Investigational · not FDA approved

Editorially reviewed · Last updated February 2026 · How we review

What Is Mazdutide (Xinermei)? The First GLP-1/Glucagon Drug Approved in China

Mazdutide is a dual GLP-1 and glucagon receptor agonist developed by Innovent Biologics, based on a molecule originally discovered by Eli Lilly. It is a once-weekly subcutaneous injection that activates two hormone receptors simultaneously: GLP-1 to suppress appetite and glucagon to increase energy expenditure and promote liver fat oxidation.

Mazdutide is approved in China under the brand name Xinermei — for obesity (June 2025) and type 2 diabetes (September 2025). It is not approved by the FDA or any other Western regulatory agency. US Phase 2 trials are ongoing, with no established timeline for FDA submission.

What makes mazdutide distinctive in the current obesity drug landscape is its glucagon component. Unlike semaglutide (GLP-1 only) or tirzepatide (GLP-1 + GIP), mazdutide pairs GLP-1 with glucagon — a receptor that directly drives liver fat breakdown and thermogenesis. It shares this glucagon element with retatrutide, Eli Lilly's investigational triple agonist, though retatrutide adds a third receptor (GIP) on top.

How Mazdutide Works

Mazdutide is a single-molecule dual agonist that activates two distinct receptor pathways. Each receptor contributes a different mechanism to weight loss and metabolic improvement.

GLP-1 Receptor: Appetite Suppression

The GLP-1 (glucagon-like peptide-1) receptor is the same target used by semaglutide (Ozempic/Wegovy) and tirzepatide (Mounjaro/Zepbound). When activated, it:

Reduces appetite by acting on brain regions that control hunger and satiety
Slows gastric emptying, prolonging the feeling of fullness after eating
Improves insulin secretion in a glucose-dependent manner, lowering blood sugar
Suppresses glucagon release from the pancreas after meals

This is the well-established mechanism behind the entire GLP-1 drug class. Mazdutide's GLP-1 activity provides the core appetite-suppressing effect.

Glucagon Receptor: Energy Expenditure and Liver Fat Oxidation

The glucagon receptor is what distinguishes mazdutide from GLP-1-only drugs. Glucagon is a catabolic hormone that acts primarily on the liver. When the glucagon receptor is activated, it:

Promotes hepatic fat oxidation — the liver directly breaks down stored fat at an accelerated rate
Increases energy expenditure through thermogenesis
Stimulates lipolysis — the breakdown of fat in adipose tissue
Activates gluconeogenesis — the liver produces glucose from non-carbohydrate sources

The glucagon component is why mazdutide (and retatrutide) show dramatically better liver fat reduction than GLP-1-only drugs. It directly targets the organ where metabolic dysfunction-associated steatotic liver disease (MASLD) occurs.

What Mazdutide Does Not Target: GIP

Notably, mazdutide does not activate the GIP (glucose-dependent insulinotropic polypeptide) receptor. This is the third receptor targeted by tirzepatide and retatrutide. GIP complements GLP-1 by enhancing insulin secretion and may have additional effects on fat metabolism.

The absence of GIP agonism means mazdutide takes a different strategic approach: appetite suppression (GLP-1) plus metabolic activation (glucagon), rather than the enhanced incretin signaling (GLP-1 + GIP) used by tirzepatide or the three-pronged approach (GLP-1 + GIP + glucagon) used by retatrutide.

Clinical Trial Data

GLORY-1 (Phase 3 — Obesity)

The GLORY-1 trial was a Phase 3, randomized, double-blind, placebo-controlled study published in the New England Journal of Medicine. It enrolled 610 Chinese adults with obesity (BMI 28 or above) or overweight (BMI 24 or above) with at least one weight-related comorbidity. Results at 48 weeks:

Dose	Weight Loss at 48 Weeks
Mazdutide 4 mg	-11.00%
Mazdutide 6 mg	-14.01%
Placebo	-1.12%

The discontinuation rate was remarkably low: 0.5-1.5% across both dose levels. This is the lowest reported discontinuation rate among all GLP-1-class drugs in Phase 3 obesity trials, suggesting excellent tolerability.

DREAMS-3 (Phase 3 — Type 2 Diabetes)

The DREAMS-3 trial is notable because it included a head-to-head comparison against semaglutide. It compared mazdutide 6 mg versus semaglutide 1 mg in adults with type 2 diabetes over 32 weeks.

Outcome	Mazdutide 6 mg	Semaglutide 1 mg
Primary composite (HbA1c under 7% + 10%+ weight loss)	48%	21%
HbA1c reduction	-2.03%	-1.84%
Weight loss	-10.29%	-6.00%

Mazdutide outperformed semaglutide 1 mg on both glycemic control and weight loss. Note that this trial used semaglutide 1 mg, not the maximum approved dose for diabetes (2 mg for Ozempic), so the comparison has limitations.

MASLD Substudy (Phase 2 — Liver Fat)

In a Phase 2 substudy focused on metabolic dysfunction-associated steatotic liver disease (MASLD), mazdutide produced 73-80% liver fat reduction. This is far beyond what GLP-1-only drugs achieve (typically 40-50%) and is directly attributable to the glucagon receptor component driving hepatic fat oxidation.

For context, retatrutide showed 82-86% liver fat reduction in its Phase 2 trial — in the same range, consistent with the shared glucagon mechanism.

Side Effects

Mazdutide's side effect profile is broadly consistent with other GLP-1-class drugs: gastrointestinal symptoms are the most common adverse events, concentrated during the dose escalation period.

The most frequently reported side effects include:

Nausea (the most common, typically mild and transient)
Diarrhea
Decreased appetite
Vomiting (less common than nausea)

Tolerability: Best in Class

What stands out about mazdutide is not the type of side effects, but the discontinuation rate. In GLORY-1, only 0.5-1.5% of participants stopped treatment due to adverse events. For comparison:

Semaglutide 2.4 mg (STEP 1): approximately 7% discontinued due to adverse events
Tirzepatide (SURMOUNT-1): approximately 4-7% across dose groups

This very low discontinuation rate suggests that mazdutide's side effects are generally mild enough that almost all patients can tolerate the full treatment course. The gradual titration schedule likely contributes to this tolerability.

No unique safety signals (beyond the standard GI profile) have been reported in mazdutide's published trial data. However, retatrutide — which also contains glucagon receptor activity — has shown a dysesthesia signal (tingling/burning sensation). Whether mazdutide produces a similar effect at higher doses or in larger populations remains to be determined.

How Mazdutide Compares to Other Weight Loss Drugs

	Mazdutide	Semaglutide	Tirzepatide	Retatrutide
Drug class	Dual GLP-1/Glucagon agonist	GLP-1 agonist	Dual GLP-1/GIP agonist	Triple GLP-1/GIP/Glucagon agonist
Receptors	GLP-1 + Glucagon	GLP-1	GLP-1 + GIP	GLP-1 + GIP + Glucagon
Developer	Innovent Biologics (molecule from Eli Lilly)	Novo Nordisk	Eli Lilly	Eli Lilly
Max weight loss (trials)	-14.01% (GLORY-1, 6 mg, 48 wks)	-16.9% (STEP 1, 68 wks)	-22.5% (SURMOUNT-1, 72 wks)	-28.7% (TRIUMPH-4, 12 mg, 68 wks)
Max HbA1c reduction	-2.03% (DREAMS-3)	~-1.8% (SUSTAIN)	~-2.4% (SURPASS)	-2.02% (Phase 2)
Liver fat reduction	73-80%	~40-50%	~50-55%	82-86%
Dosing	Once weekly injection	Once weekly injection	Once weekly injection	Once weekly injection
Max dose tested	6 mg	2.4 mg (obesity)	15 mg	12 mg
Discontinuation (adverse events)	0.5-1.5%	~7%	~4-7%	Standard for class
Approval status	Approved in China (Xinermei). Not FDA approved.	FDA approved (Wegovy 2021)	FDA approved (Zepbound 2023)	Phase 3 trials (not approved anywhere)

The comparison highlights mazdutide's position as a middle-ground drug: stronger liver fat reduction than semaglutide or tirzepatide (thanks to the glucagon component), with notably better tolerability, but lower absolute weight loss than either tirzepatide or retatrutide. Different trial populations and durations make direct comparison imprecise.

Mazdutide vs Retatrutide

Mazdutide and retatrutide share glucagon receptor agonism, but they diverge from there. Retatrutide is a triple agonist (GLP-1 + GIP + glucagon) while mazdutide is a dual agonist (GLP-1 + glucagon, no GIP).

In published trials, retatrutide has produced greater absolute weight loss (28.7% vs 14.01%), though these numbers come from different populations, durations, and maximum doses. Both drugs show similarly strong liver fat reduction (73-86%), consistent with their shared glucagon mechanism.

The two drugs also have different development trajectories: mazdutide is already approved and available in China, while retatrutide is not approved anywhere and is still in Phase 3 trials.

For a detailed side-by-side breakdown, see Retatrutide vs Mazdutide: Dual Agonist vs Triple Agonist Compared.

Current Status and Availability

Approved in China

Mazdutide is approved in China under the brand name Xinermei, manufactured by Innovent Biologics:

June 2025: Approved by China's National Medical Products Administration (NMPA) for chronic weight management in adults with obesity or overweight with comorbidities
September 2025: Approved in China for type 2 diabetes

Not Available in the US or Europe

Mazdutide is not approved by the FDA, the European Medicines Agency, or any regulatory body outside China. US Phase 2 trials are ongoing. No FDA submission timeline has been established, and it would be several years before US availability even under an optimistic scenario.

The Eli Lilly Connection

The mazdutide molecule was originally discovered by Eli Lilly and licensed to Innovent Biologics for development in the China market. Eli Lilly separately developed retatrutide as its own next-generation obesity drug for global markets. The two drugs share a corporate lineage but are structurally distinct compounds with different receptor profiles.

Frequently Asked Questions

What is mazdutide?

Mazdutide is a dual GLP-1 and glucagon receptor agonist developed by Innovent Biologics (originally discovered by Eli Lilly). It is a once-weekly injectable drug that suppresses appetite through GLP-1 and increases energy expenditure and liver fat oxidation through glucagon receptor activation. It is approved in China under the brand name Xinermei.

Is mazdutide FDA approved?

No. Mazdutide is approved only in China (for obesity and type 2 diabetes). It is not approved by the FDA or any European regulatory agency. US Phase 2 trials are ongoing, with no established timeline for FDA submission.

How much weight can you lose on mazdutide?

In the GLORY-1 Phase 3 trial, mazdutide 6 mg produced 14.01% body weight loss at 48 weeks in Chinese adults with obesity. The 4 mg dose produced 11.00% weight loss. These results are from a Chinese population and may differ in other demographics.

What is the difference between mazdutide and semaglutide?

Semaglutide targets only the GLP-1 receptor. Mazdutide targets both GLP-1 and glucagon receptors. The glucagon component gives mazdutide significantly stronger liver fat reduction (73-80% vs approximately 40-50% for semaglutide) and may increase energy expenditure. In the DREAMS-3 head-to-head trial, mazdutide 6 mg outperformed semaglutide 1 mg on both weight loss and HbA1c reduction.

What is the difference between mazdutide and tirzepatide?

Tirzepatide (Mounjaro/Zepbound) targets GLP-1 and GIP receptors. Mazdutide targets GLP-1 and glucagon receptors. They activate completely different second receptors. Tirzepatide has produced greater weight loss in trials (up to 22.5%), while mazdutide shows stronger liver fat reduction due to its glucagon component.

What is the difference between mazdutide and retatrutide?

Retatrutide is a triple agonist targeting GLP-1, GIP, and glucagon. Mazdutide is a dual agonist targeting GLP-1 and glucagon (no GIP). Both share the glucagon component that drives liver fat reduction. Retatrutide has shown greater weight loss (28.7% vs 14.01%), though the trials differed in population, duration, and dosing. See our full retatrutide vs mazdutide comparison.

Where can I get mazdutide?

Mazdutide (brand name Xinermei) is available by prescription in China for obesity and type 2 diabetes. It is not available in the United States, Europe, or other markets outside China. There is no established timeline for availability in Western countries.

Is mazdutide good for fatty liver disease?

Mazdutide has shown 73-80% liver fat reduction in a Phase 2 MASLD substudy, far exceeding what GLP-1-only drugs achieve. This is directly attributed to the glucagon receptor component, which promotes hepatic fat oxidation. Larger trials specifically studying mazdutide in liver disease are ongoing.

Sources

Ji, L., et al. (2025). Mazdutide in Chinese Adults with Overweight or Obesity (GLORY-1). New England Journal of Medicine. NEJM
DREAMS-3 trial results. Mazdutide vs semaglutide 1 mg in type 2 diabetes. Phase 3, 32 weeks.
Innovent Biologics. Mazdutide (Xinermei) prescribing information and regulatory filings. Innovent
ClinicalTrials.gov: Mazdutide trials
Jastreboff, A.M., et al. (2023). Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. New England Journal of Medicine. DOI: 10.1056/NEJMoa2301972

This article is for informational purposes only and does not constitute medical advice. Mazdutide (Xinermei) is approved in China but is not approved by the U.S. Food and Drug Administration (FDA). Always consult a healthcare provider before starting any medication. This site is not affiliated with Innovent Biologics, Eli Lilly, or any pharmaceutical manufacturer.

How we keep this honest

What this is: Educational information, not medical advice. It reports published research — it doesn’t recommend that you use, obtain, or supply anything.
Regulatory status: Retatrutide and similar peptides are investigational — not approved by the FDA or any regulator. Semaglutide and tirzepatide are prescription-only medicines, available only through a licensed prescriber.
Our standard: Every claim traces to a primary source. We label the strength of evidence and flag estimates as estimates — never as clinical fact.
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Do not make decisions about your health without consulting a qualified healthcare provider. For trial enrolment, see ClinicalTrials.gov. More on how we review.

Sources