Mazdutide

Mazdutide (LY3305677, IBI362) is a synthetic peptide that acts as a dual agonist of the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). It belongs to the family of oxyntomodulin analogues, modelled on the gut peptide oxyntomodulin, which naturally activates both of these receptors. The molecule has the formula C207H317N45O65 and a molar mass of about 4,476 g/mol, placing it among the structurally diverse single, dual and triple receptor agonist peptides built around the GLP-1 receptor.

Mazdutide in the research literature

In a diet-induced mouse model and in fatty-acid-loaded hepatocytes, mazdutide has been studied for its effects on hepatic lipid handling. That work reported modulation of the PERK branch of endoplasmic reticulum stress signaling, reduced NF-kB-mediated inflammatory signaling, and lower expression of lipogenic regulators including SREBP-1 and PPAR-gamma. A separate mouse study used ultrahigh-field 9.4-T MRI to quantify hepatic lipid and iron measures, comparing the dual agonist with a selective GLP-1R agonist and correlating imaging values with histology.

Analytically, mazdutide has been included in a validated multiplexed liquid chromatography high-resolution mass spectrometry method for identifying and quantifying structurally diverse GLP-1 receptor agonist peptides by accurate mass and fragmentation.