to GLORY-1's general obesity cohort.

Why These Numbers Cannot Be Compared Directly

The weight loss figures above come from different trials with significant differences:

  • Population: GLORY-1 enrolled Chinese adults. Retatrutide trials enrolled primarily Western populations. Ethnic and genetic differences can affect drug response, body composition, and baseline metabolic profiles.
  • Duration: GLORY-1 was 48 weeks. TRIUMPH-4 was 68 weeks. Longer trials generally produce greater weight loss, as the weight loss curve may not have plateaued.
  • Dose and formulation: GLORY-1 studied mazdutide up to 6 mg; GLORY-2 studied 9 mg. Retatrutide trials studied up to 12 mg. Milligram doses across different molecules are not equivalent.
  • Trial phase and size: Both GLORY-1 and TRIUMPH-4 are Phase 3 trials, but they differ in sample size, inclusion criteria, and study design.
  • Comparator populations: TRIUMPH-4 specifically enrolled people with knee osteoarthritis, while GLORY-1 enrolled a broader obesity population.

These separate studies do not establish which treatment would produce greater weight loss in the same population.

How do they handle diabetes?

Mazdutide (DREAMS-3 Trial)

The DREAMS-3 trial is notable because it is a head-to-head comparison — mazdutide 6 mg versus semaglutide 1 mg in adults with type 2 diabetes over 32 weeks.

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OutcomeMazdutide 6 mgSemaglutide 1 mgP-value
Primary composite (HbA1c <7% + >=10% weight loss)48%21%p<0.0001
HbA1c reduction-2.03%-1.84%—
Weight loss-10.29%-6.00%—

This is one of the few head-to-head trials in this drug class, and it showed mazdutide outperforming semaglutide 1 mg on both glycemic control and weight loss. However, the maximum approved weekly Ozempic injection dose is 2 mg, and the trial used the 1 mg dose, not the highest available dose.

Retatrutide (Phase 2 T2D Data)

Phase 3 diabetes evidence is now available from TRANSCEND-T2D-1, which reported HbA1c reductions of 1.7–2.0 percentage points across doses at 40 weeks.
The historical retatrutide diabetes results below come from a Phase 2 trial in people with type 2 diabetes, published in The Lancet in 2023:
  • HbA1c reduction: -2.02% at the 12 mg dose
  • This was not a direct comparison with mazdutide or tirzepatide

Both drugs show strong glucose-lowering effects. The glucagon component, which raises blood sugar in isolation, is more than offset by the GLP-1 activity (and GIP activity in retatrutide's case) in both drugs, resulting in net HbA1c improvement.

How much liver fat did each clear?

Liver fat reduction is where the glucagon receptor really matters, and both mazdutide and retatrutide have produced striking data in this area.

DrugLiver Fat ReductionSource
Mazdutide 6 mg-80.2% (baseline liver fat >=10%); -73.2% (baseline >=5%)GLORY-1 Phase 3, Week 48
Mazdutide 4 mg-65.9% (baseline liver fat >=10%); -63.3% (baseline >=5%)GLORY-1 Phase 3, Week 48
Retatrutide 12 mg86.0% relative reductionPhase 2 liver substudy, 48 weeks; baseline liver fat ≥10%

The mazdutide liver results are subgroup measurements within GLORY-1. They should not be treated as a comparison with the separately enrolled retatrutide liver substudy.

The retatrutide Phase 2 liver substudy included 98 participants with baseline liver fat of at least 10%. At 12 mg, relative liver fat reduction was 82.4% at 24 weeks and 86.0% at 48 weeks. MRI-measured fat reduction does not establish MASH resolution, fibrosis improvement, or superiority over another drug.

Neither the MRI measurements nor receptor targets establish that mazdutide or retatrutide is a better treatment for MASH than existing options.

Retatrutide is included in SYNERGY-Outcomes. Outcomes and biopsy endpoints answer different questions from MRI liver-fat reduction; this page does not establish which drug is better for MASH.

How do the trial programs compare?

Mazdutide's evidence base comes from two Phase 3 program families in China — GLORY (obesity) and DREAMS (type 2 diabetes). Several of these are head-to-head designs against currently approved drugs, which is unusual in this class:

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TrialPopulationComparatorStatus
GLORY-1Overweight/obesityPlaceboMet endpoints (NEJM 2025)
GLORY-2Moderate-to-severe obesityPlaceboReported; JAMA 2026
GLORY-3Overweight/obesity + MAFLDSemaglutideOngoing
DREAMS-1Treatment-naive T2DPlaceboMet endpoints
DREAMS-2T2D on oral antidiabeticsDulaglutideMet endpoints
DREAMS-3T2D + obesitySemaglutideReported
Retatrutide does have an active-comparator Phase 3 study: TRIUMPH-5 compares it with tirzepatide. It does not compare retatrutide with mazdutide, and no results were available at this review.

Where is each approved — US vs China?

Mazdutide

Mazdutide was developed by Innovent Biologics, a Chinese biopharmaceutical company, based on a molecule originally discovered by Eli Lilly. It is approved in China under the brand name Xinermei:
  • June 2025: Approved by China's National Medical Products Administration (NMPA) for chronic weight management
  • September 2025: Approved in China for type 2 diabetes
Mazdutide is not approved by the FDA or the European Medicines Agency. A completed US Phase 2 trial was published in August 2026; an FDA approval timeline has not been established.

Retatrutide

Retatrutide is being developed by Eli Lilly and is in the Phase 3 TRIUMPH clinical trial program. It is not approved anywhere — neither in the US, Europe, nor China.
Lilly plans a US biologics license application in the first quarter of 2027. That is a filing target, not an FDA approval or launch date.

Practical Implications

If you are outside China, neither drug is available by prescription. Within China, mazdutide (Xinermei) can be prescribed for obesity or type 2 diabetes. Retatrutide is only accessible worldwide through clinical trial enrollment. For how retatrutide itself is dosed in trials, see the retatrutide dosage guide.

How do the side effects compare?

Both drugs share the gastrointestinal side effect profile common to all GLP-1-based therapies: nausea, diarrhea, vomiting, and decreased appetite, particularly during dose escalation.

Mazdutide Tolerability

GLORY-1 discontinuation results should not be generalized to every mazdutide dose or population. In the US Phase 2 study, 20% of the 16 mg group discontinued treatment because of adverse events, mainly gastrointestinal disorders. This does not establish comparative safety against retatrutide.

Retatrutide Tolerability

Dysesthesia (altered skin sensation) occurred in 8.8% and 20.9% of the retatrutide 9 mg and 12 mg groups in TRIUMPH-4. It is not unique to retatrutide: current Wegovy and Zepbound labels also report it. A glucagon-specific cause has not been established.

Whether mazdutide, which also activates the glucagon receptor, produces a similar dysesthesia signal has not been clearly reported in published data.

For more detail on retatrutide's safety profile, see Side Effects & Safety.

Frequently Asked Questions

Is mazdutide the same as retatrutide?

No. Mazdutide is a dual agonist (GLP-1 + glucagon) developed by Innovent Biologics. Retatrutide is a triple agonist (GLP-1 + GIP + glucagon) developed by Eli Lilly. They share glucagon receptor activity but differ in their additional receptor targets, dosing, and stage of development.

Which drug produces more weight loss?

The newer GLORY-2 study reported 18.55% with mazdutide 9 mg at 60 weeks overall, and 20.08% in the subgroup without diabetes, using the efficacy estimand. Retatrutide 12 mg produced 28.7% at 68 weeks in TRIUMPH-4. These are separate populations and analyses, so the difference is not a head-to-head treatment effect.

Can I get mazdutide in the US?

No. Mazdutide is only approved in China. US Phase 2 results were published in August 2026, but there is no established timeline for FDA approval. It is not available through US pharmacies or telehealth providers.

Which is better for fatty liver disease?

No direct comparison establishes that. Both have reported substantial relative liver-fat reductions, but study populations, baseline thresholds, and analyses differ. Lower MRI liver fat does not by itself establish MASH resolution, fibrosis improvement, or fewer liver complications.

Is there a connection between mazdutide and Eli Lilly?

Yes. The mazdutide molecule was originally discovered by Eli Lilly and licensed to Innovent Biologics for development in China. Eli Lilly separately developed retatrutide as its own triple agonist. The two drugs have different structures and receptor profiles despite sharing a corporate lineage.

Will there ever be a head-to-head trial?

No direct mazdutide–retatrutide study was identified in this review. Both development programs include comparisons against other drugs, including retatrutide versus tirzepatide in TRIUMPH-5. That does not answer the direct mazdutide comparison.

Does mazdutide raise heart rate like other GLP-1 drugs?

Yes, modestly. In GLORY-1, mean heart rate rose by 2.6 beats per minute at Week 48 in both the 4 mg and 6 mg groups, with no cardiovascular safety signals observed over the trial. A small heart rate increase is common across GLP-1-based therapies, including retatrutide. As with any of these drugs, a clinician should monitor it, particularly in people with existing cardiac conditions.

Sources

  • Hsia, S.H., et al. (2026). Mazdutide in US adults with obesity or overweight: Phase 2 trial. The Lancet Diabetes & Endocrinology.
  • Innovent. China approvals and DREAMS results.
  • JAMA. GLORY-2, mazdutide 9 mg.
  • Nature Medicine. Retatrutide liver substudy.
  • Lilly. Phase 3 update and filing plan.
  • Ji, L., et al. (2025). Mazdutide in Chinese Adults with Overweight or Obesity (GLORY-1). New England Journal of Medicine.
  • Innovent Biologics. (2025). Phase 3 Clinical Study of Mazdutide in Chinese Adults with Overweight or Obesity (GLORY-1) Published in NEJM. Press release — Week 48 efficacy estimand (4 mg -12.05%, 6 mg -14.84%), responder rates, waist circumference, liver fat by baseline strata, heart rate, and the GLORY/DREAMS program overview.

  • DREAMS-3 trial results. Mazdutide vs semaglutide 1 mg in type 2 diabetes. Phase 3, 32 weeks.

  • Jastreboff, A.M., et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine. DOI: 10.1056/NEJMoa2301972
  • Rosenstock, J., et al. (2023). Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-comparator-controlled, parallel-group, phase 2 trial. The Lancet. DOI: 10.1016/S0140-6736(23)01053-X
  • Eli Lilly and Company. (2025). Lilly's retatrutide achieved significant weight loss and pain relief in adults with obesity and knee osteoarthritis. Press release.
  • ClinicalTrials.gov: Mazdutide trials, Retatrutide trials
How we keep this honest
What this is
Educational information, not medical advice. It reports published research — it doesn’t recommend that you use, obtain, or supply anything.
Regulatory status
Mazdutide has NMPA approval in China for specific weight-management and type 2 diabetes indications. That approval does not establish U.S. approval. Retatrutide remains investigational.
Our standard
Every claim traces to a primary source. We label the strength of evidence and flag estimates as estimates — never as clinical fact.
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We don’t sell, supply, or link to suppliers of any medicine, and aren’t affiliated with any manufacturer.

Do not make decisions about your health without consulting a qualified healthcare provider. For trial enrolment, see ClinicalTrials.gov. More on how we review.

Sources

Grounded in primary sources
NEJMThe LancetJAMAFDAClinicalTrials.gov

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