Editorially reviewed · Last updated September 8, 2026 · How we review
Part of Weight Loss Drug Comparison Index.
Mazdutide vs Tirzepatide: GLP-1/Glucagon vs GLP-1/GIP Compared
The available GLORY and SURMOUNT results come from different trials. They do not establish that mazdutide is better for liver disease or that tirzepatide would produce more weight loss in the same patients. Innovent reported an ongoing high-dose mazdutide-versus-tirzepatide study in June 2026, but the cited update did not provide results.
Side-by-Side Comparison
| Mazdutide | Tirzepatide | |
|---|---|---|
| Developer | Innovent; molecule licensed from Lilly | Eli Lilly |
| Receptors | GLP-1 and glucagon | GLP-1 and GIP |
| Selected Phase 3 weight result | GLORY-2: −16.65% at 60 weeks, 9 mg, treatment-policy analysis | SURMOUNT-1: −20.9% at 72 weeks, 15 mg, treatment-regimen analysis |
| Study population | Chinese adults with obesity, including participants with diabetes | Adults with obesity or overweight and a complication, without diabetes |
| U.S. approval | Not FDA-approved | Mounjaro for type 2 diabetes; Zepbound for weight management and eligible adults with OSA |
| Administration | Once-weekly subcutaneous injection | Once-weekly subcutaneous injection |
The study percentages are not a head-to-head comparison. Different molecules also mean different milligram doses cannot be treated as equivalents.
How the Mechanisms Differ
Both drugs share GLP-1 receptor activity, which helps regulate appetite and glucose-dependent insulin secretion.
Tirzepatide: GLP-1 + GIP
Tirzepatide also activates GIP receptors. Its label describes reduced calorie intake, increased insulin secretion and reduced glucagon secretion in a glucose-dependent manner. Human trials establish clinical effects of the whole molecule; they do not separate every receptor’s contribution.
Mazdutide: GLP-1 + Glucagon
Mazdutide adds glucagon receptor activity. Glucagon’s effects on liver metabolism provide a rationale for studying liver fat and energy expenditure. The GLORY-1 authors describe glucagon-driven lipid oxidation as a possible explanation for metabolic changes, not proof that a measured portion of human weight loss came from thermogenesis.
Why This Matters
The receptor difference helps explain why researchers study different metabolic outcomes. It does not establish that mazdutide has better liver effects, or that GIP causes a higher weight-loss percentage in another trial. Those questions require appropriately designed comparisons.
Weight Loss Comparison
Mazdutide Trial Results
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| Trial | Dose | Duration | Weight Loss | Participants |
|---|---|---|---|---|
| GLORY-2 | 9 mg | 60 weeks | −16.65% (treatment-policy) | 462 randomized |
| GLORY-1 | 6 mg | 48 weeks | -14.01% | 610 |
| GLORY-1 | 4 mg | 48 weeks | -11.00% | 610 |
A U.S. Phase 2 study published in August 2026 adds evidence beyond the Chinese GLORY program. It randomized 179 adults without diabetes and studied doses up to 16 mg for 48 weeks. At the primary 32-week endpoint, the 16 mg group had 18.1% mean weight loss versus 0.9% with placebo under the efficacy estimand. Adverse-event discontinuation reached 20% at 16 mg, so the low GLORY discontinuation rates cannot be generalized to every mazdutide regimen.
Tirzepatide Trial Results
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| Trial | Dose | Duration | Weight Loss | Participants |
|---|---|---|---|---|
| SURMOUNT-1 | 15 mg | 72 weeks | −20.9% | 2,539 |
| SURMOUNT-1 | 10 mg | 72 weeks | −19.5% | 2,539 |
| SURMOUNT-1 | 5 mg | 72 weeks | −15.0% | 2,539 |
These are treatment-regimen estimates, versus 3.1% loss with placebo. SURMOUNT-1 also reported 22.5% loss with 15 mg versus 2.4% with placebo under the efficacy estimand, which assumes continued treatment. The trial excluded diabetes and included BMI of at least 30, or at least 27 with a weight-related complication.
Cross-Trial Comparison
GLORY-2 lasted 60 weeks and included some participants with type 2 diabetes; SURMOUNT-1 lasted 72 weeks and excluded diabetes. Baseline characteristics, treatment support and statistical methods also differ. Their results cannot establish how the drugs would compare in the same population or predict an individual response.
Innovent’s June 2026 program update describes an ongoing direct comparison of high-dose mazdutide with tirzepatide. Until results are available, the older placebo-controlled trials should not be presented as a substitute.
Side Effects and Tolerability
Both trials reported frequent gastrointestinal adverse events. Low discontinuation is not the same as a low frequency of symptoms or absence of serious risks.
| Trial and dose | Stopped treatment because of adverse events |
|---|---|
| GLORY-1: mazdutide 4 mg / 6 mg / placebo | 1.5% / 0.5% / 1.0% |
| GLORY-2: mazdutide 9 mg / placebo | 2.9% / 0% |
| SURMOUNT-1: tirzepatide 5 mg / 10 mg / 15 mg / placebo | 4.3% / 7.1% / 6.2% / 2.6% |
Tolerability: A Notable Difference
Mazdutide had low adverse-event discontinuation in these studies, but this does not establish best-in-class tolerability. For example, GLORY-1 reported nausea in 50.5% and vomiting in 43.1% of the 6 mg group. Its safety table also included gallbladder events and an obstructive pancreatitis event. Low discontinuation does not mean there were no other safety findings.
Different protocols and participants can affect discontinuation. These data do not show that mazdutide’s symptoms are milder for an individual or that more people would remain on it in routine care.
Liver Fat: Different Mechanisms, Different Results
The cited liver studies were not head-to-head:
- Mazdutide: Innovent reported a 71.9% relative reduction in MRI-measured liver fat at 60 weeks in a GLORY-2 subgroup without diabetes and with baseline liver fat of at least 10%, versus a 5.1% increase with placebo.
- Tirzepatide: SURPASS-3 MRI studied adults with type 2 diabetes. The pooled 10 mg and 15 mg groups had an 8.09 percentage-point absolute reduction in liver fat at 52 weeks, versus 3.38 points with insulin degludec.
An absolute percentage-point change is not a relative percentage reduction. These different measurements, populations and comparators cannot establish a 20–30-point liver advantage for mazdutide. MRI changes also do not establish MASH resolution or fibrosis reversal.
Where Retatrutide Fits: Mazdutide vs Tirzepatide vs Retatrutide
TRIUMPH-5 directly compares retatrutide with tirzepatide; its registry lists planned completion in late 2026, which is not a promised publication date. Innovent separately describes an ongoing mazdutide-versus-tirzepatide study. These trials may answer questions that separate placebo comparisons cannot.
Availability and Regulatory Status
Mazdutide has Chinese approvals for weight management and type 2 diabetes. Innovent’s June 2026 update described the 9 mg weight-management application as awaiting approval. A trial dose and a marketed dose are not automatically the same.
Tirzepatide is available by prescription in the U.S. as Mounjaro for type 2 diabetes and Zepbound for weight management and moderate-to-severe obstructive sleep apnea in eligible adults with obesity. Mounjaro also has a cardiovascular risk-reduction indication for adults with type 2 diabetes at high risk. The brand and indication matter for prescribing and coverage.
Mazdutide’s U.S. Phase 2 study is completed and published, but it does not establish a submission or approval date. No confirmed U.S. commercial availability date for mazdutide was identified.
Frequently Asked Questions
Is mazdutide better than tirzepatide for weight loss?
No published result cited here establishes that directly. The GLORY-2 and SURMOUNT-1 averages come from different populations and durations. Innovent has described an ongoing direct comparison, but its June 2026 update did not report results.
What is the difference between mazdutide and tirzepatide?
Both activate GLP-1 receptors. Mazdutide also activates glucagon receptors; tirzepatide also activates GIP receptors. The whole-molecule clinical effects must be evaluated in trials rather than inferred from receptor names alone.
Is mazdutide available in the US?
Mazdutide is not FDA-approved. Tirzepatide is FDA-approved under indication-specific Mounjaro and Zepbound labels. No confirmed U.S. commercial availability date for mazdutide was identified.
Which is better for fatty liver disease — mazdutide or tirzepatide?
The studies cited here cannot determine that. They measured liver fat in different populations and used different comparators and analysis methods. Imaging fat reduction also differs from biopsy-confirmed MASH improvement or fibrosis change.
How does retatrutide compare to mazdutide and tirzepatide?
Retatrutide targets all three receptors—GLP-1, GIP and glucagon—and remains investigational. Its separate weight and liver studies do not establish superiority over either drug. Direct comparison results are needed.
Does mazdutide have fewer side effects than tirzepatide?
Mazdutide had fewer adverse-event discontinuations in the cited GLORY trials than tirzepatide did in SURMOUNT-1. That cross-trial observation does not establish fewer symptoms, lower serious risk or better tolerability for an individual.
Will mazdutide ever be FDA approved?
That remains uncertain. Chinese approval and positive studies do not guarantee U.S. submission or FDA approval. No confirmed U.S. submission timeline was identified.
Sources
- Hsia, S.H., et al. (2026). U.S. Phase 2 mazdutide trial. PubMed
- Ji, L., et al. (2025). Mazdutide in Chinese Adults with Overweight or Obesity (GLORY-1). New England Journal of Medicine. NEJM
- Innovent Biologics. (2026). GLORY-2 results and development update. Press release
- Jastreboff, A.M., et al. (2022). Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). New England Journal of Medicine. DOI: 10.1056/NEJMoa2206038
- Eli Lilly. (2025). TRIUMPH-4 results. Press release
- ClinicalTrials.gov: Mazdutide trials
- ClinicalTrials.gov: TRIUMPH-5 head-to-head trial. NCT06662383
- Innovent Biologics. (2026). GLORY-2 and program update. Primary release
- Gao, L., et al. (2026). GLORY-2. JAMA
- Gastaldelli, A., et al. (2022). SURPASS-3 MRI. PubMed
- Eli Lilly. Mounjaro U.S. prescribing information.
- Eli Lilly. Zepbound U.S. prescribing information. Label
- 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 specific NMPA-approved indications in China. Tirzepatide has product-specific FDA approvals under the Mounjaro and Zepbound brands. Approval for one dose, indication or country does not apply automatically to another.
- Our standard
- Every claim traces to a primary source. We label the strength of evidence and flag estimates as estimates — never as clinical fact.
- No commercial ties
- 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
- GLORY-1 trial (NEJM)
New England Journal of Medicine
- SURMOUNT-1 trial (NEJM)
New England Journal of Medicine
- GLORY-2 trial
JAMA
NEJM
The Lancet
JAMA
FDA
ClinicalTrials.govRelated reading
What Is Mazdutide (Xinermei)? The First GLP-1/Glucagon Drug Approved in China
Mazdutide is approved in China. Chinese Phase 3 and US Phase 2 studies describe different doses, populations and outcomes.
Retatrutide vs Tirzepatide (Zepbound): Triple Agonist vs Dual Agonist
How retatrutide and tirzepatide differ in receptor activity, trial evidence, safety, and approval status. Direct TRIUMPH-5 results are pending.
Which GLP-1 Is Best for Weight Loss? All Five Drugs Compared
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