Mazdutide

Mazdutide is a once-weekly injectable peptide that activates two receptors at the same time: the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). It carries the development codes IBI362 and LY3305677, and in China it is marketed under the brand name Xinermei. Its regulatory significance is specific and worth stating precisely: it is the first GLP-1/glucagon dual agonist to obtain marketing approval anywhere in the world, which makes it the opening data point for an entire pharmacological class rather than simply another entrant in a crowded field.

The compound's origin is often misreported, so it is worth being exact. Mazdutide came out of Eli Lilly's research into oxyntomodulin-based co-agonists. In 2019 Lilly licensed the molecule to Innovent Biologics, a biopharmaceutical company based in Suzhou, China, which took on clinical development and commercialization in China. Lilly retained rights in the rest of the world. That split explains the shape of the evidence base: nearly all of the pivotal clinical work has been conducted in Chinese populations by Innovent, while Lilly has run a smaller, separate early-phase program in the United States.

Structurally, mazdutide is a synthetic analogue of oxyntomodulin, a naturally occurring gut hormone that is a product of the same proglucagon gene that gives rise to both GLP-1 and glucagon. Oxyntomodulin is itself a weak dual agonist at both receptors, so mazdutide is better understood as an engineered improvement on an existing human signaling molecule than as an entirely synthetic construct. The engineered peptide is 33 amino acids long, includes a non-coded alpha-aminoisobutyric acid residue at position 2 to resist enzymatic degradation, and carries a C20 fatty diacid chain attached through a hydrophilic linker at the lysine in position 20. That fatty acid binds albumin in plasma, which slows clearance and supports once-weekly administration.

Mazdutide sits within a broader generation of multi-receptor metabolic peptides. If you are new to the category, our overview of next-generation GLP-1 and incretin therapeutics explains how single agonists, dual agonists and triple agonists differ in design intent. This guide is educational and does not constitute medical advice.

The GLP-1 arm of mazdutide does what GLP-1 receptor agonists have been shown to do for more than a decade. It enhances glucose-dependent insulin secretion from pancreatic beta cells, suppresses inappropriate glucagon release when glucose is high, slows gastric emptying, and acts on hypothalamic and brainstem circuits to reduce appetite and food intake. This arm accounts for most of the glycemic effect and a substantial share of the reduction in energy intake.

The glucagon arm is the part that distinguishes mazdutide, and it is counterintuitive. Glucagon is best known as the hormone that raises blood glucose by driving hepatic glucose output, which seems like the last thing a diabetes or obesity drug should do. The rationale for adding it rests on glucagon's other actions: glucagon receptor activation increases resting energy expenditure, promotes hepatic fatty acid oxidation and lipolysis, and reduces liver fat content. In other words, where GLP-1 primarily reduces energy intake, glucagon is intended to increase energy output and to act directly on hepatic lipid handling.

The design bet is that the GLP-1 component's insulin-promoting and glucagon-suppressing effects more than offset the hyperglycemic tendency of glucagon receptor activation, leaving a net benefit on both glucose and weight plus an additional metabolic effect that GLP-1 alone does not deliver. This is why the balance of potency between the two receptors matters so much in this class, and why different dual agonists are not interchangeable. The ratio of GLP-1R to GCGR activity is a deliberate engineering choice, and it differs between mazdutide and other dual agonists such as survodutide.

Two practical consequences follow from the mechanism. First, the glucagon component creates a set of safety questions that pure GLP-1 drugs do not raise in the same way, including effects on heart rate, hepatic enzymes and glucose in people with impaired beta-cell reserve. Second, the hepatic lipid effects have made metabolic dysfunction-associated steatotic liver disease a logical area of investigation for the class, and mazdutide is under clinical evaluation in that setting as well as in obstructive sleep apnea. Those indications remain investigational and are not approved anywhere.

Mazdutide's first regulatory approval came in June 2025, when China's National Medical Products Administration (NMPA) authorized it for long-term body weight management in adults with a body mass index of 28 kg/m² or higher, or a BMI of 24 kg/m² or higher accompanied by at least one weight-related comorbidity. These thresholds are lower than the ones used in Western labeling because Chinese and other East Asian populations develop cardiometabolic complications at lower BMI values, and Chinese clinical guidelines define overweight and obesity accordingly.

A second Chinese approval followed in September 2025, covering glycemic control in adults with type 2 diabetes. Mazdutide therefore holds two separate indications in China, each supported by its own phase 3 program: the GLORY studies for weight management and the DREAMS studies for diabetes. Innovent has also sought to extend the weight management label to a higher 9 mg dose on the basis of the GLORY-2 trial, and has announced approval in Macao.

Outside China, the picture is simple: mazdutide has no approval from the US Food and Drug Administration, the European Medicines Agency, the MHRA, Health Canada or the TGA. It is an investigational agent in all of those jurisdictions. Any product sold in those markets as mazdutide is not an approved medicine, and the legal status of possessing or importing it varies by country.

It is worth noting how recent all of this is. The first approval is roughly sixteen months old at the time of writing, and the diabetes indication is younger still. Real-world safety databases for mazdutide are correspondingly thin compared with semaglutide or tirzepatide, which have been on the market for years and have accumulated postmarketing surveillance across millions of patient-years. A first-in-class approval establishes that a regulator found the benefit-risk balance acceptable in a defined population. It does not substitute for long-term pharmacovigilance.

GLORY-1 is the pivotal weight management trial and the basis of the Chinese obesity approval. It was a multicenter, double-blind, randomized, placebo-controlled phase 3 study in 610 Chinese adults aged 18 to 75 with obesity, or with overweight plus at least one weight-related comorbidity, with a mean age of 34.2 years. Participants received once-weekly subcutaneous mazdutide 4 mg, mazdutide 6 mg or placebo. The co-primary endpoints were assessed at week 32, with treatment continuing to week 48. The results were published in the New England Journal of Medicine in 2025, reportedly the first phase 3 trial of a Chinese-developed metabolic drug to appear in that journal.

At week 32, mean percentage change in body weight from baseline was a reduction of 10.09% on 4 mg and 12.55% on 6 mg, against a 0.45% gain on placebo. By week 48, the reductions had deepened to 11.00% and 14.01% respectively, with placebo at a 0.30% gain. Secondary analyses reported that roughly 36% of the 4 mg group and about 50% of the 6 mg group achieved a weight reduction of 15% or more by week 48, compared with about 2% on placebo. Weight loss had not clearly plateaued by the end of the treatment period, which is a common pattern in this drug class.

GLORY-2 tested a higher dose. It was a double-blind, placebo-controlled phase 3 trial at 27 Chinese hospitals, running from December 2023 to November 2025, in adults with a BMI of 30 kg/m² or higher with or without type 2 diabetes. Participants were randomized 2:1 to once-weekly mazdutide 9 mg (n = 308) or placebo (n = 154) for 60 weeks, alongside a reduced-calorie diet and increased physical activity. At week 60, mean body weight change was a reduction of 16.65% with mazdutide versus 1.50% with placebo, and 84.3% of the mazdutide group lost at least 5% of body weight compared with 33.1% on placebo. The trial also reported improvements in systolic blood pressure, triglycerides, non-HDL cholesterol and LDL cholesterol. Results were published in JAMA in 2026.

Earlier dose-ranging work set up these trials. A phase 2 study published in Nature Communications in 2023 randomized 248 Chinese participants to mazdutide 3 mg, 4.5 mg, 6 mg or placebo, and reported week-24 mean weight changes of a 6.7%, 10.4% and 11.3% reduction respectively versus a 1.0% gain on placebo. Before that, a phase 1b multiple-ascending-dose trial published in eClinicalMedicine in 2022 evaluated 9 mg and 10 mg cohorts over 12 and 16 weeks at five Chinese hospitals, following an earlier phase 1b study that had shown up to 6.4% weight loss over 12 weeks at doses up to 6 mg.

The one dataset in a non-Chinese population is a US-based phase 2 trial published in The Lancet Diabetes & Endocrinology in 2026. It randomized 179 adults with obesity, or overweight with at least one weight-related condition, across 24 US centers to placebo, an escalating lower-dose regimen from 3 mg to 6 mg, 10 mg, or 16 mg. At 32 weeks, adjusted mean weight reductions were 7.3%, 15.6% and 18.1% for the lower-dose, 10 mg and 16 mg groups, versus 0.9% on placebo. The doses cited throughout this section are trial protocol doses reported for context. They are not recommendations, and none of this information should be used to self-administer anything.

While GLORY addressed weight management, the DREAMS program tested mazdutide in type 2 diabetes and supported the September 2025 Chinese approval for glycemic control. The two programs are frequently confused, so the distinction is worth holding onto: GLORY for obesity, DREAMS for diabetes.

DREAMS-1 was a randomized, double-blind, placebo-controlled phase 3 trial in Chinese adults with type 2 diabetes inadequately controlled by diet and exercise alone. Innovent announced in 2024 that it had met its primary endpoint and all key secondary endpoints, with superior glycemic control and weight reduction versus placebo, a low incidence of hypoglycemia, no severe hypoglycemia, and no new safety signals. The results were presented at the American Diabetes Association's 85th Scientific Sessions.

DREAMS-2 is the more informative study because it used an active comparator rather than placebo. It was a multicenter randomized phase 3 trial in 731 Chinese adults with type 2 diabetes inadequately controlled on metformin, assigned to mazdutide 4 mg, mazdutide 6 mg or dulaglutide 1.5 mg for 28 weeks. Both mazdutide doses were non-inferior and then superior to dulaglutide on HbA1c change at week 28, with least-squares mean treatment differences of 0.24 percentage points for 4 mg and 0.30 percentage points for 6 mg. The weight separation was larger: least-squares mean treatment differences in body weight of 3.78% for 4 mg and 5.76% for 6 mg in favor of mazdutide. Significantly more mazdutide participants reached the composite endpoint of HbA1c below 7.0% together with at least 5% weight loss. Results were published in Nature in 2026.

A third study, DREAMS-3, compared mazdutide 6 mg directly against semaglutide 1 mg over 32 weeks in 349 Chinese adults with early-stage type 2 diabetes and obesity. Innovent reported in late 2025 that mean weight reduction was 10.29% with mazdutide versus 6.00% with semaglutide, and that 48.0% versus 21.0% of participants reached a composite endpoint of HbA1c below 7.0% with at least 10% weight loss. Two caveats are important here. These figures come from a sponsor press release rather than a peer-reviewed publication, and semaglutide 1 mg is a diabetes dose rather than the 2.4 mg dose used for weight management, so the comparison does not speak to semaglutide's maximal weight effect.

Taken together, the DREAMS results support a consistent pattern: mazdutide produces glycemic improvements broadly comparable to or modestly better than established GLP-1 agonists in these populations, with a clearer advantage on body weight. Whether that advantage translates into better long-term cardiovascular, renal or hepatic outcomes is an entirely separate question that these trials were not designed to answer.

Across the mazdutide trial program, the adverse event profile is dominated by gastrointestinal effects. Diarrhea, nausea and vomiting are the most frequently reported treatment-emergent events, they are predominantly mild to moderate in severity, and they cluster during the dose-escalation period before easing with continued treatment. This pattern is familiar from the GLP-1 class generally, and our article on GLP-1 side effects covers the mechanisms and clinical management of these symptoms in more detail.

Discontinuation rates in GLORY-1 were low. Adverse events led to stopping the trial regimen in 1.5% of the 4 mg group, 0.5% of the 6 mg group and 1.0% of the placebo group. In the US phase 2 trial, discontinuation for adverse events was more frequent at the higher 10 mg and 16 mg doses than at lower doses or placebo, which is the expected dose-response relationship for tolerability in this class. Mean heart rate changes reported in GLORY-1 remained small, on the order of a few beats per minute, and the published trial did not report a cardiovascular safety signal over its 48-week duration.

The glucagon component raises mechanism-specific questions that should be monitored distinctly from GLP-1 effects. Glucagon receptor activation can in principle affect heart rate, hepatic aminotransferase levels, amino acid metabolism and glucose control in individuals with limited beta-cell reserve. The trials conducted so far have not flagged these as prohibitive problems in the populations studied, but they are the issues that long-term surveillance of this class will need to resolve, and absence of a signal in a 48-week or 60-week trial is not the same as established long-term safety.

Several important safety domains remain genuinely open. There are no completed cardiovascular outcome trials for mazdutide. Pregnancy, lactation and pediatric use have not been adequately studied. Class-level warnings established for GLP-1 receptor agonists, including pancreatitis, gallbladder disease, and thyroid C-cell tumors observed in rodents, should be assumed to require consideration until mazdutide-specific long-term data exist. Interactions with other glucose-lowering drugs, particularly insulin and sulfonylureas, affect hypoglycemia risk.

This section summarizes published trial findings for educational purposes. It is not a safety assessment for any individual, it deliberately contains no dosing or titration guidance, and it cannot substitute for the approved prescribing information and the judgment of a qualified prescriber who knows your medical history.

Survodutide (BI 456906), developed by Boehringer Ingelheim with Zealand Pharma, is the closest mechanistic comparator to mazdutide because it is also a GLP-1 and glucagon receptor dual agonist. In the 76-week phase 3 SYNCHRONIZE-1 trial, conducted across 116 sites in 14 countries in adults with obesity, mean body weight fell 12.2% with survodutide 3.6 mg and 13.0% with 6.0 mg, versus 5.4% with placebo, and 28.5% of participants on the 6.0 mg dose achieved at least a 20% reduction compared with 6.6% on placebo. Survodutide has not received marketing approval, so mazdutide retains the first-in-class position.

Tirzepatide is a different mechanism entirely. It is a GIP and GLP-1 receptor dual agonist, so its second receptor is the glucose-dependent insulinotropic polypeptide receptor rather than the glucagon receptor. In the 72-week SURMOUNT-1 trial, mean weight change at week 72 was a reduction of 15.0% on 5 mg, 19.5% on 10 mg and 20.9% on 15 mg, against 3.1% on placebo. Retatrutide extends the logic further as a triple GIP, GLP-1 and glucagon receptor agonist, and is discussed in our retatrutide guide.

Reading that table as a ranking would be a mistake, and this is the single most important caveat in the article. These are separate trials in different populations with different designs. The mazdutide pivotal trials enrolled Chinese adults with a mean baseline BMI and mean age well below those in SURMOUNT-1 or SYNCHRONIZE-1, and GLORY-1 participants had a mean age of 34.2 years. Treatment durations differ by 16 to 28 weeks across these studies, which matters because weight loss curves in this class had not plateaued at the endpoints reported. Placebo-group behavior also differs markedly, from a slight weight gain in GLORY-1 to a 5.4% loss in SYNCHRONIZE-1, which alone shifts any placebo-subtracted comparison.

No head-to-head trial of mazdutide against tirzepatide has been published. Until one exists, any claim that one of these agents produces more weight loss than another is an inference across non-comparable datasets rather than a finding. The only direct comparisons available for mazdutide are against dulaglutide (published in Nature) and against semaglutide 1 mg (sponsor-reported only).

As a prescription medicine, no. Mazdutide is approved and commercially available in China, where Innovent holds the rights, and has been announced as approved in Macao. Eli Lilly holds the rights outside China and has published a US phase 2 trial in The Lancet Diabetes & Endocrinology in 2026, but as of October 2026 no phase 3 program or regulatory filing for mazdutide outside China has been publicly announced. There is accordingly no approved route to obtain mazdutide by prescription in the United States, the European Union, the United Kingdom, Canada or Australia.

Material sold online as mazdutide in those markets therefore falls outside the regulated pharmaceutical supply chain. Such products are typically labeled for laboratory research use only, are not manufactured to pharmaceutical standards, and are not subject to the identity, purity, sterility, endotoxin and potency testing that applies to an approved injectable medicine. Independent analyses of grey-market peptide vendors have repeatedly found discrepancies between labeled and actual content, including underdosing, incorrect compounds and contamination. Klow Peptide does not sell or recommend any source for mazdutide and includes no purchase links in this guide.

The legal position varies by jurisdiction and is worth understanding rather than assuming. In most countries, selling an unapproved drug for human use is unlawful, importation may be seized by customs, and administering an unapproved injectable to yourself carries no liability protection, no pharmacovigilance pathway and no clinical oversight. Mazdutide is also a peptide hormone analogue, which places it within categories monitored by anti-doping authorities. Competitive athletes should assume it is prohibited and verify with their governing body.

For readers in the US or EU whose underlying interest is an approved therapy for obesity or type 2 diabetes, several options have full marketing authorization, established labeling and postmarketing safety data. Discussing those with a physician is a materially different proposition from sourcing an unapproved peptide. That conversation is the appropriate next step, and nothing in this guide should be read as encouragement to do otherwise.

The most consequential gap is long-term outcomes. The longest published randomized exposure for mazdutide specifically is 60 weeks, in GLORY-2. No cardiovascular outcome trial for mazdutide has reported, so whether its weight and glycemic effects translate into fewer heart attacks, strokes, hospitalizations for heart failure or deaths is unknown. For context, that evidence took years to accumulate for semaglutide and tirzepatide after their initial approvals.

The second gap is generalizability. Every pivotal mazdutide trial was conducted in China, in a population with lower mean BMI and lower mean age than typical Western obesity trials, and against BMI thresholds specific to Chinese guidelines. The US phase 2 trial in 179 participants is the main non-Chinese dataset, and a phase 2 trial is not designed to establish efficacy or safety at a regulatory standard. How mazdutide performs in older, heavier and more comorbid Western populations has not been established in phase 3.

The third gap concerns durability and discontinuation. Weight regain after stopping is well documented across the GLP-1 class, and there is no reason to assume mazdutide behaves differently, but trials designed specifically to characterize what happens after withdrawal have not been published. Related questions include whether the glucagon-driven increase in energy expenditure is sustained over years rather than months, and how body composition changes are distributed between fat mass and lean mass over extended treatment.

Finally, several investigational indications remain unresolved. Mazdutide is under clinical evaluation in metabolic dysfunction-associated steatotic liver disease, obstructive sleep apnea and alcohol use disorder, and early hepatic fat findings have been encouraging, but none of these uses is approved anywhere and none should be presented as an established benefit. Readers tracking how the broader multi-agonist field is developing may find our overview of next-generation incretin therapeutics a useful companion.

Medical disclaimer: this article is for educational purposes only and reports published clinical findings. It is not medical advice, contains no dosing or protocol recommendations, and must not be used to guide self-treatment. Mazdutide is not approved by the FDA or the EMA. Legal status differs by jurisdiction. Always consult a qualified healthcare professional before considering any pharmacological intervention for weight or metabolic health.