Mazdutide: China's GLP-1/Glucagon Dual Agonist for Obesity

Mazdutide (development code IBI362, brand name Xinerda in China) became the world's first approved GLP-1/glucagon dual receptor agonist for weight management when China's National Medical Products Administration cleared it in June 2025. A second approval for glycemic control in type 2 diabetes followed in September 2025. Both decisions rested on the GLORY-1 and DREAMS phase 3 programs — and GLORY-1, published in the New England Journal of Medicine, made mazdutide the first Chinese-developed obesity drug to land in that journal.

The drug matters for two reasons. The mechanism — adding glucagon receptor activation on top of GLP-1 — produces weight loss in a different way than semaglutide or tirzepatide, with knock-on effects on liver fat that are unusually large even by the standards of the current obesity drug pipeline. And a head-to-head phase 3 trial against semaglutide reported superior glycemic-plus-weight outcomes, which is the first time any dual agonist has beaten the GLP-1 standard of care on a combined endpoint in late-stage data.

This is what the published evidence shows, how mazdutide compares with the GLP-1 medications already on the U.S. market, and what its China-first approval pathway means for patients outside that market.

What Mazdutide Is

Mazdutide is a synthetic peptide engineered from oxyntomodulin, the gut hormone that naturally activates both the GLP-1 and glucagon receptors after meals. The peptide is conjugated to a fatty acid chain — the same albumin-binding strategy used in semaglutide and tirzepatide — which extends its half-life enough to support once-weekly subcutaneous injection.

Innovent Biologics licensed the molecule from Eli Lilly in 2019 and has run all of its pivotal trials in Chinese adults. The approved indications and doses are:

Indication	Maintenance Dose	Approval Date
Weight management (BMI ≥ 28, or ≥ 24 with comorbidity)	4 mg or 6 mg weekly	June 2025 (China NMPA)
Type 2 diabetes glycemic control	4 mg or 6 mg weekly	September 2025 (China NMPA)

Phase 3 trials of higher doses (9 mg in GLORY-2, head-to-head 6 mg vs semaglutide in DREAMS-3 and GLORY-3) are running concurrently, so the approved doses are not the ceiling of clinical use even within China.

How the Glucagon Arm Changes the Pharmacology

GLP-1 receptor agonism is the well-understood half of the molecule: delayed gastric emptying, central appetite suppression, and glucose-dependent insulin release. The glucagon receptor agonism is the part that distinguishes mazdutide from tirzepatide, retatrutide, and every approved GLP-1 monotherapy.

Hepatic glucagon receptor activation raises energy expenditure through fatty-acid oxidation and thermogenic pathways, mobilizes triglycerides out of the liver, and increases the rate at which substrate is burned rather than stored. The trade-off is that glucagon also raises hepatic glucose output — which is exactly why pure glucagon agonists fail as diabetes drugs. The dual-agonist trick is to tune the ratio so the GLP-1 arm's insulin-secreting and glucagon-suppressing effects dominate at the level of glycemia, while the glucagon arm's metabolic-rate effects show up in body composition and liver fat.

Evidence: "Mazdutide is a synthetic peptide that activates both the GLP-1 receptor and glucagon receptor… simultaneous activation of GCGR on the basis of GLP-1R agonism may confer greater benefits on liver fat reduction." — Ji L, et al. eClinicalMedicine. 2022. 10.1016/j.eclinm.2022.101691

The clinical signature of that tuning, visible across every mazdutide trial, is disproportionate visceral and hepatic fat loss relative to total weight loss, plus measurable improvements in lipid handling that go beyond what pure GLP-1 activity explains.

GLORY-1: The Pivotal Obesity Trial

GLORY-1 was a 48-week, randomized, double-blind, placebo-controlled phase 3 trial in 610 Chinese adults with obesity (BMI ≥ 28 kg/m²) or overweight (BMI ≥ 24 with at least one comorbidity). Participants were randomized to weekly subcutaneous mazdutide 4 mg, mazdutide 6 mg, or placebo, with co-primary endpoints at week 32.

At week 48, the placebo-corrected weight reductions were:

Group	Mean Weight Change	≥ 5% Loss	≥ 15% Loss
Mazdutide 4 mg	–11.0%	~74%	~24%
Mazdutide 6 mg	–14.0%	~82%	~36%
Placebo	–0.3%	~10%	~1%

The 6 mg arm hit a placebo-adjusted weight loss of roughly 13.7% — in the same range as semaglutide 2.4 mg at 68 weeks in the STEP-1 trial, achieved 20 weeks sooner. The weight curve was still descending at week 48, which is a recurring pattern with this class and suggests the plateau lies beyond the trial endpoint.

Evidence: "Once-weekly mazdutide at 4-mg and 6-mg doses resulted in significant weight loss as compared with placebo in Chinese adults with obesity or overweight." — Ji L, Jiang H, et al. N Engl J Med. 2025;392:2215–2225. 10.1056/NEJMoa2411528

What stood out beyond the headline number was the secondary metabolic data. Waist circumference, blood pressure, triglycerides, ALT, AST, and uric acid all improved in the active arms versus placebo — and the magnitude of triglyceride and liver enzyme reduction outpaced what pure GLP-1 agonists typically deliver at comparable weight loss.

The Liver Fat Result

A pre-specified MRI-PDFF substudy of GLORY-1 enrolled the 69 participants with baseline liver fat content ≥ 5% who had paired imaging at week 48. The result was striking: mazdutide 6 mg produced a mean 80.2% relative reduction in liver fat content, with the 4 mg group not far behind. More than 80% of participants on the active doses achieved liver fat normalization (LFC < 5%) by week 48.

That is the largest hepatic fat reduction reported for any obesity drug at this stage of development, and it is consistent with the mechanistic prediction: the glucagon receptor arm is doing work the GLP-1 arm cannot. For patients with metabolic dysfunction-associated steatotic liver disease (MASLD) — which affects roughly 40% of adults with obesity — that result is what shifts mazdutide from "another weight-loss drug" to a candidate with a distinct therapeutic identity.

The dedicated GLORY-3 trial, comparing mazdutide head-to-head against semaglutide in adults with obesity and fatty liver disease, started dosing in late 2025. Those data will determine whether the liver-fat advantage holds up against semaglutide on matched weight loss.

Mazdutide in Type 2 Diabetes

The DREAMS-1 and DREAMS-2 trials, published back-to-back in Nature in December 2025, established mazdutide's glycemic profile in Chinese adults with type 2 diabetes.

DREAMS-1 randomized treatment-naïve T2D patients to mazdutide 4 mg, 6 mg, or placebo over 24 weeks. Both doses produced HbA1c reductions of roughly 1.6–1.9 percentage points, alongside 5–8% body weight loss — without an increased risk of hypoglycemia, which is the safety reassurance most relevant to clinicians considering a glucagon-active molecule in diabetic patients.

Evidence: "Mazdutide significantly improved glycaemic control and reduced body weight in Chinese adults with type 2 diabetes, with a safety profile consistent with the GLP-1 receptor agonist class." — Zhu D, Zhao J, et al. Nature. 2026;652:174–180. 10.1038/s41586-025-10026-w

The earlier phase 2 program had already shown the dual mechanism at work: at 20 weeks, mazdutide 4.5 mg produced HbA1c reductions of around 1.7%, weight loss of 6.5%, and improvements in fasting and postprandial glucose that exceeded what comparable GLP-1 monotherapy produces at similar weight loss.

Evidence: "Mazdutide was effective in glycaemic control and weight loss in Chinese patients with type 2 diabetes inadequately controlled with diet and exercise, with a safety profile in line with other GLP-1 receptor agonists." — Zhang B, Cheng Z, et al. Diabetes Care. 2024;47(1):160–168. 10.2337/dc23-1287

DREAMS-3 went further. It is the first head-to-head phase 3 trial of a dual GLP-1/glucagon agonist against semaglutide in type 2 diabetes complicated by obesity. At 32 weeks, mazdutide met its primary endpoint: 48% of mazdutide patients achieved both HbA1c < 7.0% and ≥ 10% weight loss, versus 21% on semaglutide (p < 0.0001). DREAMS-3 has been presented but not yet published in full, so the field is waiting for the manuscript-level data before drawing comparisons to Ozempic and Wegovy outside the Chinese population.

Safety and Tolerability

The adverse-event profile across phase 1b, phase 2, and the GLORY/DREAMS phase 3 trials is recognizably GLP-1-class — gastrointestinal symptoms during dose escalation, fading at maintenance:

Nausea: 20–30% during titration, mostly mild-to-moderate
Diarrhea: ~25–35%, dose-dependent
Vomiting: ~15%, transient
Decreased appetite: common and expected
Treatment-related discontinuations: ~1–2% in GLORY-1 at maintenance

No new safety signals specific to glucagon receptor agonism — no signals of clinically meaningful blood glucose elevation in non-diabetic participants, no rebound dyslipidemia, no hepatotoxicity — have emerged through phase 3. Heart rate increases of 3–5 bpm on average were observed, similar to other GLP-1 agonists. Long-term cardiovascular outcomes data are not yet available; an MACE outcomes trial would be required for U.S. or European labeling.

The discontinuation profile in GLORY-1 is the most quantitatively useful comparison point: roughly 1.5% on 4 mg and 0.5% on 6 mg stopped treatment due to adverse events, which is at the favorable end of the GLP-1 class.

Mazdutide vs Semaglutide vs Tirzepatide

For patients comparing options, the relevant mental model is not "mazdutide replaces what you have" but "mazdutide occupies a third mechanistic position":

	Semaglutide	Tirzepatide	Mazdutide
Mechanism	GLP-1 agonist	GLP-1 + GIP agonist	GLP-1 + glucagon agonist
Phase 3 weight loss (obesity)	~15% (68 wk)	~21% (72 wk)	~14% at 6 mg / up to 20% at 9 mg (48 wk)
Hepatic fat reduction (relative)	~30–40%	~50–70%	~80%
Approval status	Global	Global	China only
Once-weekly dosing	Yes	Yes	Yes

The 9 mg arm in GLORY-2 (reported but not yet peer-reviewed in full) reached up to 20.1% mean weight loss at 48 weeks, which would place mazdutide on a par with tirzepatide for total weight reduction while retaining the larger liver-fat effect. Whether 9 mg becomes the standard maintenance dose, or remains a higher-titration option, will depend on tolerability data in the full publication.

The Global Approval Question

Mazdutide's regulatory status outside China is the practical bottleneck. Innovent has not filed with the FDA or EMA, and the entire phase 3 dataset is in Chinese populations — which complicates direct extrapolation given known differences in average BMI, body composition, and diabetes phenotype between Chinese and Western cohorts. The drug is therefore not available by prescription in the U.S., the U.K., the EU, Canada, or Australia, and patients should be skeptical of any source advertising "mazdutide" outside China through compounding pharmacies or research-peptide vendors. Those products are not the licensed drug and carry the same risks as any unlicensed peptide.

A global development program — phase 3 trials run in non-Chinese populations and submitted to Western regulators — would be required for approval outside China. Innovent has indicated such trials are planned but has not given a public timeline; a realistic earliest approval window in the U.S. or EU is 2028–2029 if multinational phase 3 starts in 2026.

Key Takeaways

Mazdutide is the world's first approved GLP-1/glucagon dual receptor agonist, cleared by China's NMPA in June 2025 for weight management and in September 2025 for type 2 diabetes.
The GLORY-1 phase 3 trial (NEJM 2025) produced 14% weight loss at the 6 mg dose over 48 weeks, with an 80% relative reduction in liver fat content in the MASLD substudy — a hepatic effect that exceeds any other approved GLP-1 medication.
DREAMS-3, a head-to-head phase 3 vs semaglutide in T2D plus obesity, reported a 48% vs 21% advantage on the combined HbA1c-plus-weight endpoint, though the full publication is still pending.
Safety is consistent with the GLP-1 receptor agonist class; the added glucagon mechanism has not introduced new clinical safety signals through phase 3.
The drug is not available outside China. Patients in the U.S., U.K., EU, and other markets should not pursue compounded or research-peptide versions; an FDA-quality multinational program is years away.

References

Ji L, Jiang H, Cai X, et al. Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight. N Engl J Med. 2025;392(22):2215–2225. DOI: 10.1056/NEJMoa2411528
Zhu D, Zhao J, Cai H, et al. Mazdutide versus placebo in Chinese adults with type 2 diabetes. Nature. 2026;652(8108):174–180. DOI: 10.1038/s41586-025-10026-w — PMID: 41407859
Zhang B, Cheng Z, Chen J, et al. Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial. Diabetes Care. 2024;47(1):160–168. DOI: 10.2337/dc23-1287 — PMID: 37943529
Ji L, Gao L, Jiang H, et al. Safety and efficacy of a GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple-ascending-dose phase 1b trial. eClinicalMedicine. 2022;54:101691. DOI: 10.1016/j.eclinm.2022.101691 — PMC9561728
Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989–1002. DOI: 10.1056/NEJMoa2032183
Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205–216. DOI: 10.1056/NEJMoa2206038

Last updated: 2026-05-19 Medical review: Dr. James Chen, MD, PhD, FACE