CEDAR

Scientific Reference

Mazdutide (IBI362 / LY3305677)

Evidence profile: Human Phase 3 evidence

Mazdutide (IBI362 / LY3305677) is a dual glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist, and a synthetic analog of oxyntomodulin. Unlike GLP-1-only or GIP/GLP-1 therapies, it uniquely combines appetite suppression with increased energy expenditure via glucagon receptor activation. Clinical trials (GLORY-1, GLORY-2) demonstrate substantial weight loss outcomes of up to ~20% over 60 weeks, alongside improvements in glycemic control, lipid profiles, and liver fat reduction. This dual mechanism positions mazdutide as a next-generation metabolic therapy with both intake-reducing and expenditure-increasing effects.

Mechanism of Action

Mazdutide acts as a dual agonist at GLP-1 and glucagon receptors. GLP-1 activation enhances insulin secretion, suppresses glucagon, slows gastric emptying, and reduces appetite via central pathways. Glucagon receptor activation increases thermogenesis, energy expenditure, and hepatic fat metabolism. The GLP-1 component counterbalances glucagon-induced hyperglycemia, enabling a synergistic metabolic effect that promotes significant weight loss.

Molecular Information

  • Type: Dual GLP-1/Glucagon receptor agonist (oxyntomodulin analog)
  • Length: 33 amino acids
  • Molecular weight: 4476 g/mol
  • Molecular formula: C207H317N45O65
  • CAS: 2259884-03-0

Published Research

  • GLORY-2 (NCT06164873)

    Treatment With 9-mg Mazdutide for Weight Reduction in Chinese Adults With Obesity: The GLORY-2 Randomized Clinical Trial

    Gao L et al. · JAMA · 2026 · Clinical

    PMID 42251595 — View on PubMed

  • Mazdutide versus dulaglutide in Chinese adults with type 2 diabetes

    Guo L et al. · Nature · 2026 · Clinical

    PMID 41407860 — View on PubMed

  • Mazdutide versus placebo in Chinese adults with type 2 diabetes

    Zhu D et al. · Nature · 2026 · Clinical

    PMID 41407859 — View on PubMed

  • GLORY-1 (NCT05607680)

    Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight

    Ji L et al. · The New England journal of medicine · 2025 · Clinical

    PMID 40421736 — View on PubMed

  • NCT05623839

    Mazdutide reduces body weight in adults with overweight or obesity: A high-dose Phase 1 trial

    Bhattachar SN et al. · Diabetes, obesity & metabolism · 2025 · Clinical

    PMID 40832785 — View on PubMed

  • Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial

    Zhang B et al. · Diabetes care · 2024 · Clinical

    PMID 37943529 — View on PubMed