Mazdutide: The Complete Guide

Mazdutide (also known as IBI362 and LY3305677) is a peptide GLP-1 receptor + glucagon receptor dual agonist developed by Eli Lilly and licensed to Innovent Biologics (Suzhou, China) in August 2019 for China rights. Lilly retains ex-China rights but has not announced a US Phase 3 program.

Important correction: some sources (including older StackTrax encyclopedia content) describe mazdutide as a "triple GLP-1/GIP/glucagon agonist." That is wrong. Mazdutide is a DUAL agonist (GLP-1 + glucagon). The triple agonist is retatrutide.

Marketed name in China:

Xinermei — the Innovent commercial product. Sold in China since the 2025 NMPA approvals. Not exported.

Regulatory status (this matters most):

Jurisdiction	Status	Date	Indication
China (NMPA)	Approved	27 June 2025	Chronic weight management (BMI ≥ 28, or ≥ 24 with comorbidity)
China (NMPA)	Approved	September 2025	Glycemic control in adults with type 2 diabetes
United States (FDA)	Not approved — no NDA filed	—	—
European Union (EMA)	Not approved	—	—
UK (MHRA)	Not approved	—	—
Japan (PMDA), Canada (Health Canada)	Not approved	—	—

Practical implication for US users: any mazdutide a US user obtains is research-chemical or smuggled product. There is no legitimate prescription pathway in the United States. Neither Lilly nor Innovent sells the approved Chinese product (Xinermei) outside of China. Mazdutide is not on the FDA 503A bulks list and cannot be lawfully compounded as a sterile injectable.

WADA status:

Not on the 2026 Prohibited List by name. As an unapproved-in-the-US peptide hormone, S0 / S2 catch-all language likely applies. Athletes should consult their governing body.

Mazdutide co-activates two receptors simultaneously:

GLP-1R activation:

• Glucose-dependent insulin secretion from pancreatic β-cells.
• Suppression of glucagon secretion in hyperglycemia.
• Delayed gastric emptying.
• Central appetite suppression via hypothalamic GLP-1R signaling.

This is the same axis as semaglutide.

Glucagon receptor (GCGR) activation:

• Increased hepatic energy expenditure.
• Increased fatty acid oxidation in liver.
• Reduced hepatic lipid accumulation — the source of the large liver-fat reduction signal in trials.
• Some glycogenolysis and gluconeogenesis stimulation (counter-regulatory; the GLP-1R arm normally compensates).

The combination effect:

The glucagon arm drives the liver-fat reduction and metabolic-rate increase that pure GLP-1 RAs don’t produce. The GLP-1 arm drives the appetite suppression and insulin response. Net: comparable or better weight loss and glycemic control than pure GLP-1 RAs, with a particularly notable hepatic-steatosis signature.

This mechanism is distinct from tirzepatide (GLP-1 + GIP) and from retatrutide (GLP-1 + GIP + glucagon). Different receptor combinations produce different downstream clinical signatures.

Unlike most compounds StackTrax audits, mazdutide has a real, large, peer-reviewed Phase 3 record — from China.

Trial	Population	Headline Result	Citation
GLORY-1	Phase 3 obesity, 48 weeks	Mazdutide 6 mg: −14.01% body weight vs +0.30% placebo	NEJM 2025, PMID 40421736
GLORY-2 topline	Phase 3 obesity, 9 mg, 60 weeks	Mean weight loss −18.55%; 44% achieved ≥20% loss; −71.9% liver fat reduction (steatosis subgroup)	Innovent / Lilly press release, 2025
DREAMS-3 (head-to-head vs semaglutide)	Mazdutide 6 mg vs semaglutide 1 mg	HbA1c −2.03% vs −1.84%; weight −10.29% vs −6.00% (mazdutide superior)	Innovent press release
DREAMS-2 / Phase 3 T2DM	Mazdutide for type 2 diabetes	Back-to-back Nature publications	PMIDs 41407859, 41407860
High-dose Phase 1 (16 mg, 20 weeks)	Healthy volunteers / overweight	Mean weight loss −21.0%	PMID 40832785
First Approval review	Drug-history overview	Adis review series	PMID 41028652

The 71.9% liver-fat reduction at 60 weeks is among the largest ever reported for any incretin-class agent. The glucagon-receptor arm is the mechanistic source.

Drug	Receptors	Approval Status	Distinguishing Feature
Semaglutide (Wegovy / Ozempic)	GLP-1R only	FDA + EMA approved	Clinical workhorse; best-studied; weekly
Tirzepatide (Mounjaro / Zepbound)	GLP-1R + GIPR	FDA + EMA approved	Strongest weight loss among approved drugs; weekly
Mazdutide (Xinermei)	GLP-1R + GCGR	NMPA approved 2025; not US/EU	Largest liver-fat reduction signature; weekly
Retatrutide	GLP-1R + GIPR + GCGR	Investigational (Phase 3)	Triple agonist; potentially largest weight loss; weekly

Key disambiguation: mazdutide and retatrutide both activate the glucagon receptor; they are not the same molecule. Mazdutide does not bind GIP. Retatrutide binds all three (GLP-1 + GIP + glucagon).

This is the actual approved Chinese-label dosing. For US users without a legitimate prescription pathway, this is the closest thing to a validated dose.

Obesity (NMPA approved June 2025):

• Starting dose: 2 mg once weekly SC
• Escalate to 4 mg weekly after 4 weeks
• Optional further escalation to 6 mg weekly after another 4 weeks at 4 mg
• Higher doses (9 mg) under supplementary application

Type 2 diabetes (NMPA approved September 2025):

• Same titration; commonly maintained at 4–6 mg weekly

Route:

Subcutaneous, once weekly. Standard incretin-class injection sites (abdomen, thigh, upper arm).

Half-life:

Compatible with weekly dosing (specific human PK numbers in the published trial publications — see the Phase 1 PMIDs above).

Mazdutide’s safety profile in published trials is broadly similar to other incretin-class drugs, with some glucagon-receptor-related distinctives.

Common (incretin class):

• GI: nausea, vomiting, diarrhea, constipation. Most pronounced during dose escalation; typically improves with continued exposure.
• Decreased appetite — the on-target effect.
• Injection-site reactions — transient redness, mild itching.
• Hypoglycemia — uncommon as monotherapy; risk increases with concurrent insulin or sulfonylureas.

Class concerns (incretin / GLP-1R class):

• Pancreatitis — class concern; specific incidence in mazdutide trials per the published reports.
• Thyroid C-cell tumors — class boxed warning for GLP-1 RAs based on rodent data; relevance to humans debated.
• Gallbladder disease — class concern; rapid weight loss is a risk factor.

Glucagon-receptor-arm-specific considerations:

• Possible cardiovascular effects from glucagon receptor activation — published trial reports characterize the cardiovascular signature.
• Counter-regulatory glucose effects — mostly compensated by the GLP-1R arm in the dual-agonist context.

• Personal or family history of medullary thyroid carcinoma (MTC) — class boxed warning.
• Multiple endocrine neoplasia type 2 (MEN-2) — class boxed warning.
• History of pancreatitis — relative contraindication; specialist sign-off.
• Pregnancy / breastfeeding — class concern; not studied.
• Active gallbladder disease — relative caution.
• Severe gastroparesis — class concern.
• Type 1 diabetes — not a substitute for insulin.
• Concurrent insulin or sulfonylureas — hypoglycemia risk; physician supervision required.

• Semaglutide — pure GLP-1R agonist. Different receptor profile; smaller liver-fat reduction.
• Tirzepatide — GLP-1R + GIPR (not glucagon). Different mechanism, different liver-fat profile.
• Retatrutide — GLP-1R + GIPR + GCGR (TRIPLE agonist, not dual). Different molecule.
• Survodutide (BI 456906) — Boehringer/Zealand GLP-1/glucagon dual agonist (same receptor profile as mazdutide). In Phase 3; not yet approved anywhere as of 2026-05.
• Liraglutide (Saxenda / Victoza) — daily GLP-1R agonist; older generation.
• Cotadutide — AstraZeneca GLP-1/glucagon dual agonist (same receptor profile); development stalled.