Mazdutide (research codes IBI362 and LY3305677) is a laboratory-made peptide that activates two “switches” on cells at once: the GLP-1 receptor (the same one semaglutide acts on) and the glucagon receptor. It was modelled on oxyntomodulin — a gut hormone that naturally acts on both of these receptors. It was developed by Eli Lilly and is being developed in China by Innovent Biologics; in June 2025 it was approved there as a medicine for weight management, and in September 2025 for the treatment of type 2 diabetes. Outside China it is not approved. The evidence for weight loss is strong (phase 3 trials published in the NEJM, JAMA and “Nature”), but it comes almost entirely from China, and the popular claim of “more than 20% at 48 weeks” has no support in the published results. Below we set out what is known.
What mazdutide is
Mazdutide is an analogue of oxyntomodulin — a hormone released by cells of the gut after a meal. Natural oxyntomodulin activates the GLP-1 receptor and the glucagon receptor, but circulates in the blood for only a few minutes. Mazdutide has a fatty-acid chain attached that extends its action to a full week — which is why it is given once weekly (Ji et al., 2023). The compound's history is unusual: the molecule was discovered by the American company Eli Lilly (hence the code LY3305677), and the rights to develop it in China were bought by Innovent Biologics (code IBI362). As a result, almost the entire clinical programme — from the first trials in 2020–2021 through to approval — was carried out in China, where the medicine is sold under the name Xinermei (Shirley, 2025). The first trial outside China, a phase 2 study in the USA, did not appear until August 2026.
How it works — two receptors at once
The “GLP-1” part works like the familiar incretin medicines: it suppresses appetite, slows stomach emptying and improves insulin secretion. The “glucagon” part is the idea for something more: in the liver, glucagon increases fat burning and — according to research on the class as a whole — raises energy expenditure, which is meant to give greater weight loss than GLP-1 alone. This has a price, though: glucagon stimulates the heart, so dual agonists raise heart rate more than GLP-1 medicines do. In the Chinese phase 2 trial (Ji et al., 2023) heart rate after 24 weeks had risen by 5.4–8.8 beats per minute depending on the dose, against 4.8 on placebo, and in the phase 1b study at the 6 mg dose by as much as 15 beats; the authors note that in the second half of treatment heart rate no longer rose and returned to normal after stopping. It should be added that increased energy expenditure was not directly measured in humans in the mazdutide trials — it is an inference from the class mechanism, not a measured effect.
What was studied in animals — fat in the liver
The most interesting animal data concern the liver. In a study with 9.4 T magnetic resonance imaging (Xia et al., 2025) mice fed a high-fat diet for 13 weeks received mazdutide, semaglutide or saline for 4 weeks. The liver fat fraction fell more after mazdutide than after semaglutide (median −5.59 versus −3.30 percentage points; p = 0.02), and the MRI measurement agreed well with histology. This shows that the glucagon component really does “add” something to GLP-1 alone in the liver — at least in mice. In humans, the available data so far are a 23–29% fall in the liver enzyme ALT in phase 2 (against 3% on placebo) and improved liver enzymes in the meta-analysis (Kamrul-Hasan et al., 2026); a phase 3 trial comparing mazdutide with semaglutide in people with fatty liver disease (NCT06884293) is ongoing.
Human data — obesity
In phase 2 (Ji et al., 2023) 248 Chinese adults with overweight or obesity received mazdutide 3, 4.5 or 6 mg once weekly or placebo for 24 weeks; body weight fell by 6.7%, 10.4% and 11.3% respectively, while on placebo it rose by 1.0%. The phase 3 GLORY-1 trial (Ji et al., 2025) enrolled 610 people and lasted 48 weeks: at 32 weeks (the primary endpoint) body weight had fallen by 10.09% on 4 mg and 12.55% on 6 mg against a rise of 0.45% on placebo, and at 48 weeks by 11.00% and 14.01% against +0.30%; at least 15% of body weight was lost by 35.7% of people on 4 mg and 49.5% on 6 mg (2.0% on placebo). The higher 9 mg dose was tested in GLORY-2 (Gao et al., 2026): 461 people with obesity (BMI of at least 30, mean age 34), 60 weeks; body weight fell by 16.65% against 1.50% on placebo, and at least 5% was lost by 84.3% of those treated against 33.1%. The first data from outside China (Hsia et al., 2026; 179 people in the USA, sponsored by Eli Lilly) showed at 32 weeks −7.3% on the 3–6 mg dose, −15.6% on 10 mg and −18.1% on 16 mg against −0.9% on placebo — but on 16 mg, 20% of participants stopped treatment because of adverse events. A meta-analysis of nine trials (Kamrul-Hasan et al., 2026; 2,292 people) confirms the dose-dependent effect: −6.6% (3 mg), −9.9% (4 mg) and −11.1% (6 mg) relative to placebo, with the caveat of very low certainty of evidence owing to the small number of trials and their heterogeneity.
Human data — type 2 diabetes
In the phase 3 DREAMS-1 trial (Zhu et al., 2026) 320 people with type 2 diabetes not yet on medication received mazdutide 4 or 6 mg or placebo; after 24 weeks glycated haemoglobin (HbA1c) had fallen by 1.57 and 2.15 percentage points against 0.14 on placebo, and body weight by 5.61% and 7.81% against 1.26%. In DREAMS-2 (Guo et al., 2026) 731 patients were compared with dulaglutide 1.5 mg — an approved GLP-1 medicine: after 28 weeks mazdutide lowered HbA1c by a further 0.24 (4 mg) and 0.30 points (6 mg) and body weight by a further 3.78% and 5.76%; gastrointestinal complaints were more frequent with it. On this basis the Chinese regulator also approved mazdutide for diabetes (Shirley, 2025). A trial comparing it with semaglutide in people with diabetes and obesity (DREAMS-3, NCT06184568) was completed in 2025; its results have not yet been published.
Safety and the limits of the evidence
The side-effect profile is above all gastrointestinal, and more markedly so than with GLP-1 alone: in GLORY-2 on 9 mg, vomiting was reported by 53.1% of people (1.3% on placebo), nausea by 46.9% (3.2%) and diarrhoea by 39.4% (6.5%); most events were mild to moderate, and 2.9% of people stopped treatment because of adverse events against 0% on placebo. In GLORY-1 the discontinuation rate was 0.5–1.5%. Added to this is the rise in heart rate described above. The evidence has three limitations. First, almost all the data come from a Chinese population with a lower BMI than in Western trials (a mean of 31 in GLORY-1) — the meta-analysis explicitly calls for multi-ethnic and longer studies. Second, there are no published data on the effect on heart attacks and strokes, or on safety beyond 60 weeks. Third, outside China mazdutide is not approved — the Drugs@FDA database lists no product containing it (as of September 2026), and Eli Lilly's US programme is at the phase 2 stage. All the registration trials were funded by Innovent, and some of the authors are its employees. The data concern a pharmaceutical-grade medicine with gradual dose escalation under supervision — they do not carry over to products from the unregulated market. We deliberately give no methods of use and no doses.
The wider context — dual GLP-1 and glucagon agonists
Mazdutide belongs to the same group as survodutide (see our piece on survodutide) and differs from tirzepatide, which adds the GIP receptor to GLP-1 instead of glucagon (tirzepatide), and from retatrutide, which activates all three (retatrutide). Within this group mazdutide is the most advanced: it has marketing approval, although for now in a single country. An overview of the whole group can be found in our text on GLP-1, GIP and glucagon peptides.
Summary
Mazdutide is a once-weekly oxyntomodulin analogue acting on the GLP-1 and glucagon receptors. In Chinese phase 3 trials it lowered body weight by 14% (6 mg, 48 weeks) and by 16.7% (9 mg, 60 weeks), and in type 2 diabetes it was more effective than dulaglutide; in the American phase 2 trial the 16 mg dose gave 18.1% at 32 weeks at the cost of 20% of participants stopping treatment. The published results do not support the slogan “more than 20% at 48 weeks on 9 mg” — no such figure appears in any peer-reviewed trial. It is approved only in China; it raises heart rate and frequently causes nausea, vomiting and diarrhoea. The evidence for efficacy is strong but geographically narrow and short, and the human liver data are so far limited to liver enzymes.
Sources
- Kamrul-Hasan ABM, Chatterjee S, Ashraf H, et al. Efficacy and Safety of the Dual Glucagon-Like Peptide-1 and Glucagon Receptor Agonist Mazdutide in Predominantly Chinese Adults With Obesity and/or Type 2 Diabetes: A Systematic Review and Meta-Analysis. Diabetes, Obesity & Metabolism. 2026;28(10):8777–8794. PMID: 42410325. DOI: 10.1111/dom.71058. pubmed.ncbi.nlm.nih.gov/42410325
- Ji L, Jiang H, Bi Y, et al.; GLORY-1 Investigators. Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight. The New England Journal of Medicine. 2025;392(22):2215–2225. PMID: 40421736. DOI: 10.1056/NEJMoa2411528. pubmed.ncbi.nlm.nih.gov/40421736
- Gao L, Jiang H, Cai H, et al.; GLORY-2 Trial Investigators. Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial. JAMA. 2026;336(5):377–388. PMID: 42251595. DOI: 10.1001/jama.2026.8142. pubmed.ncbi.nlm.nih.gov/42251595
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- Guo L, Zhang B, Xue X, et al.; DREAMS-2 investigators. Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes. Nature. 2026;652(8108):181–188. PMID: 41407860. DOI: 10.1038/s41586-025-10031-z. pubmed.ncbi.nlm.nih.gov/41407860
- Hsia SH, Bays HE, Billings LK, et al. Efficacy and safety of mazdutide in adults with obesity or overweight: a US-based, multicentre, phase 2, randomised, placebo-controlled clinical trial. The Lancet Diabetes & Endocrinology. 2026;online ahead of print (Aug 21). PMID: 42628555. DOI: 10.1016/S2213-8587(26)00160-9. pubmed.ncbi.nlm.nih.gov/42628555
- Ji L, Jiang H, Cheng Z, et al. A phase 2 randomised controlled trial of mazdutide in Chinese overweight adults or adults with obesity. Nature Communications. 2023;14(1):8289. PMID: 38092790. DOI: 10.1038/s41467-023-44067-4. pubmed.ncbi.nlm.nih.gov/38092790
- Shirley M. Mazdutide: First Approval. Drugs. 2025;85(12):1621–1627. PMID: 41028652. DOI: 10.1007/s40265-025-02249-y. pubmed.ncbi.nlm.nih.gov/41028652
- Xia H, Min Y, Wang Y, et al. Multiparametric MRI Evaluation of Liver Fat and Iron after Glucagon-like Peptide-1 Receptor and Glucagon Receptor Dual-Agonist Treatment in a High-Fat Diet-induced Mouse Model. Radiology. 2025;316(2):e243780. PMID: 40828048. DOI: 10.1148/radiol.243780. pubmed.ncbi.nlm.nih.gov/40828048
For in-vitro laboratory research only. It is not a human medicine and is not for treatment.