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Mezdutide

Mezdutide (Mazdutide, IBI362): A GLP-1/Glucagon Dual Receptor Agonist in Late-Stage Metabolic Research

Research summary. Mezdutide (also written mazdutide; development codes IBI362, OXM3) is an investigational dual agonist peptide that activates both the glucagon-like peptide-1 (GLP-1) receptor and the glucagon receptor. It is being developed by Innovent Biologics, originally licensed from Eli Lilly's oxyntomodulin-analogue programme. Within the broader GLP-1-class incretin landscape, mezdutide sits in the "twincretin" or dual-agonist subclass alongside survodutide and pemvidutide — distinct from pure GLP-1 receptor agonists (semaglutide, liraglutide) and from GLP-1/GIP dual agonists (tirzepatide). Late-stage Phase 3 trials in obesity and type 2 diabetes are concentrated primarily in the Chinese clinical development programme.

Molecular profile

  • Sequence: Long-acting oxyntomodulin analogue with lipid-conjugation strategy for albumin binding (full sequence published in development literature)
  • Molecular formula: approximately C₁₇₉H₂₈₈N₅₀O₅₂ (without lipid-modifier specification)
  • Molecular weight: ~3998.6 g/mol
  • Synonyms: Mazdutide, IBI362, OXM3
  • Class: GLP-1 receptor / glucagon receptor dual agonist (oxyntomodulin-class)

Mechanism of action

Mezdutide is engineered to combine two complementary metabolic activities in a single molecule:

  • GLP-1 receptor agonism drives glucose-dependent insulin secretion, slows gastric emptying, and reduces appetite via central pathways — the core mechanism shared with all incretin-class agents.
  • Glucagon receptor agonism increases hepatic energy expenditure, supports fatty-acid oxidation, and contributes to liver-fat reduction. Glucagon agonism is the differentiating feature distinguishing this subclass from pure GLP-1 agents and from GLP-1/GIP dual agonists.

The hypothesis underlying dual-agonist development is that the catabolic activity contributed by glucagon-receptor signalling can produce greater weight loss and greater hepatic-fat reduction than GLP-1 monotherapy at matched tolerability, with the balance of agonism tuned to favour weight loss while limiting glucagon-driven hyperglycaemia.

Preclinical and clinical research highlights

Phase 2 obesity programmes. Published Phase 2 work has reported clinically meaningful body-weight reduction at 24-week and 48-week endpoints with subcutaneous mezdutide administration in adults with obesity, with dose-dependent reductions in body weight, waist circumference, and liver-fat content as assessed by MRI-PDFF.

Type 2 diabetes programmes. Phase 2 work in adults with type 2 diabetes has reported improvements in HbA1c, fasting glucose, and lipid parameters consistent with the broader incretin class.

Hepatic steatosis. Reductions in liver-fat content reported in mezdutide trials have generated interest in dual-agonist development for metabolic dysfunction–associated steatohepatitis (MASH) — a research direction also being pursued for survodutide and pemvidutide. Glucagon-receptor activation is the proposed primary contributor to the hepatic-fat reduction observed beyond what GLP-1 monotherapy typically delivers.

Adverse-event profile. As with the rest of the incretin class, gastrointestinal effects (nausea, vomiting, diarrhoea) dominate the adverse-event profile, generally dose-related and prominent during dose escalation. Glucagon-receptor activation introduces additional theoretical considerations around glycaemia and heart rate that are tracked in trial design.

Position within the incretin landscape

Mezdutide represents one approach within a competitive subclass: GLP-1/glucagon dual agonists are also represented by survodutide (Boehringer Ingelheim/Zealand) and pemvidutide (Altimmune), each with distinct receptor-affinity ratios and clinical-trial programmes. The broader class also includes the GLP-1/GIP dual agonist tirzepatide (Mounjaro/Zepbound, FDA-approved) and the GLP-1/GIP/glucagon triple agonist retatrutide (Phase 3). Comparative head-to-head data across these agents remains limited.

Current research status

Mezdutide is an investigational research peptide. It is not approved by the FDA. Late-stage Phase 3 development is concentrated in China through Innovent Biologics. As of the time of writing, mezdutide had not received approval in any jurisdiction; readers should verify current regulatory status against primary sources before relying on this summary.

Key takeaways for researchers

  • Mezdutide (mazdutide, IBI362) is an investigational GLP-1 / glucagon receptor dual agonist developed by Innovent Biologics.
  • It is positioned within the "twincretin" subclass alongside survodutide and pemvidutide, distinct from pure GLP-1 agonists and from GLP-1/GIP agents.
  • Reported Phase 2 endpoints include body-weight reduction, glycaemic improvement, and liver-fat reduction.
  • Late-stage development is concentrated in China; global regulatory status should be verified against primary sources.
  • Mezdutide is not an FDA-approved drug.

References

  1. Ji L, Jiang H, Bi Y, et al. Efficacy and safety of mazdutide, a dual GLP-1 and glucagon receptor agonist, in adults with obesity: clinical development overview. Cell Metabolism and journal-of-record publications from the IBI362 Phase 2 programme. (See Innovent Biologics development pipeline disclosures and primary trial publications for current data.)

This article is provided for educational and research purposes only. Mezdutide is an investigational research peptide and is not an FDA-approved drug. It is not intended for self-administration, and any research-context handling should be conducted by qualified personnel within an appropriate institutional setting and in compliance with applicable regulatory requirements. Nothing in this article constitutes medical advice or a recommendation for use.