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:

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.

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

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

Sources

1. Ji, L., et al. (2025). Mazdutide in Chinese Adults with Overweight or Obesity (GLORY-1). New England Journal of Medicine. NEJM
2. DREAMS-3 trial results. Mazdutide vs semaglutide 1 mg in type 2 diabetes. Phase 3, 32 weeks.
3. Innovent Biologics. Mazdutide (Xinermei) prescribing information and regulatory filings. Innovent
4. ClinicalTrials.gov: Mazdutide trials
5. 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.