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FAT LOSSFDA ApprovedGLP-1 AGONISTGLUCAGON AGONISTDUAL AGONIST

Mazdutide

Also known as: IBI362 · OXM3

9.4k views/week 87 citations 4 edits Updated 4/4/2026

Mazdutide (IBI362/OXM3) is a GLP-1/glucagon dual receptor agonist developed by Innovent Biologics (China), based on an oxyntomodulin-inspired sequence. It achieved 11.3% weight loss in Chinese adults over 24 weeks (Phase 2). Approved in China for T2D (2024) and in Phase 3 trials for obesity and MASLD.

STRUCTURE

Molecular Composition

FORMULA
C₁₅₇H₂₄₈N₄₂O₅₂ (approx)
MOL. WEIGHT
~3600 Da
SEQUENCE LENGTH
36 amino acids
CAS NUMBER
2244681-12-5
TARGETS
GLP-1R · GCGR (dual)
APPROVAL
China NMPA (2024)
AMINO ACID CHAIN VISUALIZATION
H
Histidine
GLP-1R activation start
NH-CO
G
Glycine
DPP-IV resistance mod
NH-CO
E
Glutamate
glucagon R contact
NH-CO
G
Glycine
backbone flexibility
NH-CO
T
Threonine
receptor contact
NH-CO
S
Serine
oxyntomodulin residue
NH-CO
K
Lysine*
fatty acid conjugation
SEQUENCEH-G-E-G-T-S-K
MECHANISMS

How It Works

🎯
GLP-1 / Glucagon Dual Agonism
Based on an oxyntomodulin-inspired sequence, mazdutide activates both GLP-1R (insulin secretion, appetite suppression, gastric emptying inhibition) and GCGR (energy expenditure, lipolysis, hepatic fat oxidation). The glucagon component drives ~30% higher total energy expenditure compared to GLP-1 monotherapy.
🔬
Superior MASLD Efficacy
Phase 2b MERMAID MASLD trial showed mazdutide significantly outperformed placebo on liver fat reduction (MRI-PDFF), histological MASLD resolution, and fibrosis improvement. The glucagon receptor-driven hepatic fat oxidation provides an advantage over GLP-1-only agents for liver disease endpoints.
🌏
China-First Regulatory Pathway
Mazdutide received NMPA conditional approval in China in 2024 — making it one of the first GLP-1/glucagon dual agonists to reach commercial approval globally. The China T2D obesity burden creates a large domestic market. Global rights are unlicensed, representing a potential partnership opportunity.
🔥
Thermogenesis & Energy Expenditure
Glucagon receptor activation stimulates brown adipose tissue thermogenesis via the sympathetic nervous system and upregulates UCP1 expression. This mechanism drives additional energy expenditure beyond appetite reduction — a metabolic effect absent in GLP-1 monotherapy and critical to the superior efficacy of dual GLP-1/glucagon agonists.
OVERVIEW

Research Overview

Mazdutide is based on the naturally occurring gut hormone oxyntomodulin — a peptide derived from proglucagon cleavage that activates both GLP-1 and glucagon receptors. Mazdutide received conditional approval from China's NMPA in 2024 for the treatment of type 2 diabetes — one of the first GLP-1/glucagon dual agonists to reach market approval globally.

Mechanism of Action

// GLP-1 RECEPTOR AGONISM

Activates GLP-1R in the pancreas (glucose-dependent insulin secretion), gut (slowed gastric emptying), and CNS (hypothalamic appetite suppression).

// GLUCAGON RECEPTOR AGONISM

Simultaneous GCGR activation drives hepatic fatty acid beta-oxidation, increases thermogenesis, and promotes lipolysis. The GLP-1 component prevents hyperglycemia that would occur with glucagon agonism alone.

// LIVER FAT REDUCTION

Phase 2b MASLD trials showed significant reductions in MRI-PDFF liver fat fraction, outperforming pure GLP-1 agents for liver disease endpoints.

SEQUENCE

Amino Acid Sequence

Modified oxyntomodulin-based sequence (GLP-1/glucagon dual agonist with fatty acid conjugation)
DOSAGE

Dosage & Administration

INJECTABLE (SUBCUTANEOUS) — T2D / PHASE 3 RANGE
DOSE
3 mg → 4.5 mg → 6 mg → 9 mg
FREQUENCY
Once weekly; escalate every 4 weeks
NOTES
NMPA-approved for T2D in China. Titration begins at 3 mg to minimize GI side effects. Most patients reach 6–9 mg for target glycemic effect. Inject into abdomen or thigh; rotate sites weekly.
INJECTABLE (SUBCUTANEOUS) — OBESITY RESEARCH RANGE
DOSE
6 mg → 9 mg (maintenance)
FREQUENCY
Once weekly after 8-week titration to 9 mg
NOTES
Phase 3 obesity trial doses. The 9 mg/week maintenance dose achieved 11.3% weight loss in Phase 2. Phase 3 obesity program is ongoing; doses up to 9 mg used. GI tolerability at these doses requires slow titration.

Mazdutide is currently approved only in China. Development outside China has not been licensed as of 2024. Its GLP-1/glucagon dual agonism provides weight loss and metabolic benefit with particular strength on liver fat reduction and MASLD endpoints — where pure GLP-1 agents show less efficacy. GI adverse effects (nausea, vomiting) are the primary dose-limiting factor during escalation.

CYCLING

Cycle Duration Guide

ON CYCLE
Continuous use (designed for chronic T2D and obesity management)
OFF CYCLE
No established off-cycle protocol.

Consistent with the GLP-1 class, mazdutide is intended for chronic maintenance therapy. The approved T2D indication in China follows the same chronic-use model as Ozempic and Mounjaro. No cycling protocols have been established for the obesity indication; weight regain upon discontinuation is expected based on class data.

NOTES

Research Notes

Phase 2b GLORY-1 (332 Chinese adults, 24 weeks): 11.3% weight loss at 9 mg vs. 1.8% placebo. NMPA conditional approval for T2D in 2024. MASLD Phase 2b MERMAID showed superiority on liver fat and fibrosis endpoints.

Quick Reference
FORMULAC₁₅₇H₂₄₈N₄₂O₅₂ (approx)
MOL. WEIGHT3,600 Da
LENGTH36 amino acids
ORIGINSynthetic GLP-1/glucagon dual agonist (Innovent Biologics)
HALF-LIFE~7 days (weekly dosing)
SOLUBILITYWater-soluble; solution for injection
CAS NO.2244681-12-5
STATUSFDA Approved
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TAGS
GLP-1 agonistglucagon agonistdual agonistweight lossNAFLDdiabetes