Mazdutide vs Survodutide (2026): GLP-1/Glucagon Dual Agonist Phase 3 Data Compared
Mazdutide vs survodutide: Phase 3 data show 14.0% weight loss at 48 weeks vs 16.6% at 76 weeks. Compare liver-fat results, approval status and key differences.
Research reference only. The information in this article is a summary of peer-reviewed scientific literature. It does not constitute medical advice and is not intended to guide human use. See our full disclaimer.
Mazdutide vs survodutide is the closest like-for-like comparison in the GLP-1/glucagon dual agonist class: both are once-weekly acylated peptides that activate the GLP-1 receptor (GLP-1R) and the glucagon receptor (GCGR), and both have now reported Phase 3 obesity data. The differences sit in developer, trial population, dose range and regulatory path. Mazdutide (IBI362, LY3305677) has been approved in China, while survodutide (BI 456906) is still investigational and is being developed with an emphasis on liver disease.
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Quick Answer: Mazdutide and survodutide both target GLP-1R and GCGR. Mazdutide's Phase 3 GLORY-1 trial reported a 14.0% mean weight reduction at 48 weeks (6 mg) in Chinese adults, and survodutide's Phase 3 SYNCHRONIZE-1 trial reported 16.6% at 76 weeks (6.0 mg, efficacy estimand) in a multinational population. Mazdutide is approved in China. Survodutide remains investigational and is furthest along in MASH research.
TL;DR:
- Same receptor pair (GLP-1R + GCGR), once-weekly injection for both, from different developers (Innovent/Lilly vs Boehringer Ingelheim/Zealand)
- Mazdutide: Phase 3 GLORY-1, -14.0% at 48 weeks (6 mg); NMPA approval in China in 2025
- Survodutide: Phase 3 SYNCHRONIZE-1, -16.6% at 76 weeks (6.0 mg); FDA Breakthrough Therapy designation for MASH
- Liver fat reduction is the class differentiator, and both programs report large relative reductions
- The trials differ in length, population and estimand, so cross-trial figures are not directly comparable
| Parameter | Mazdutide | Survodutide |
|---|---|---|
| Target | GLP-1R / GCGR dual agonist | GCGR / GLP-1R dual agonist |
| Most advanced stage | Approved in China (NMPA, 2025); Phase 3 elsewhere | Phase 3 (obesity, MASH) |
| Headline weight figure | -14.0% at 48 weeks, 6 mg (GLORY-1) | -16.6% at 76 weeks, 6.0 mg (SYNCHRONIZE-1) |
| Placebo comparator | +0.3% at 48 weeks | -3.2% at 76 weeks |
| Dosing interval | Once weekly, subcutaneous | Once weekly, subcutaneous |
| Developer | Innovent Biologics (China), Eli Lilly (ex-China) | Boehringer Ingelheim (licensed from Zealand Pharma) |
Mazdutide: mechanism and evidence base
Mazdutide is a 30-amino-acid peptide derived from the oxyntomodulin sequence, with a C18 fatty acid chain for albumin binding and once-weekly exposure. Oxyntomodulin is the gut hormone that naturally activates both GLP-1R and GCGR. Mazdutide is engineered to keep that dual activity while extending half-life. In the published mechanism framing, the GLP-1R component drives satiety, slower gastric emptying and glucose-dependent insulin secretion. The GCGR component is associated with increased energy expenditure, hepatic fatty acid oxidation and lipolysis.
The first randomised evidence came from a Phase 2 trial in 248 Chinese adults with overweight or obesity. That trial reported mean body weight changes of -6.7%, -10.4% and -11.3% at 24 weeks for the 3 mg, 4.5 mg and 6 mg arms, against +1.0% with placebo (PMID 38092790). A later Phase 2 study tested a 9 mg dose in adults with a BMI of at least 30 kg/m².
Phase 3 GLORY-1 (NCT05607680), published in the New England Journal of Medicine in 2025, randomised 610 Chinese adults to mazdutide 4 mg, 6 mg or placebo for 48 weeks. Mean weight changes were reported at -11.0% and -14.0% against +0.3% for placebo, with liver fat reductions of up to roughly 80% in participants with elevated baseline liver fat (PMID 40421736). The DREAMS-1 and DREAMS-2 trials extended the program into type 2 diabetes.
Survodutide: mechanism and evidence base
Survodutide is a 29-amino-acid acylated peptide, also carrying a C18 fatty acid moiety. Boehringer Ingelheim licensed it from Zealand Pharma. Compared with mazdutide, survodutide is generally described as having relatively greater glucagon receptor engagement, which researchers link to its emphasis on hepatic outcomes.
In a 46-week Phase 2 dose-finding trial in adults with a BMI of at least 27 kg/m², the 4.8 mg arm produced the largest weight reduction, and the dose-response pattern informed Phase 3 dose selection (DOI 10.1016/S2213-8587(23)00356-X). A separate 48-week Phase 2 trial in biopsy-confirmed MASH with F1–F3 fibrosis reported MASH improvement without worsening of fibrosis in up to 83% of survodutide-treated participants, against 18% with placebo (PMID 38847460). Those results led to FDA Breakthrough Therapy designation and EMA PRIME designation for MASH.
The Phase 3 SYNCHRONIZE-1 trial enrolled adults with obesity or overweight without type 2 diabetes for 76 weeks. Baseline characteristics were published in 2026 (PMID 41187967). Topline results released in April 2026 reported mean weight reductions of 15.3% (3.6 mg) and 16.6% (6.0 mg) under the efficacy estimand, against 3.2% with placebo. Under the treatment-regimen estimand the figures were 12.2% and 13.0%, against 5.4% with placebo. The 6.0 mg arm also reported a 63.1% relative reduction in liver fat content, against 24.5% with placebo.
Side-by-side comparison
| Feature | Mazdutide | Survodutide |
|---|---|---|
| Code names | IBI362, LY3305677 | BI 456906 |
| Structural basis | Oxyntomodulin analogue, 30 aa, C18 acylation | Glucagon-based analogue, 29 aa, C18 acylation |
| Receptor emphasis | Balanced GLP-1R/GCGR | Relatively greater GCGR engagement |
| Route and interval | Subcutaneous, once weekly | Subcutaneous, once weekly |
| Phase 3 doses studied | 4 mg, 6 mg (GLORY-1); 9 mg in GLORY-2 | 3.6 mg, 6.0 mg (SYNCHRONIZE-1) |
| Phase 3 population | Chinese adults | Multinational adults |
| Phase 3 duration | 48 weeks | 76 weeks |
| Liver-fat signal | Up to ~80% reduction (GLORY-1 subgroup) | 63.1% relative reduction (SYNCHRONIZE-1, 6.0 mg) |
| MASH-specific program | Exploratory | Phase 3 (Breakthrough Therapy, PRIME) |
| Most common adverse events | Nausea, diarrhoea, vomiting | Nausea, vomiting, diarrhoea |
Half-life and pharmacokinetic comparisons for once-weekly incretin-class peptides can be viewed on the half-life chart.
Differential research applications
Although the receptor pair is the same, the published literature suggests the two compounds are used to answer slightly different questions.
Hepatic outcomes. Survodutide is the more common choice for studies centred on MASH, fibrosis and liver fat. Its Phase 2 MASH trial used biopsy endpoints (PMID 38847460), and its development program includes dedicated Phase 3 liver studies. Researchers studying the glucagon arm's contribution to hepatic lipid handling often cite survodutide as the reference GCGR-weighted dual agonist.
Population-specific efficacy. Mazdutide has the largest body of randomised data in East Asian adults, including Phase 2 and Phase 3 trials enrolling at lower BMI thresholds (BMI ≥24 or ≥28 kg/m², per Chinese obesity criteria). That makes it the relevant compound for research into how dual agonism performs at lower BMI cut-offs (PMID 38092790).
Dose-ceiling questions. The 9 mg mazdutide program and its higher weight-reduction figures in adults with a BMI of at least 30 kg/m² are often discussed in work on whether GCGR co-agonism can approach the efficacy reported for triple agonists such as retatrutide.
Class context. Both compounds sit alongside pemvidutide, another GLP-1/glucagon dual agonist with a liver-focused program, and the GIP/GLP-1 agonist tirzepatide, which is the usual reference comparator. Active and recruiting trials for all of these compounds can be followed in the clinical trial tracker.
Cross-trial comparisons need caution. GLORY-1 and SYNCHRONIZE-1 differ in duration (48 vs 76 weeks), population, placebo response (+0.3% vs -3.2%) and the estimand used for the headline figure. No head-to-head trial of mazdutide against survodutide has been registered.
Regulatory and compounding status
| Jurisdiction | Mazdutide | Survodutide |
|---|---|---|
| FDA (US) | Not approved; investigational | Not approved; Breakthrough Therapy and Fast Track for MASH |
| EMA (EU) | Not approved | Not approved; PRIME designation for MASH |
| NMPA (China) | Approved in 2025 for chronic weight management, with later type 2 diabetes indication | Not approved |
| 503A compounding (US) | Not an FDA-approved drug component; not on the 503A bulks list | Not an FDA-approved drug component; not on the 503A bulks list |
| WADA | Not named; check the current Prohibited List (S0 covers substances without government approval) | Not named; falls under S0 as a non-approved substance |
Compounding-eligibility changes and Pharmacy Compounding Advisory Committee reviews are tracked on the PCAC tracker.
Cited studies
- PMID 38092790, "A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity" (Nature Communications, 2023). https://doi.org/10.1038/s41467-023-44067-4
- PMID 40421736: "Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight" (New England Journal of Medicine, 2025). https://doi.org/10.1056/NEJMoa2411528
- PMID 41187967, "Survodutide for treatment of obesity: Baseline characteristics of participants in a randomized, double-blind, placebo-controlled, phase 3 trial (SYNCHRONIZE-1)" (Diabetes, Obesity and Metabolism, 2026). https://doi.org/10.1111/dom.70196
- PMID 38847460, "A Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis" (New England Journal of Medicine, 2024). https://doi.org/10.1056/NEJMoa2401755
- Survodutide Phase 2 obesity dose-finding trial (Lancet Diabetes & Endocrinology, 2024). https://doi.org/10.1016/S2213-8587(23)00356-X
- Boehringer Ingelheim, SYNCHRONIZE-1 topline results (April 2026). https://www.boehringer-ingelheim.com/us/human-health/metabolic-diseases/results-phase-iii-synchronize-1-obesity-trial
Frequently asked questions
Q: What is the difference between mazdutide and survodutide?
A: Both are once-weekly GLP-1 and glucagon receptor dual agonists. Mazdutide is an oxyntomodulin-based peptide from Innovent and Eli Lilly that is approved in China, while survodutide is a Boehringer Ingelheim and Zealand Pharma peptide that remains investigational. Survodutide's program places more emphasis on MASH and liver outcomes.
Q: Which showed more weight loss in Phase 3, mazdutide or survodutide?
A: GLORY-1 reported a 14.0% mean reduction at 48 weeks with mazdutide 6 mg, and SYNCHRONIZE-1 reported 16.6% at 76 weeks with survodutide 6.0 mg under the efficacy estimand. The trials differed in length, population and analysis method, so the numbers cannot be ranked directly.
Q: Is mazdutide approved anywhere?
A: Yes. China's NMPA approved mazdutide in 2025, making it the first GLP-1/glucagon dual agonist approved in any market. It is not approved by the FDA or EMA.
Q: Why is survodutide studied for MASH?
A: Glucagon receptor activation is associated with hepatic fatty acid oxidation and reduced liver fat. A Phase 2 biopsy trial reported MASH improvement without fibrosis worsening in up to 83% of survodutide-treated participants, which led to FDA Breakthrough Therapy designation.
Q: How do mazdutide and survodutide compare with retatrutide?
A: Retatrutide adds GIP receptor agonism to the GLP-1 and glucagon pair, making it a triple agonist. Its published weight-reduction figures have generally been higher than those of dual agonists, although no trial has compared these compounds head to head.
See also:
- Pemvidutide vs Survodutide: the other liver-focused GLP-1/glucagon dual agonist comparison
- Mazdutide vs Tirzepatide: mazdutide against the GIP/GLP-1 reference compound
- Survodutide and the SYNCHRONIZE trials: a full overview of the survodutide Phase 3 program
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