Mazdutide

Mazdutide (IBI-362; LY-3305677; OXM-3) is a long-acting synthetic analogue of the mammalian gut hormone oxyntomodulin. It functions as a dual agonist of the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR), representing a novel therapeutic approach that combines the complementary metabolic benefits of both receptor pathways. The peptide structure incorporates a fatty-acyl moiety that extends its in vivo half-life. Mazdutide was developed through a collaboration between Innovent Biologics and Eli Lilly and received approval in China in 2025 for the treatment of type 2 diabetes and obesity.

Mazdutide exerts its effects through simultaneous activation of two complementary receptor pathways. Activation of the GLP-1 receptor (GLP-1R) promotes glucose-dependent insulin secretion, suppresses glucagon secretion, delays gastric emptying, and reduces appetite through central nervous system pathways. Activation of the glucagon receptor (GCGR) increases energy expenditure, promotes hepatic fat breakdown, and enhances fatty acid β-oxidation. This dual agonism not only provides synergistic weight reduction effects but also directly improves hepatic fat metabolism. Mazdutide binds human GCGR (Ki = 17.7 nM) and GLP-1R (Ki = 28.6 nM), and stimulates insulin secretion from mouse pancreatic islets (EC₅₀ = 5.2 nM).

• Obesity and Weight Management: Investigated for significant and sustained weight reduction. In Phase 2 obesity trials, mazdutide (9 mg) demonstrated clinically meaningful weight loss in Chinese adults with moderate to severe obesity. Dose-dependent reductions in body weight have been consistently observed.
• Type 2 Diabetes Mellitus: Studied for glycemic control with substantial improvements in HbA1c. At week 24, mazdutide significantly reduced HbA1c versus placebo: −1.57% with 4 mg and −2.15% with 6 mg, versus −0.14% with placebo. The compound has demonstrated superior efficacy compared to dulaglutide in patients with type 2 diabetes.
• Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and NAFLD: Investigated for reducing hepatic fat content and improving liver fat metabolism through GCGR-mediated mechanisms.
• Cardiometabolic Outcomes: Evaluated for effects on coronary plaque progression in patients with coronary atherosclerosis and overweight or obesity.
• Obstructive Sleep Apnea: Investigated in Phase 3 clinical trials for patients with moderate-to-severe OSA and BMI ≥ 28 kg/m².

CAS Number: 2259884-03-0
PubChem CID: 167312357 (also reported as 497620638 for SID)
Molecular Formula: C₂₁₀H₃₂₂N₄₆O₆₇
Molecular Weight: 4,563.06 g/mol
Sequence: H-{Aib}-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Glu-Lys-Lys-Ala-Lys-{AEEA-AEEA-γGlu-Nonadecanoic acid}-Glu-Phe-Val-Glu-Trp-Leu-Leu-Glu-Gly-Gly-Pro-Ser-Ser-Gly-NH₂
Purity: ≥ 99%
Form: Lyophilized powder
Storage: Store at ≤ -20°C in a cool, dry place, protected from light and moisture
Solubility: Soluble in sterile water and DMSO; prepare working solutions per laboratory protocol