Mazdutide vs Retatrutide (2026): Dual vs Triple Agonist Data Compared
Mazdutide vs retatrutide: 14.0% at 48 weeks in GLORY-1 vs 28.3% at 80 weeks in TRIUMPH-1. See what adding GIP to GLP-1/glucagon agonism changes in the data.
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 retatrutide is a comparison of two generations of glucagon-containing incretin agonists: mazdutide (IBI362, LY3305677) is a once-weekly GLP-1 and glucagon receptor dual agonist approved in China, while retatrutide (LY3437943) is Eli Lilly's once-weekly triple agonist of the GIP, GLP-1 and glucagon receptors, now through three pivotal Phase 3 readouts. Both trace back to Lilly discovery programs, and both use glucagon receptor (GCGR) agonism to add energy expenditure and hepatic fat effects on top of GLP-1-driven appetite suppression. The difference is the third receptor.
Research reference only. All information on this page is a summary of peer-reviewed scientific literature and does not constitute medical advice. See individual library profiles for full compound data.
Quick Answer: Mazdutide activates two receptors (GLP-1R and GCGR) and reported 14.0% mean weight reduction at 48 weeks in the Phase 3 GLORY-1 trial. Retatrutide adds GIP receptor agonism and reported 28.3% at 80 weeks in Phase 3 TRIUMPH-1 (12 mg, efficacy estimand), though the trials differ in population, duration and dose range.
TL;DR:
- Mazdutide is a dual GLP-1R/GCGR agonist built on the oxyntomodulin sequence; retatrutide is a GIPR/GLP-1R/GCGR triple agonist.
- Phase 3 headline figures: mazdutide 14.0% at 48 weeks (GLORY-1, 6 mg); retatrutide 28.3% at 80 weeks (TRIUMPH-1, 12 mg).
- Mazdutide is approved by China's NMPA; retatrutide is investigational, with a US filing planned for Q1 2027.
- Both show large liver-fat reductions, attributed largely to the glucagon receptor component.
- Cross-trial comparison is limited: populations (Chinese vs multinational), baseline BMI and trial length all differ.
| Mazdutide | Retatrutide | |
|---|---|---|
| Receptor targets | GLP-1R + GCGR | GIPR + GLP-1R + GCGR |
| Most advanced stage | Approved in China (NMPA, 2025); Phase 3 elsewhere | Phase 3 (TRIUMPH program) |
| Headline Phase 3 weight result | −14.0% at 48 weeks, 6 mg (GLORY-1) | −28.3% at 80 weeks, 12 mg (TRIUMPH-1) |
| Phase 2 weight result | −11.3% at 24 weeks, 6 mg | −24.2% at 48 weeks, 12 mg |
| Dosing interval in trials | Once weekly, subcutaneous | Once weekly, subcutaneous |
| Developer | Innovent Biologics (China), with Eli Lilly | Eli Lilly |
Mazdutide: mechanism and evidence base
Mazdutide is a 30-amino-acid acylated peptide derived from oxyntomodulin, the gut hormone that naturally activates both the GLP-1 receptor and the glucagon receptor. A C18 fatty acid chain promotes albumin binding and supports once-weekly administration. In the published mechanism framing, the GLP-1R component mediates satiety, slows gastric emptying and enhances glucose-dependent insulin secretion, while the GCGR component drives hepatic fatty acid oxidation, lipolysis and thermogenesis.
The Phase 2 trial in Chinese adults with overweight or obesity (PMID 38092790) randomised 248 participants to once-weekly mazdutide 3 mg, 4.5 mg, 6 mg or placebo for 24 weeks. Mean body weight changes were −6.7%, −10.4% and −11.3% across the three doses, against +1.0% for placebo.
The pivotal Phase 3 GLORY-1 trial (NCT05607680), published in the New England Journal of Medicine in 2025 (PMID 40421736), enrolled 610 Chinese adults and reported −11.0% (4 mg) and −14.0% (6 mg) mean body weight change at 48 weeks versus +0.3% for placebo. Liver fat content fell by up to roughly 80% in participants with elevated baseline liver fat. Innovent has also reported results from GLORY-2, which studied a 9 mg dose in adults with BMI of 30 kg/m² or more, with mean weight reduction of up to about 20%. Gastrointestinal events (nausea, diarrhoea, vomiting) were the most commonly reported adverse events, mostly mild to moderate.
Retatrutide: mechanism and evidence base
Retatrutide is a single peptide engineered to activate three G-protein coupled receptors: GIPR, GLP-1R and GCGR. It adds GIP receptor agonism, the mechanism that distinguishes tirzepatide from GLP-1-only agonists, to the GLP-1/glucagon pairing used by mazdutide.
Preclinical work has examined how much each receptor contributes. A 2026 Molecular Metabolism study (PMID 41997446) reported that retatrutide normalised body weight in diet-induced obese mice lacking a functional GLP-1 receptor, and that combined GIPR and GCGR agonism alone could correct obesity in rodents. The authors framed this as evidence that the GIP and glucagon arms carry substantial weight-lowering activity independent of GLP-1R signalling.
In humans, the Phase 2 obesity trial published in the New England Journal of Medicine in 2023 (PMID 37366315) randomised 338 adults to retatrutide 1 mg to 12 mg or placebo. At 48 weeks, the 12 mg group reported −24.2% mean body weight change versus −2.1% for placebo. The Phase 3 TRIUMPH-1 trial (NCT05929066) in 2,339 adults without diabetes then reported −28.3% at 80 weeks with 12 mg under the efficacy estimand (−25.0% under the treatment-regimen estimand). In type 2 diabetes, the Phase 3 TRANSCEND-T2D-1 trial was published in The Lancet in 2026 (PMID 42250575). Full TRIUMPH program detail is in the retatrutide Phase 3 results summary.
Side-by-side comparison
| Parameter | Mazdutide | Retatrutide |
|---|---|---|
| Code names | IBI362, LY3305677 | LY3437943 |
| Structural basis | Oxyntomodulin analogue, C18 acylation | Multi-agonist peptide backbone, fatty acid acylation |
| GIPR activity | None | Yes |
| GLP-1R activity | Yes | Yes |
| GCGR activity | Yes | Yes |
| Route and interval | Subcutaneous, once weekly | Subcutaneous, once weekly |
| Phase 3 doses studied | 4 mg, 6 mg (GLORY-1); 9 mg (GLORY-2) | 4 mg, 9 mg, 12 mg (TRIUMPH-1) |
| Phase 3 population | Chinese adults, overweight or obesity | Multinational adults, obesity with comorbidity |
| Liver fat signal | Up to ~80% reduction (GLORY-1 subgroup) | Large reductions reported in Phase 2 MASLD substudy |
| Primary research applications | Obesity, type 2 diabetes, hepatic steatosis | Obesity, type 2 diabetes, MASLD, cardiovascular and renal outcomes |
The 28.3% vs 14.0% gap should not be read as a direct ranking. GLORY-1 ran for 48 weeks at doses up to 6 mg in a population with lower average baseline BMI; TRIUMPH-1 ran for 80 weeks at doses up to 12 mg in a population with a mean baseline BMI of 40. Longer trials at higher doses typically report larger reductions, and no head-to-head trial of the two compounds has been registered. The trial tracker lists the registered Phase 3 studies for both programs.
Differential research applications
The central research question these two compounds pose is what GIP receptor agonism adds when GLP-1R and GCGR are already engaged. Retatrutide's preclinical data (PMID 41997446) suggest GIPR and GCGR agonism are complementary, with GIP agonism possibly offsetting some of glucagon's hyperglycaemic tendency. Mazdutide provides the two-receptor baseline: researchers studying the incremental contribution of GIPR can compare dual GLP-1R/GCGR data against triple-agonist data at matched time points.
Researchers focused on hepatic outcomes often select GLP-1/glucagon dual agonists such as mazdutide or survodutide, because the glucagon component acts directly on hepatocyte lipid metabolism. Retatrutide also shows marked liver-fat reductions, so the choice there typically depends on whether the study design requires isolating glucagon's contribution without GIP signalling.
For population-specific work, mazdutide has the deepest dataset in East Asian cohorts, while retatrutide's TRIUMPH program covers multinational populations, including adults with established cardiovascular disease. Researchers comparing incretin-class compounds against the GLP-1-only reference point usually anchor to semaglutide. Pharmacokinetic comparisons across once-weekly incretin peptides can be viewed on the half-life chart.
Regulatory and compounding status
| Jurisdiction | Mazdutide | Retatrutide |
|---|---|---|
| FDA (US) | Not approved; investigational | Not approved; investigational, BLA submission planned Q1 2027 |
| EMA (EU) | Not approved | Not approved |
| NMPA (China) | Approved in 2025 for chronic weight management, with 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; falls under S0 (non-approved substances) outside China | Not named; falls under S0 as a non-approved substance |
Neither compound is a lawful 503A or 503B bulk drug substance in the United States. The FDA has issued warnings about unapproved retatrutide sold online, and the same reasoning applies to mazdutide outside China. The PCAC tracker follows compounding-list decisions for peptides under FDA review.
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 37366315, "Triple-Hormone-Receptor Agonist Retatrutide for Obesity, A Phase 2 Trial" (New England Journal of Medicine, 2023). https://doi.org/10.1056/NEJMoa2301972
- PMID 41997446, "GIPR:GCGR co-agonism restores normal weight in obese rodents" (Molecular Metabolism, 2026). https://doi.org/10.1016/j.molmet.2026.102365
- PMID 42250575: "Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial" (The Lancet, 2026).
Frequently asked questions
Q: What is the difference between mazdutide and retatrutide?
A: Mazdutide is a dual agonist of the GLP-1 and glucagon receptors, while retatrutide is a triple agonist that also activates the GIP receptor. Mazdutide is developed by Innovent with Eli Lilly and is approved in China; retatrutide is developed by Eli Lilly and remains investigational.
Q: Which produced more weight loss in trials, mazdutide or retatrutide?
A: Retatrutide's Phase 3 TRIUMPH-1 trial reported 28.3% at 80 weeks (12 mg), and mazdutide's Phase 3 GLORY-1 trial reported 14.0% at 48 weeks (6 mg). The trials differ in length, dose, population and baseline BMI, so the figures cannot be ranked directly, and no head-to-head trial exists.
Q: How does tirzepatide compare with retatrutide and mazdutide?
A: Tirzepatide activates GIP and GLP-1 receptors, mazdutide activates GLP-1 and glucagon receptors, and retatrutide activates all three. Each pairing tests a different hypothesis about which receptor combination drives weight and metabolic effects, which is why the three are often studied together.
Q: Is mazdutide approved in the United States?
A: No. Mazdutide was approved by China's NMPA in 2025 but has no FDA or EMA approval. It remains investigational outside China.
Q: Why do both compounds target the glucagon receptor?
A: Glucagon receptor agonism increases hepatic fatty acid oxidation and energy expenditure, effects that complement GLP-1-driven appetite reduction. Both programs report large liver-fat reductions, which researchers attribute largely to the glucagon component.
See also:
- Mazdutide vs Survodutide: the two leading GLP-1/glucagon dual agonists compared
- Mazdutide vs Tirzepatide: glucagon vs GIP as the second receptor alongside GLP-1
- Retatrutide Phase 3 Results: full TRIUMPH-1, -2 and -3 data tables
For laboratory research purposes only. Not for human or animal consumption. Compounds described are not approved by the FDA for human or veterinary use unless explicitly stated.