Mazdutide (also known as IBI362 or LY3305677) is a synthetic peptide derivative of oxyntomodulin, functioning as a dual agonist for both the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). This dual activation is designed to synergistically enhance metabolic processes, offering potential therapeutic benefits in:​diabetesjournals.org+7pmc.ncbi.nlm.nih.gov+7en.wikipedia.org+7

• Weight Management: Mazdutide has demonstrated significant efficacy in reducing body weight among individuals with overweight or obesity. In a Phase 1b clinical trial involving Chinese adults with overweight or obesity, participants receiving mazdutide at doses up to 6 mg experienced a mean body weight loss of up to 6.4% over a 12-week period.  Subsequent studies with higher doses have shown even greater weight loss outcomes. ​en.wikipedia.org+8prnewswire.com+8pharmaceutical-technology.com+8pharmaceutical-technology.com+6pmc.ncbi.nlm.nih.gov+6nature.com+6
• Glycemic Control: By activating GLP-1R, mazdutide enhances insulin secretion and improves blood glucose regulation. Clinical studies have reported significant reductions in HbA1c levels, indicating improved glycemic control in patients with type 2 diabetes. ​pmc.ncbi.nlm.nih.gov+4biospace.com+4prnewswire.com+4
• Cardiometabolic Health: Beyond weight loss and glucose lowering, mazdutide has been associated with improvements in various cardiometabolic parameters, including reductions in waist circumference, blood lipids, blood pressure, and liver fat content. ​biospace.com+2prnewswire.com+2biospace.com+2

Research Highlights

• Phase 3 Clinical Trials: The GLORY-1 study, a Phase 3 clinical trial involving Chinese adults with overweight or obesity, demonstrated that mazdutide not only induced robust weight loss but also reduced liver fat content and improved multiple cardiometabolic risk factors. The study met its primary and all key secondary endpoints, supporting the potential of mazdutide as an effective treatment for obesity and related metabolic disorders. ​diabetesjournals.org+7prnewswire.com+7biospace.com+7prnewswire.com+3biospace.com+3biospace.com+3
• Regulatory Progress: Following the positive outcomes of the GLORY-1 study, Innovent Biologics submitted a New Drug Application (NDA) for mazdutide for chronic weight management, which has been accepted by the National Medical Products Administration (NMPA) of China. This marks a significant step toward making mazdutide available for clinical use in managing obesity. ​biospace.com+3biospace.com+3prnewswire.com+3

Structure

• IUPAC Name: 20-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(5S)-5-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-5-amino-2-[[2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]-2-methylpropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-4-carboxybutanoyl]amino]hexanoyl]amino]hexanoyl]amino]propanoyl]amino]-6-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[2-[(2S)-2-[[(2S)-1-[(2-amino-2-oxoethyl)amino]-3-hydroxy-1-oxopropan-2-yl]carbamoyl]pyrrolidin-1-yl]-2-oxoethyl]amino]-2-oxoethyl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-6-oxohexyl]amino]-2-oxoethoxy]ethoxy]ethylamino]-2-oxoethoxy]ethoxy]ethylamino]-1-carboxy-4-oxobutyl]amino]-20-oxoicosanoic acid​en.wikipedia.org
• Molecular Formula: C₂₀₇H₃₁₇N₄₅O₆₅​
• Molecular Weight: Approximately 4,500 Da​

Mazdutide represents a promising therapeutic option for managing obesity and type 2 diabetes, offering comprehensive benefits across multiple metabolic parameters. Ongoing and future studies will further elucidate its long-term efficacy and safety profile.​nature.com+3pharmaceutical-technology.com+3biospace.com+3

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​Mazdutide is a synthetic peptide that functions as a dual agonist for both the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). This dual activation is designed to enhance energy expenditure and improve glucose metabolism, offering potential therapeutic benefits for conditions such as obesity and type 2 diabetes.​medchemexpress.com+5biospace.com+5caltagmedsystems.co.uk+5

Research and Clinical Trials

• Weight Loss and Glycemic Control: In a Phase 3 clinical trial involving Chinese adults with type 2 diabetes, mazdutide demonstrated significant reductions in glycated hemoglobin (HbA1c) levels and body weight over a 24-week period. Specifically, participants receiving mazdutide experienced HbA1c reductions of 1.57% and 2.15% for the 4 mg and 6 mg doses, respectively, compared to a 0.14% reduction in the placebo group.Additionally, mazdutide treatment resulted in greater weight loss compared to placebo. ​biospace.com+1clinicaltrialsarena.com+1clinicaltrialsarena.com
• Cardiometabolic Benefits: Beyond glycemic control and weight loss, mazdutide has been associated with improvements in various cardiometabolic indicators, including reductions in waist circumference, blood lipids, blood pressure, blood uric acid, liver enzymes, liver fat content, and enhanced insulin sensitivity. ​clinicaltrialsarena.com+3prnewswire.com+3biospace.com+3
• Safety Profile: Clinical studies have reported that mazdutide is generally well-tolerated, with the most common adverse events being gastrointestinal in nature, typically mild to moderate in severity. ​clinicaltrialsarena.com

Structure

• Molecular Formula: C₂₁₀H₃₂₂N₄₆O₆₇​chemsrc.com
• Molecular Weight: Approximately 4,563.1 g/mol​
• Sequence: His-{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​clinisciences.com+1medchemexpress.com+1

The peptide includes a non-coded amino acid residue, alpha-amino isobutyric acid (Aib), at position 2, and is conjugated to a C20 fatty diacid moiety through a hydrophilic linker at the lysine residue at position 20. This modification enhances its binding to albumin in plasma, thereby prolonging its half-life. ​caltagmedsystems.co.uk

Conclusion

Mazdutide represents a promising therapeutic candidate for the management of obesity and type 2 diabetes, owing to its dual agonist activity on GLP-1R and GCGR. Clinical trials have demonstrated its efficacy in promoting weight loss, improving glycemic control, and offering additional cardiometabolic benefits, with a favorable safety profile. Ongoing research and further clinical evaluations will help to fully elucidate its therapeutic potential and long-term safety.