Retatrutide vs Mazdutide: Comparing Triple-Agonist and Dual GLP-1/Glucagon Trial Data
TL;DR: Mazdutide, the first GLP-1/glucagon dual agonist approved anywhere (China, 2025), reports smaller trial losses than retatrutide.
What Is Mazdutide and How Does It Differ From Retatrutide?
Mazdutide (also known as IBI362) is a once-weekly, subcutaneously injected peptide that activates two hormone receptors from a single molecular backbone: the glucagon receptor (GCGR) and the GLP-1 receptor (GLP-1R).[1] It was originally developed by Eli Lilly, which licensed the China rights to Innovent Biologics in 2018; under that arrangement Innovent develops and commercialises mazdutide within China, while Lilly retains rights to develop it everywhere else.[2]
The two-receptor design puts mazdutide in the same broad category as survodutide, another GCG/GLP-1 dual agonist — but it is structurally and mechanistically distinct from retatrutide, Eli Lilly's own single-molecule triple agonist, which is engineered to activate GLP-1, GIP and glucagon receptors together. Adding glucagon-receptor activity to GLP-1 agonism is a hypothesis several development programmes are testing in parallel: the added glucagon signalling is thought to increase energy expenditure and hepatic fat oxidation on top of GLP-1's appetite and gastric-emptying effects, a mechanistic angle retatrutide's TRIUMPH data and mazdutide's own trials are each generating independent evidence on.[3]
Neither compound is licensed for any use in the UK. Mazdutide is a marketed prescription pharmaceutical in China and remains an unapproved investigational drug everywhere else; retatrutide remains in late-stage clinical development globally, with no marketing application yet submitted anywhere.
What Did the GLORY-1 Obesity Trial Report?
Design: 610 Chinese adults with obesity or overweight and at least one weight-related comorbidity (mean baseline weight 87.2kg, mean BMI 31.1 kg/m²) were randomised to once-weekly mazdutide 4mg, 6mg, or placebo over 48 weeks. Co-primary endpoints were percentage change in body weight from baseline and the proportion achieving ≥5% weight loss at week 32.[1]
Result at week 32: mean body-weight change of −10.09% (4mg) and −12.55% (6mg) versus +0.45% on placebo; 73.9% (4mg) and 82.0% (6mg) of participants reached ≥5% weight loss versus 10.5% on placebo. Result at week 48: mean body-weight change of −11.00% (4mg) and −14.01% (6mg), with placebo showing minimal change (p<0.001 for both doses versus placebo).
Source: PMID 40421736; N Engl J Med, DOI 10.1056/NEJMoa2411528
GLORY-1 is the pivotal trial underlying mazdutide's Chinese obesity approval. Its 48-week duration and Chinese-adult-only enrolment are both narrower than retatrutide's 80–104-week TRIUMPH-1 programme, which recruited a larger and more geographically diverse population — a difference worth keeping in mind before treating the two datasets as directly comparable.[4]
What Did DREAMS-1 and DREAMS-2 Report in Type 2 Diabetes?
Design: 320 Chinese adults with type 2 diabetes inadequately controlled by diet and exercise alone were randomised to mazdutide 4mg, 6mg, or placebo over 24 weeks. Result: adjusted mean HbA1c change of −1.58 percentage points (4mg) and −2.02 percentage points (6mg) versus −0.25 on placebo; 66.4% (4mg) and 81.8% (6mg) of participants reached HbA1c <7% versus 11.7% on placebo.[5]
Design: 731 Chinese adults with type 2 diabetes and insufficient glycaemic control on metformin were randomised 1:1:1 to mazdutide 4mg, mazdutide 6mg, or dulaglutide 1.5mg over 28 weeks — a head-to-head trial against an approved GLP-1 comparator rather than placebo. Result: adjusted mean HbA1c change of −1.61 percentage points (4mg) and −1.66 percentage points (6mg) versus −1.36 for dulaglutide, meeting statistical superiority over the active comparator at the 6mg dose.[6]
Source: Innovent Biologics company announcement, 17 December 2025, reporting Phase 3 results published in Nature
DREAMS-1 and DREAMS-2 formed part of the evidence base for mazdutide's second NMPA approval, for glycaemic control in type 2 diabetes, granted 19 September 2025 — separate from, and three months after, its obesity approval.[7]
How Do Mazdutide and Retatrutide's Trial Data Compare Side by Side?
| Compound & dose | Trial (phase) | n | Duration | Reported result |
|---|---|---|---|---|
| Mazdutide 6mg | GLORY-1 obesity (Phase 3) | 610 | 48 wks | −14.01% weight vs placebo |
| Mazdutide 6mg | DREAMS-1, T2D monotherapy (Phase 3) | 320 | 24 wks | −2.02pp HbA1c vs −0.25pp placebo |
| Mazdutide 6mg | DREAMS-2 vs dulaglutide (Phase 3) | 731 | 28 wks | −1.66pp HbA1c (superior to −1.36pp) |
| Retatrutide 12mg | TRIUMPH-1 obesity (Phase 3) | 2,339 | 80 wks | −28.3% weight (up to −30.3% at 104 wks) |
| Retatrutide | TRIUMPH-2, T2D + obesity (Phase 3) | 1,152 | 80 wks | up to −20.8% weight; A1C −1.6pp |
Figures are as reported in each publication, at different durations, populations, dosing regimens and receptor mechanisms. This table is for contextual research reference only and is not a head-to-head clinical comparison; mazdutide's trials enrolled Chinese adults exclusively, while TRIUMPH enrolled a broader international population.
Retatrutide's published TRIUMPH figures are substantially larger than mazdutide's GLORY-1 and DREAMS results in absolute terms, but the comparison is complicated by trial length (48 weeks versus 80), population (China-only versus international), and receptor pharmacology (dual versus triple agonism). What the data most clearly shows is that mazdutide is the more clinically mature product by regulatory status — it is already a prescribed medicine in one major market — while retatrutide's larger reported effect sizes come from a compound still working through Phase 3 completion and a not-yet-filed marketing application.
Why Does Mazdutide's China-First Approval Path Matter for Incretin Research?
First regulatory approval for the dual GCG/GLP-1 mechanism
Mazdutide's 27 June 2025 NMPA clearance is the first time any regulator anywhere has approved a dual glucagon/GLP-1 receptor agonist for chronic weight management, ahead of survodutide, pemvidutide, and retatrutide's own triple-agonist mechanism reaching any market.[2] That gives researchers real-world prescribing and post-marketing data on the glucagon-receptor-addition hypothesis years before an equivalent Western approval is likely.
Two approvals, three months apart, from the same trial programme
NMPA cleared mazdutide for obesity in June 2025 and for type 2 diabetes glycaemic control in September 2025, treating the same molecule as two separate regulatory products with separate pivotal trials (GLORY for weight, DREAMS for glycaemia) — a structure that mirrors how retatrutide's own TRIUMPH programme separates obesity, diabetes, sleep apnoea and osteoarthritis into distinct registrational trials.
A head-to-head win over an approved GLP-1 drug, not just placebo
DREAMS-2 is one of the few Phase 3 incretin trials to report statistical superiority over an active, approved comparator (dulaglutide) rather than placebo alone — a higher evidentiary bar that most competing programmes, including retatrutide's TRIUMPH trials to date, have not yet attempted against a marketed drug.
What's Next for Mazdutide Outside China?
As of September 2026, mazdutide has not been submitted for approval to the FDA, the EMA, or the MHRA. Eli Lilly holds development rights outside China and has run earlier-phase studies internationally, but no Phase 3 programme or filing timeline for a non-Chinese market has been publicly confirmed. Innovent has separately reported DREAMS-3, a head-to-head Phase 3 trial versus semaglutide, and continues to expand mazdutide's China label toward additional indications.[8]
That timeline sits well behind retatrutide's own path. Eli Lilly confirmed on 23 July 2026 that retatrutide's Biologics License Application target has moved to Q1 2027, citing additional manufacturing and quality-control (CMC) data — see our separate coverage of the retatrutide filing delay. Whichever compound reaches Western regulators first, both remain unlicensed for any use in the UK today.
What Should UK Researchers Take From This?
Mazdutide is a licensed prescription pharmaceutical in China and a patent-protected investigational drug everywhere else, developed jointly by Innovent Biologics and Eli Lilly. It is not available for purchase, compounding, or research use from any lawful source in the UK, and Velox Peptides does not supply it. Its published trial data is presented here purely as third-party scientific context for researchers tracking the wider dual- and multi-agonist incretin field that retatrutide research sits within.
That does not change retatrutide's own regulatory position. It remains an unlicensed investigational medicine, with a Q1 2027 BLA filing target in the US and no confirmed MHRA timeline. Velox Peptides supplies retatrutide strictly as an HPLC-verified in vitro research reagent, with batch-specific certificates of analysis, and makes no therapeutic or weight-loss claims for it.
Retatrutide is supplied as a research reagent only. It is not a medicine and has not been evaluated by the MHRA or FDA for use in our products. Not for human or veterinary use. Mazdutide, IBI362 and dulaglutide are not Velox Peptides products and are not available for sale. See our Research Use Policy and MHRA Statement.
References
- Jiang H, Pang S, Zhang Y, et al. Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight (GLORY-1). N Engl J Med. Published online 9 July 2025. PMID: 40421736. DOI: 10.1056/NEJMoa2411528. pubmed.ncbi.nlm.nih.gov
- Innovent Biologics. Innovent Announces Mazdutide, First Dual GCG/GLP-1 Receptor Agonist, Received Approval from China's NMPA for Chronic Weight Management. Press release, 27 June 2025. prnewswire.com
- Müller TD, Finan B, Clemmensen C, et al. The New Biology and Pharmacology of Glucagon. Physiol Rev. 2017;97(2):721-766. PMID: 28275047. pubmed.ncbi.nlm.nih.gov
- Eli Lilly and Company. Lilly's triple agonist, retatrutide, delivered powerful weight loss in pivotal Phase 3 obesity trial (TRIUMPH-1). Press release, 21 May 2026. investor.lilly.com
- Innovent Biologics. Two Phase 3 Clinical Results of Mazdutide (GLP-1/GCG Dual Receptor Agonist) in Chinese Adults with Type 2 Diabetes Have Been Back-to-Back Published in Nature (DREAMS-1). Press release, 17 December 2025. prnewswire.com
- Innovent Biologics. Two Phase 3 Clinical Results of Mazdutide in Chinese Adults with Type 2 Diabetes Published in Nature (DREAMS-2, vs dulaglutide). Press release, 17 December 2025. prnewswire.com
- Innovent Biologics. Innovent Announces Mazdutide Received Approval from China's NMPA for Glycemic Control in Adults with Type 2 Diabetes. Press release, 19 September 2025. prnewswire.com
- Innovent Biologics. Innovent's Mazdutide Shows Superiority in Glycemic Control with Weight Loss over Semaglutide in a Head-to-head Phase 3 Clinical Trial (DREAMS-3). Press release, 2026. prnewswire.com
Frequently Asked Questions
What is mazdutide?
Mazdutide (IBI362) is a once-weekly, subcutaneously injected single-molecule peptide that activates the glucagon receptor (GCGR) and GLP-1 receptor (GLP-1R) together. It was developed by Innovent Biologics under a licensing agreement with Eli Lilly, which retains rights to mazdutide outside China while Innovent handles development and commercialisation inside China. It is not a Velox Peptides product and is not available for purchase or research use from any lawful source.
Is mazdutide approved anywhere?
Yes. China's National Medical Products Administration (NMPA) approved mazdutide for chronic weight management in adults with overweight or obesity on 27 June 2025, making it the first dual GCG/GLP-1 receptor agonist approved anywhere in the world for any indication. The NMPA approved a second indication, glycemic control in adults with type 2 diabetes, on 19 September 2025. Mazdutide has not been submitted for approval in the UK, EU, or US as of September 2026.
What did the GLORY-1 trial show?
GLORY-1 (NEJM, published online 9 July 2025; n=610 Chinese adults with obesity or overweight) reported mean body-weight reductions of 11.00% (4mg) and 14.01% (6mg) at week 48, versus a placebo arm that showed minimal change (p<0.001 for both doses). At week 32, 73.9% (4mg) and 82.0% (6mg) of participants had achieved at least 5% weight loss, versus 10.5% on placebo.
How does mazdutide compare with retatrutide's trial data?
Retatrutide's Phase 3 TRIUMPH-1 trial reported larger weight-loss figures than mazdutide's GLORY-1 trial: 28.3% at 80 weeks (up to 30.3% at 104 weeks) versus GLORY-1's 14.01% at 48 weeks on the 6mg dose. The trials differ in population, duration, dosing regimen and receptor mechanism (dual GCG/GLP-1 versus triple GLP-1/GIP/glucagon), so this is contextual comparison rather than a head-to-head study, and mazdutide is dosed and marketed only in China so far.
Is mazdutide available as a research reagent?
No. Mazdutide is a licensed pharmaceutical product in China (marketed by Innovent Biologics) and an unapproved investigational drug everywhere else, protected by patents held by Eli Lilly and Innovent. It is not available for purchase, compounding, or research use from any lawful source, and Velox Peptides does not supply it.
Is retatrutide available as a research reagent?
Yes. Velox Peptides supplies retatrutide as an HPLC-verified (≥99% purity) lyophilised research reagent for in vitro laboratory research only. It is not licensed as a medicine, is not evaluated by the MHRA or FDA, and is not intended for human or veterinary use.