Mazdutide vs Tirzepatide: GLP-1/Glucagon vs GLP-1/GIP Compared
Mazdutide and tirzepatide are both dual-receptor agonists for weight loss and type 2 diabetes — but they activate completely different second receptors. Tirzepatide (Zepbound/Mounjaro) pairs GLP-1 with GIP to enhance insulin signaling and appetite suppression. Mazdutide (Xinermei) pairs GLP-1 with glucagon to increase energy expenditure and drive liver fat oxidation.
Tirzepatide is FDA-approved and widely available. Mazdutide is approved only in China and is not available in the US or Europe. In clinical trials, tirzepatide has produced greater overall weight loss, while mazdutide shows dramatically better liver fat reduction and remarkably low discontinuation rates.
This page compares the two drugs using published clinical trial data, explains how their mechanisms differ, and shows where Eli Lilly's triple agonist retatrutide fits into the picture.
Side-by-Side Comparison
| Mazdutide (Xinermei) | Tirzepatide (Zepbound / Mounjaro) | |
|---|---|---|
| Developer | Innovent Biologics (molecule from Eli Lilly) | Eli Lilly |
| Mechanism | Dual agonist: GLP-1 + Glucagon | Dual agonist: GLP-1 + GIP |
| Receptors | GLP-1 + Glucagon | GLP-1 + GIP |
| Max weight loss (trials) | -20.1% at 60 weeks (GLORY-2, 9 mg, non-T2D subgroup) | -22.5% at 72 weeks (SURMOUNT-1, 15 mg) |
| Max dose tested | 9 mg weekly | 15 mg weekly |
| FDA status | Not approved — approved in China only | FDA approved (Zepbound 2023, Mounjaro 2022) |
| Administration | Once-weekly injection | Once-weekly injection |
| Liver fat reduction | 72-80% | ~50-55% |
| Discontinuation rate (AEs) | 0.5-2.9% | 4-7% |
| Unique advantage | Glucagon-driven liver fat clearance and thermogenesis | Established safety profile, broad availability |
How the Mechanisms Differ
Both drugs share GLP-1 receptor agonism — the same target used by semaglutide (Ozempic/Wegovy). The GLP-1 component suppresses appetite, slows gastric emptying, and improves insulin secretion. Where they diverge is the second receptor.
Tirzepatide: GLP-1 + GIP
Tirzepatide adds GIP (glucose-dependent insulinotropic polypeptide) on top of GLP-1. GIP enhances insulin sensitivity, amplifies the satiety signal from GLP-1, and may directly influence fat cell metabolism. The result is a potent dual incretin combination that primarily works by reducing calorie intake through powerful appetite suppression.
This approach has been remarkably successful. Tirzepatide produced the highest weight loss of any FDA-approved obesity medication to date (22.5% at the maximum dose in SURMOUNT-1).
Mazdutide: GLP-1 + Glucagon
Mazdutide takes a fundamentally different approach by pairing GLP-1 with glucagon receptor activation. Glucagon is a catabolic hormone that acts primarily on the liver. When activated, it:
- Promotes hepatic fat oxidation — the liver breaks down stored fat at an accelerated rate
- Increases energy expenditure through thermogenesis
- Stimulates lipolysis — the breakdown of stored fat in adipose tissue
This means mazdutide attacks obesity from both sides of the energy equation: reduced intake (GLP-1) and increased expenditure (glucagon). Tirzepatide works almost entirely on the intake side.
Why This Matters
The glucagon component is why mazdutide shows dramatically better liver fat reduction than tirzepatide (72-80% vs ~50-55%). For patients with metabolic dysfunction-associated steatotic liver disease (MASLD), the glucagon mechanism directly targets the organ where fat accumulation causes the most metabolic damage.
However, tirzepatide's GIP component appears to produce greater overall weight loss. The two drugs represent different strategic trade-offs, not simply different dosages of the same approach.
Weight Loss Comparison
Mazdutide Trial Results
| Trial | Dose | Duration | Weight Loss | Participants |
|---|---|---|---|---|
| GLORY-2 | 9 mg | 60 weeks | -18.55% (all); -20.1% (non-T2D) | 462 |
| GLORY-1 | 6 mg | 48 weeks | -14.01% | 610 |
| GLORY-1 | 4 mg | 48 weeks | -11.00% | 610 |
The GLORY-2 trial (reported November 2025) tested the higher 9 mg dose of mazdutide in Chinese adults with obesity (BMI 30 or above). Among participants without type 2 diabetes, 48.7% achieved 20% or greater weight loss at 60 weeks. Notably, weight loss was still continuing at week 60 with no plateau observed.
Tirzepatide Trial Results
| Trial | Dose | Duration | Weight Loss | Participants |
|---|---|---|---|---|
| SURMOUNT-1 | 15 mg | 72 weeks | -22.5% | 2,539 |
| SURMOUNT-1 | 10 mg | 72 weeks | -21.4% | 2,539 |
| SURMOUNT-1 | 5 mg | 72 weeks | -16.0% | 2,539 |
SURMOUNT-1 was a larger trial (2,539 participants) conducted over a longer duration (72 weeks) in a predominantly Western population. At the maximum 15 mg dose, 63% of participants achieved 20% or greater weight loss.
Cross-Trial Comparison
| Metric | Mazdutide 9 mg (GLORY-2) | Tirzepatide 15 mg (SURMOUNT-1) |
|---|---|---|
| Mean weight loss | -18.55% at 60 weeks | -22.5% at 72 weeks |
| Achieved 20% or more weight loss | 44.0% (all); 48.7% (non-T2D) | 63% (15 mg) |
| Trial population | Chinese adults, BMI 30 or above | Global population, BMI 30 or above |
| Weight loss still declining at end? | Yes — no plateau at week 60 | Approaching plateau by week 72 |
Important caveats: These results come from different trials with different populations. Chinese participants may have different metabolic responses than Western populations. The trial durations differ (60 vs 72 weeks), and mazdutide showed no plateau at its endpoint, suggesting additional weight loss may have occurred with longer treatment. A head-to-head trial would be needed for a definitive comparison.
Side Effects and Tolerability
Both drugs produce gastrointestinal side effects typical of the GLP-1 drug class. The key difference is in discontinuation rates.
| Mazdutide (GLORY trials) | Tirzepatide (SURMOUNT-1) | |
|---|---|---|
| Most common side effects | Nausea, diarrhea, decreased appetite, vomiting | Nausea, diarrhea, vomiting, constipation |
| Severity | Mostly mild-moderate, transient | Mostly mild-moderate, during dose escalation |
| Discontinuation rate (AEs) | 0.5-1.5% (GLORY-1); 2.9% (GLORY-2, 9 mg) | 4.3-7.1% across dose groups |
| Unique signals | None beyond GI class effects | Gallbladder/biliary risk |
Tolerability: A Notable Difference
Mazdutide's discontinuation rates are the lowest reported for any GLP-1-class drug in Phase 3 obesity trials. In GLORY-1 (6 mg dose), only 0.5-1.5% of participants stopped treatment due to side effects. Even the higher 9 mg dose in GLORY-2 showed just 2.9% discontinuation — still lower than tirzepatide's range of 4-7%.
This suggests that more patients can complete the full treatment course on mazdutide, which may partially offset the lower per-patient weight loss compared to tirzepatide.
Liver Fat: Different Mechanisms, Different Results
| Drug | Liver Fat Reduction | Source |
|---|---|---|
| Mazdutide 9 mg | -71.9% | GLORY-2 MASLD substudy |
| Mazdutide (Phase 2) | -73-80% | Phase 2 MASLD substudy |
| Tirzepatide | ~50-55% | SURMOUNT trials |
Mazdutide's glucagon receptor activation directly promotes hepatic fat oxidation — the liver breaks down stored fat at an accelerated rate. This produces liver fat reductions that are 20-30 percentage points greater than tirzepatide. For patients with MASLD (formerly NAFLD), this difference could be clinically significant.
Where Retatrutide Fits: Mazdutide vs Tirzepatide vs Retatrutide
Eli Lilly's retatrutide bridges both approaches. As a triple agonist (GLP-1 + GIP + glucagon), retatrutide has everything tirzepatide has plus the glucagon component that distinguishes mazdutide. It targets all three receptors in a single molecule.
| Drug | Receptors | Max Weight Loss | Liver Fat Reduction | Status |
|---|---|---|---|---|
| Mazdutide 9 mg | GLP-1 + Glucagon | -20.1% (60 wks, non-T2D) | 72-80% | Approved in China only |
| Tirzepatide 15 mg | GLP-1 + GIP | -22.5% (72 wks) | ~50-55% | FDA approved |
| Retatrutide 12 mg | GLP-1 + GIP + Glucagon | -28.7% (68 wks) | 82-86% | Phase 3 (not approved) |
The pattern is clear: adding glucagon receptor agonism (mazdutide, retatrutide) improves liver fat reduction beyond what GLP-1/GIP alone achieves. Adding GIP (tirzepatide, retatrutide) appears to drive greater absolute weight loss. Retatrutide, with all three receptors, shows the highest numbers in both categories.
However, these are cross-trial comparisons. Different populations, durations, and endpoints make direct ranking imprecise. Eli Lilly's TRIUMPH-5 trial (comparing retatrutide vs tirzepatide head-to-head, results expected ~2027) will settle part of this question, but no trial is planned to compare all three drugs directly.
For detailed breakdowns, see Retatrutide vs Tirzepatide and Retatrutide vs Mazdutide.
Availability and Regulatory Status
| Mazdutide | Tirzepatide | |
|---|---|---|
| Approved for obesity | China only (Xinermei, June 2025) | FDA approved (Zepbound, November 2023) |
| Approved for T2D | China only (Xinermei, September 2025) | FDA approved (Mounjaro, May 2022) |
| Available in the US | No — US Phase 2 trials ongoing | Yes |
| Brand name | Xinermei (China) | Zepbound (obesity) / Mounjaro (T2D) |
| Developer | Innovent Biologics | Eli Lilly |
| 9 mg dose status | NDA submitted to China NMPA (November 2025) | N/A |
| Monthly cost | Available at Chinese retail pricing | ~$1,060/month (Zepbound, US list price) |
Mazdutide is currently only available in China. There is no established timeline for FDA submission, and US availability would likely be several years away even under an optimistic scenario. The mazdutide molecule was originally discovered by Eli Lilly and licensed to Innovent Biologics for development in the Chinese market — Lilly separately developed retatrutide as its own next-generation drug for global markets.
Tirzepatide is FDA-approved and available by prescription in the US under two brand names: Zepbound (for chronic weight management) and Mounjaro (for type 2 diabetes).
Frequently Asked Questions
Is mazdutide better than tirzepatide for weight loss?
Based on current trial data, tirzepatide produces greater overall weight loss. Tirzepatide 15 mg achieved 22.5% weight loss at 72 weeks (SURMOUNT-1), while mazdutide 9 mg achieved 18.55% at 60 weeks (GLORY-2). However, these come from different trials and populations. Mazdutide showed no weight loss plateau at 60 weeks, suggesting the gap could narrow with longer treatment.
What is the difference between mazdutide and tirzepatide?
Both are dual-receptor agonists that share GLP-1 activity, but they target different second receptors. Tirzepatide activates GLP-1 and GIP (enhanced insulin signaling and appetite suppression). Mazdutide activates GLP-1 and glucagon (increased energy expenditure and liver fat oxidation). They use fundamentally different biological strategies for weight loss.
Is mazdutide available in the US?
No. Mazdutide is approved only in China under the brand name Xinermei. US Phase 2 trials are ongoing, but there is no established timeline for FDA submission. Tirzepatide (Zepbound/Mounjaro) is the only dual-agonist obesity drug currently available in the US.
Which is better for fatty liver disease — mazdutide or tirzepatide?
Mazdutide shows substantially greater liver fat reduction (72-80%) compared to tirzepatide (~50-55%). This is because mazdutide activates the glucagon receptor, which directly promotes hepatic fat oxidation. For patients with MASLD (fatty liver disease), mazdutide's mechanism may offer specific advantages, though head-to-head liver fat trials have not been conducted.
How does retatrutide compare to mazdutide and tirzepatide?
Retatrutide is a triple agonist that combines the receptors from both drugs — GLP-1 (shared by both), GIP (from tirzepatide), and glucagon (from mazdutide). In trials, retatrutide showed the highest weight loss (28.7%) and the best liver fat reduction (82-86%) of the three. It is not approved anywhere and is still in Phase 3 trials. See our full retatrutide vs tirzepatide comparison.
Does mazdutide have fewer side effects than tirzepatide?
Both drugs cause similar gastrointestinal side effects (nausea, diarrhea, vomiting). However, mazdutide has notably lower discontinuation rates — 0.5-2.9% across trials compared to 4-7% for tirzepatide. This suggests mazdutide's side effects are generally milder or more tolerable, allowing more patients to complete treatment.
Will mazdutide ever be FDA approved?
It is uncertain. US Phase 2 trials are ongoing, but no FDA submission timeline has been established. The molecule was originally discovered by Eli Lilly and licensed to Innovent Biologics for the Chinese market. Lilly has focused its global development efforts on retatrutide instead. If mazdutide does pursue FDA approval, it would likely be several years away.
Sources
- Ji, L., et al. (2025). Mazdutide in Chinese Adults with Overweight or Obesity (GLORY-1). New England Journal of Medicine. NEJM
- Innovent Biologics. (2025). Mazdutide 9 mg Achieves Up to 20.1% Weight Loss in Chinese Adults with Obesity — GLORY-2 Study Results. 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. (2025). Mazdutide (Xinermei) prescribing information and regulatory filings. Innovent
This article is for informational purposes only and does not constitute medical advice. Mazdutide (Xinermei) is approved in China but is not approved by the U.S. Food and Drug Administration (FDA). Tirzepatide is FDA-approved as Zepbound (obesity) and Mounjaro (type 2 diabetes). Always consult a healthcare provider before starting any medication. This site is not affiliated with Innovent Biologics, Eli Lilly, or any pharmaceutical manufacturer.
Sources
- GLORY-1 trial (NEJM)
New England Journal of Medicine
- SURMOUNT-1 trial (NEJM)
New England Journal of Medicine
- GLORY-2 results
Innovent Biologics
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