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ClinicalDual GLP-1/glucagon agonist for metabolic health

Mazdutide

Also indexed as IBI362, OXM3, Oxyntomodulin Analog 3

Mazdutide is a dual GLP-1/glucagon receptor co-agonist peptide developed by Innovent Biologics, originally derived from oxyntomodulin. It simultaneously activates both GLP-1 and glucagon receptors to produce robust reductions in body weight, blood glucose, and hepatic fat. Clinical trials in China have demonstrated significant efficacy for obesity and type 2 diabetes management.

Overview

Following subcutaneous injection, Mazdutide's fatty acid side chain mediates reversible albumin binding, extending plasma half-life to approximately 7 days and supporting once-weekly dosing. Peak plasma concentrations (Tmax) occur at approximately 24–72 hours post-injection. The compound distributes to GLP-1R-expressing tissues including pancreas, gut, brain (area postrema, hypothalamus), and GCGR-expressing tissues including liver and adipose tissue. Hepatic GCGR activation reduces steatosis via enhanced β-oxidation and reduced de novo lipogenesis, supported by preliminary biomarker and imaging data from Phase 2 trials. Renal clearance and proteolytic degradation are the primary elimination pathways.

Proposed mechanism

Mazdutide binds and activates both the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR) with balanced agonism. GLP-1R activation enhances glucose-dependent insulin secretion, reduces glucagon release, slows gastric emptying, and suppresses appetite via central hypothalamic pathways. Concurrent GCGR activation increases energy expenditure through thermogenesis, hepatic fatty acid oxidation, and lipolysis, amplifying weight loss and metabolic benefits beyond GLP-1 mono-agonism alone.

What the evidence supports

Randomised controlled trial data in humans exists and supports use in specific contexts.

Graded Clinical

Findings supported by randomised, controlled trials in humans, with pre-registered endpoints and published results.

Key citations

Representative primary sources, including results that did not favour the compound.

  1. [1]

    Once-weekly IBI362 (mazdutide) in Chinese adults with overweight or obesity: a multicentre, randomised, double-blind, placebo-controlled, multiple-dose, phase 2 trial

    · The Lancet Diabetes & Endocrinology, DOI: 10.1016/S2213-8587(23)00191-4 · 2023

  2. [2]

    IBI362 Phase 2 trial in type 2 diabetes mellitus — ClinicalTrials.gov registry

    · ClinicalTrials.gov Identifier: NCT04432844 · 2022

  3. [3]

    Dual GLP-1/glucagon receptor agonism for metabolic disease: mechanistic rationale and clinical development landscape

    · Nature Reviews Drug Discovery (review article) · 2022

  4. [4]

    Oxyntomodulin and related peptides as metabolic regulators: from physiology to pharmacology

    · Diabetes, Obesity and Metabolism · 2021

Citation records in this build are illustrative placeholders for the design.

Reference information for research purposes. Not medical advice, and not a recommendation to use any compound. Many entries describe substances that are not approved for human use.

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