Mazdutide: A Dual GLP-1/Glucagon Receptor Peptide for In Vitro metabolic and Endocrine Research 

Mazdutide is a novel dual incretin receptor agonist (also known as an OXM analog) designed to simultaneously activate the glucagon-like peptide-1 receptor (GLP-1R) and glucagon receptor (GCGR). It is under investigation for its potent metabolic regulatory effects, including appetite suppression, glucose control, lipid metabolism, and body weight reduction.

Mazdutide is derived from oxyntomodulin (OXM), a 37-amino acid peptide hormone, and is chemically modified to improve half-life, stability, and bioactivity for research purposes.

Chemical Information

• CAS Number: 2259884-03-0
• Synonyms: IBI362, Oxyntomodulin analog
• Molecular Formula: C241H358N64O76
• Molecular Weight: ~5500 Da
• Sequence (modified analog of Oxyntomodulin):

H-His-Ser-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Gly-Gln-Ala-Ala-Lys-Glu-Phe-Ile-Ala-Trp-Leu-Val-Lys-Gly-Arg-Gly-Asp-Phe-Ile-Asn-Trp-Leu-Ile-Glu-Gln-Lys-NH

Peptide Modifications:

• N-terminal fatty acylation (e.g., C18 diacid chain) for albumin binding and extended half-life
• Strategic amino acid substitutions to enhance receptor selectivity and reduce proteolytic degradation
• C-terminal amidation to improve metabolic stability

Mechanism of Action

Mazdutide is a balanced dual agonist of the GLP-1 and glucagon receptors, mimicking the action of endogenous oxyntomodulin but with improved receptor activation and pharmacokinetics.

GLP-1R Activation:

• Enhances insulin secretion (glucose-dependent)
• Suppresses glucagon release
• Slows gastric emptying
• Reduces appetite via CNS signaling

GCGR Activation:

• Increases energy expenditure
• Promotes lipolysis
• May counteract hypoglycemia risk from insulinotropic action

The synergy between these receptor pathways contributes to enhanced metabolic effects beyond those of GLP-1 agonists alone.

Research Applications

Preclinical and early clinical research has demonstrated that Mazdutide exhibits:

• • Potent anti-obesity effects in diet-induced obese (DIO) mice and nonhuman primates
  • Improvements in insulin sensitivity and glycemic control
  • Reduction in hepatic steatosis and plasma lipids
  • No severe adverse hypoglycemia, owing to glucagon counter regulation

Selected Research and References

• Shi, Y. et al. (2023)  “Mazdutide, a GLP-1 and glucagon receptor dual agonist, for the treatment of obesity: a phase 1b trial.”  The Lancet Gastroenterology & Hepatology  https://doi.org/10.1016/S2468-1253(23)000161
• Henderson, S.J. et al. (2016) “Pharmacological actions of the glucagon-like peptide-1/glucagon receptor co-agonist oxyntomodulin in humans and rodents.” Diabetes Obes Metab. 2016;18(1):40–48  https://doi.org/10.1111/dom.12577
• Zhou, W. et al. (2022) “Preclinical and clinical evidence of Mazdutide (IBI362) as a dual GLP-1R/GCGR agonist for metabolic disorders.”  J Transl Med. 20, 587 (2022).  https://doi.org/10.1186/s12967-022-03835-2

Future Research Directions

Ongoing and future areas of exploration for Mazdutide include:

• Obesity and Type 2 Diabetes therapies with durable weight loss
• Non-alcoholic fatty liver disease (NAFLD) and NASH
• Cardiometabolic disorder mitigation
• Long-acting, once-weekly injectable therapies
• Exploring combinations with GIP receptor agonists or SGLT2 inhibitors

Due to its favorable dual-receptor profile and emerging clinical data, Mazdutide is considered a promising investigational tool for metabolic disease modeling and receptor biology.

Disclaimer

This product is intended for research purposes only. Thymalin is not approved for human or veterinary use, nor is it intended for clinical, diagnostic, or therapeutic applications. All research activities must comply with applicable local laws and institutional guidelines. Misuse of this compound for human consumption is strictly prohibited.