Mazdutide: The GLP-1/Glucagon Drug Approved in China | Philadelphia

TL;DR30-second take

Mazdutide is a once-weekly injection that activates two hormone receptors, GLP-1 and glucagon, and it is based on a natural gut hormone called oxyntomodulin. It was developed by Innovent Biologics under license from Eli Lilly, mainly for China, where it was approved in 2025, first for weight management and then for type 2 diabetes. It is not FDA-approved and is not available in the United States. In its main weight-loss trial, GLORY-1, Chinese adults lost about 11% of their body weight on the 4 mg dose and about 14% on the 6 mg dose over 48 weeks. It also lowered blood pressure, cholesterol, liver enzymes, and uric acid, though most of those gains travel with the weight loss. Its weight numbers are more modest than the triple agonist retatrutide, and it is the first GLP-1/glucagon drug approved anywhere.

TL;DR: Mazdutide is a once-weekly injection that activates the GLP-1 and glucagon receptors, and it is modeled on oxyntomodulin, a natural gut hormone that hits both. Developed by Innovent Biologics under license from Eli Lilly, chiefly for China, it was approved there in 2025, first for weight management in June and then for type 2 diabetes in September, making it the first GLP-1/glucagon dual agonist approved anywhere. It is not FDA-approved and is not available in the United States. In its main obesity trial, GLORY-1, Chinese adults lost about 11% of their body weight on the 4 mg dose and about 14% on the 6 mg dose over 48 weeks, and the drug also improved blood pressure, lipids, liver enzymes, and uric acid, though those gains mostly track the weight loss. Its weight-loss numbers are more modest than the triple agonist retatrutide, and it sits alongside the investigational survodutide as a GLP-1/glucagon drug, with the distinction of already being approved.

What is mazdutide?

Mazdutide is a once-weekly injection that mimics two of the body's metabolic hormones at once. The first is GLP-1, the appetite-and-glucose hormone behind Ozempic and the rest of the class. The second is glucagon, which raises how much energy the body burns and acts on the liver. What makes mazdutide distinct is where its design comes from: it is based on oxyntomodulin, a natural gut hormone released after eating that itself activates both the GLP-1 and glucagon receptors. So rather than stitching together two separate drug ideas, mazdutide refines a single hormone the body already uses to do both jobs.

It is worth being precise about the receptors, because this is where drugs in this space get confused. Mazdutide targets GLP-1 and glucagon. Tirzepatide, in Mounjaro and Zepbound, targets GLP-1 and a different hormone, GIP. Retatrutide targets all three. Mazdutide does not use GIP at all.

The drug was developed by Innovent Biologics, a Chinese company, under a license from Eli Lilly, which holds the rights outside China. It was built chiefly for the Chinese market, which is where it is approved and used.

Is mazdutide approved, and can I get it in the United States?

This is the most important thing to understand about mazdutide, and the answer has two parts.

In China, mazdutide is approved. The country's drug regulator, the NMPA, cleared it for chronic weight management in June 2025, and then for glycemic control in type 2 diabetes in September 2025. So in China it is now approved for both weight and diabetes, and it holds the distinction of being the first GLP-1/glucagon dual agonist approved anywhere in the world.

In the United States, it is not. Mazdutide is not FDA-approved, and it is not available to prescribe here. Eli Lilly holds the rights outside China and has early development underway, but there is no US approval and no timeline you should count on. If you read about mazdutide's results, it is worth holding that they come from trials in Chinese adults and that the drug is, for now, a China story. The drugs available and proven here remain the approved GLP-1 and dual-agonist medications.

How much weight does mazdutide cause?

The main evidence comes from GLORY-1, a phase 3 trial in 610 Chinese adults with obesity or overweight, published in the New England Journal of Medicine.¹ People took mazdutide at 4 mg or 6 mg weekly, or a placebo, for 48 weeks.

The results held up well. People on the 4 mg dose lost about 11% of their body weight, and those on the 6 mg dose lost about 14%, compared with almost no change on placebo. Those are meaningful figures, in the range of the approved single and dual-hormone drugs, if below the very top of the field.

A separate, higher-dose trial, GLORY-2, tested a 9 mg dose and reported up to about 20% weight loss. That higher dose is under review by the Chinese regulator and is not yet approved, so it should be kept separate from the 4 mg and 6 mg doses that are. For now, the approved doses deliver the 11% to 14% seen in GLORY-1.

Set against the wider field, mazdutide's weight loss is more modest than what the triple agonist retatrutide reports, about 28% at its top dose over 80 weeks in its phase 3 program, and broadly comparable to the approved dual and single-hormone drugs. Those comparisons come from separate trials in different populations, so they are rough guides rather than head-to-head contests.

What else does mazdutide do besides weight loss?

This is where the glucagon half earns its keep, at least on paper. In GLORY-1, mazdutide improved a broad set of metabolic markers alongside the weight loss, and several of these were pre-planned secondary goals of the trial. Blood pressure came down. Triglycerides and LDL cholesterol fell. Liver enzymes dropped, and in the subgroup with fatty liver measured by imaging, liver fat fell substantially. Blood sugar and waist size improved. One that stands out is uric acid, the compound behind gout: mazdutide lowered it noticeably, more than weight loss alone would tend to, which has drawn interest in whether the glucagon action has a direct effect there.

Two cautions keep this in proportion. First, these were secondary measures in a weight-loss trial, and most of the benefit travels with the weight loss itself; the trial was not built to prove that the glucagon component adds effects independent of the pounds lost, even if that is plausible for the liver and energy-burning effects. Second, the striking liver-fat number came from the subgroup with high liver fat on imaging, so it is not a figure that applies to everyone. And a drop in uric acid in a trial is not the same as an approved treatment for gout; mazdutide is not a urate-lowering drug, and no one should think of it that way.

How is mazdutide different from survodutide and retatrutide?

All three engage the glucagon receptor, but they differ in ways that matter.

Survodutide is the closest cousin: it is also a GLP-1/glucagon dual agonist. The differences are that survodutide is investigational, not approved anywhere, and, while it has a large obesity program of its own, much of its attention has gone to MASH, the scarring form of fatty liver disease. Mazdutide, by contrast, is approved in China, is built on oxyntomodulin, and has been developed as a broad metabolic drug for weight and diabetes. So the two are mechanistic siblings on different paths: one approved and centered on weight and diabetes, the other investigational with a prominent liver program alongside obesity.

Retatrutide adds a third receptor, GIP, on top of GLP-1 and glucagon, and reports the largest weight loss of the group, though it too is investigational. Mazdutide's two-receptor design produces more modest weight loss than retatrutide's three, which is the general pattern in this class: more receptors engaged tends to mean more weight lost, along with more to learn about side effects.

The plain way to hold it: mazdutide is the only one of the three approved anywhere, and the only one based on oxyntomodulin, while survodutide and retatrutide remain in trials.

Guidance from the Clinic

"Mazdutide comes up with patients who follow the science closely, and the first thing I clarify is that it is a China drug, not something we can prescribe here. It is approved there, for both weight and diabetes, and that is a milestone, since it is the first of the glucagon-plus-GLP-1 drugs to reach approval anywhere. What I find interesting is the metabolic breadth, the way it moves blood pressure, lipids, liver fat, and uric acid, though I am careful to say that most of that rides along with the weight loss rather than standing apart from it. The weight numbers, about 11 to 14% at the approved doses, are respectable without being the highest in the field. For a patient here and now, none of this changes the plan, because the drug is not available in the United States. I keep an eye on it as a sign of where the field is heading and because Lilly may one day bring it or its lessons westward."

Key Takeaways

Mazdutide is a once-weekly GLP-1/glucagon dual agonist based on oxyntomodulin, developed by Innovent Biologics under license from Eli Lilly, chiefly for China.
It is approved in China, for weight management since June 2025 and type 2 diabetes since September 2025, the first GLP-1/glucagon drug approved anywhere. It is not FDA-approved and is not available in the United States.
In the GLORY-1 trial, Chinese adults lost about 11% of their body weight on 4 mg and about 14% on 6 mg over 48 weeks; a higher 9 mg dose reached about 20% in a separate trial but is not yet approved.
It also improved blood pressure, lipids, liver enzymes and fat, and uric acid, but these were secondary measures that mostly track the weight loss, and it is not a gout or urate treatment.
Its weight loss is more modest than the triple agonist retatrutide's; it is a mechanistic sibling of the investigational survodutide, with the distinction of already being approved.

The New Weight-Loss Drugs, Compared - where mazdutide sits in the whole field
Survodutide (GLP-1/Glucagon) - the investigational GLP-1/glucagon sibling, built for the liver
Retatrutide: The Triple Agonist - the three-receptor drug with the highest weight loss
Uric Acid and Metabolic Health - why the uric-acid effect is interesting
Tirzepatide (Zepbound, Mounjaro) - the strongest approved drug, available here
Ozempic vs Metformin - where the foundation drugs fit

Scientific References

Ji L, Jiang H, Bi Y, et al. "Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight." New England Journal of Medicine. 2025;392(22):2215-2225.
"Mazdutide, a Dual GLP-1R/GCGR Agonist, Reduces Hyperuricemia by Modulating Energy and Lipid Metabolism and Inhibiting Hepatic Purine Metabolism." Diabetes (American Diabetes Association Scientific Sessions Abstracts, preclinical study). 2025;74(Supplement 1):775-P.

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Frequently Asked Questions

Common Questions

No. Mazdutide is approved in China, where the regulator cleared it for weight management in June 2025 and for type 2 diabetes in September 2025. It is not FDA-approved and is not available to prescribe in the United States. Eli Lilly holds the rights outside China and has early development going, but there is no US approval. The drugs used in practice here are the approved GLP-1 and dual-agonist medications.

In its main trial, GLORY-1, Chinese adults lost about 11% of their body weight on the 4 mg dose and about 14% on the 6 mg dose over 48 weeks, versus almost no change on placebo. A higher 9 mg dose, tested in a separate trial, reported up to about 20%, but that dose is still under review in China and is not yet approved. The approved doses deliver roughly 11% to 14%, which is meaningful, if below the very top of the field.

Mazdutide activates the glucagon receptor in addition to GLP-1. Semaglutide (Ozempic, Wegovy) uses GLP-1 alone; tirzepatide (Mounjaro, Zepbound) pairs GLP-1 with GIP, a different hormone. Mazdutide instead pairs GLP-1 with glucagon, which raises energy burning and acts on the liver, and it is modeled on oxyntomodulin, a natural gut hormone that activates both of those receptors. It does not use GIP.

In the GLORY-1 trial, mazdutide lowered uric acid, the compound behind gout, by more than weight loss alone would usually explain, which is a notable finding. But a drop in a trial is not an approved treatment. Mazdutide is not a urate-lowering or gout drug, it was not studied or approved for that purpose, and no one should use it that way. The uric-acid effect is an interesting signal that may reflect the glucagon action, worth watching but not yet a clinical use.

Like the rest of the class, the main side effects are in the gut: nausea, vomiting, and diarrhea, usually mild to moderate and heaviest during the weeks when the dose is raised, then easing. Because of the glucagon action, mazdutide also nudges heart rate up a little, by about 3 beats per minute at the approved 4 mg and 6 mg doses in the GLORY-1 trial, with larger rises at the higher 9 mg dose that is still under review. The trials did not turn up an unexpected safety problem, though the long-term record is still being built.

Both are GLP-1/glucagon dual agonists, so they share a mechanism. The differences are that mazdutide is approved in China and built on oxyntomodulin, developed as a broad weight-and-diabetes drug, while survodutide is investigational, not approved anywhere, and, though it also has an obesity program, has centered much of its work on MASH, the scarring form of fatty liver disease. They are mechanistic siblings on different paths.

Deep-Dive Questions

Oxyntomodulin is a hormone the gut releases after a meal, and it naturally activates both the GLP-1 and the glucagon receptors, so it already does the two-hormone job that drug designers want. The catch is that natural oxyntomodulin breaks down in the body within minutes, far too fast to be a weekly medicine. Mazdutide is an engineered version, reshaped to resist that breakdown and last about a week while keeping the dual action. The appeal of starting from a natural dual hormone is that the balance between the two receptor effects is one the body itself uses, rather than a ratio picked by combining two separate synthetic pieces. Whether that theoretical elegance produces a better drug in practice is what the trials measure, and mazdutide's results place it as a capable, approved option rather than a class leader on weight.

The glucagon receptor sits on liver cells, and activating it pushes the liver to burn fat and change how it handles several fuels, which is the leading explanation for the liver-fat reduction. Uric acid is made partly in the liver as a byproduct of breaking down purines, the building blocks of DNA and of the energy molecule the cell runs on. The leading explanation, from laboratory and animal studies, is that glucagon signaling changes the liver's purine handling in a way that lowers how much uric acid it produces,<sup>2</sup> which would fit why the drop measured in the human trial looked larger than weight loss alone would predict.<sup>1</sup> This is still being worked out, and it is why researchers find the glucagon arm of these drugs interesting beyond weight. For now it is a mechanism under study rather than a settled clinical tool.

Mazdutide's diabetes evidence comes from a separate set of trials, the DREAMS program, and it was strong enough to earn the China diabetes approval in September 2025. In those trials it lowered A1C, the three-month blood-sugar average, substantially while also driving weight loss, and in one head-to-head study it outperformed semaglutide on blood-sugar control with more weight lost. That head-to-head win matters, because it is a true comparison, unlike the cross-trial figures used for weight. It is important not to stretch that into a claim that mazdutide beats other drugs for weight loss, since those comparisons come from separate trials, but for blood sugar in the studied population, the diabetes data are strong and were enough for approval.

Because retatrutide engages a third receptor. Retatrutide is a triple agonist, hitting GIP, GLP-1, and glucagon, while mazdutide hits two, GLP-1 and glucagon. The broad pattern in this class is that the more of these hunger-and-metabolism receptors a drug engages, and the more fully it engages them, the more weight it tends to produce, which is why the triple agonist reports the highest numbers and the single-hormone drugs the lowest. Mazdutide's roughly 11 to 14% at its approved doses reflects a well-balanced two-receptor drug rather than a maximal one, and its higher 9 mg dose, which reached about 20% in a separate trial, shows the numbers climb with dose, at the cost of more of the side effects that come with pushing these drugs harder.

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