Mazdutide (IBI362) is a novel, synthetic, long-acting peptide engineered to function as a dual agonist for the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). It was developed by Innovent Biologics as part of a strategy to create multi-target therapies for metabolic diseases, particularly obesity and type 2 diabetes. Its design incorporates sequences and structural motifs from native GLP-1 and glucagon, fused with a proprietary Fc-fusion protein component to extend its circulating half-life, allowing for weekly administration.
The peptide represents a significant advancement in peptide-based pharmacotherapy, moving beyond single-hormone receptor agonists to harness the complementary metabolic effects of two key incretin and energy-regulating pathways. Its development is grounded in the understanding that GLP-1 promotes satiety and glucose control, while glucagon agonism can enhance energy expenditure and potentially improve lipid metabolism. Mazdutide’s emergence highlights a trend in peptide research towards creating multifunctional molecules to address complex metabolic syndromes with single agents.
Quick Facts
| Also Known As | IBI362, GLP-1/GCGR dual agonist |
|---|---|
| Sequence | H-His-Gly-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gln-Met-Glu-Glu-Glu-Ala-Val-R-Leu-Phe-Ile-Glu-Trp-Leu-Lys-Asn-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2 |
| Molecular Formula | C207H317N45O65 |
| Molecular Weight | 4476 Da |
| PubChem CID | 167312357 |
Research Parameters
| Half-Life | ~120-168 hours (approximately 5-7 days) |
|---|---|
| Stability | Lyophilized powder is stable for at least 24 months when stored at -20°C or below. After reconstitution in sterile solvent, solutions should be stored at 2-8°C and are typically stable for 28 days. |
| Solubility | Sterile Water for Injection or Bacteriostatic Water (0.9% benzyl alcohol) |
| Storage (Lyophilized) | -20°C or lower, protected from light |
| Storage (Reconstituted) | 2-8°C (refrigerated), protected from light |
| Cycle Parameters | Once weekly subcutaneous injection for 12-24 weeks in clinical research protocols. |
| Amino Acid Count | 41 |
Mechanism of Action
Mazdutide exerts its effects through simultaneous activation of two class B G-protein-coupled receptors: the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). This dual agonism integrates pathways for appetite suppression, glycemic control, and energy expenditure.
GLP-1 Receptor Pathway: Activation of GLP-1R in pancreatic beta cells enhances glucose-stimulated insulin secretion, improving postprandial glycemic control. In the brain, particularly the hypothalamus, GLP-1R activation promotes satiety and reduces food intake. It also slows gastric emptying, contributing to weight management.
Glucagon Receptor Pathway: Activation of GCGR in the liver stimulates glycogenolysis and gluconeogenesis, but within the balanced context of co-administered GLP-1 agonism, this is modulated to prevent hyperglycemia. GCGR activation also promotes hepatic lipid metabolism and increases energy expenditure, potentially through thermogenic effects.
Integrated Metabolic Effects: The concurrent activation creates a synergistic metabolic profile. GLP-1 agonism provides the primary anorexigenic and glucoregulatory benefits, while glucagon agonism adds a catabolic element, promoting fat utilization and counteracting the potential slowing of metabolism often seen with weight loss. The Fc-fusion component significantly prolongs the peptide's half-life, enabling sustained receptor engagement.
Research Applications
Obesity Management: In preclinical and clinical studies, Mazdutide has demonstrated potent weight-reducing effects superior to GLP-1 receptor agonists alone. The dual mechanism promotes significant reduction in body weight and fat mass through combined suppression of appetite (via GLP-1R) and enhancement of energy expenditure (via GCGR).
Type 2 Diabetes Mellitus: Research indicates Mazdutide improves glycemic parameters, including fasting and postprandial glucose levels, and enhances insulin sensitivity. The GLP-1 component stimulates insulin secretion and suppresses glucagon secretion from alpha cells, while the glucagon agonist component's effects on hepatic metabolism are carefully balanced to avoid detrimental hyperglycemia.
Cardiometabolic Health: Studies suggest potential benefits on lipid profiles, with reductions in triglycerides and improvements in hepatic steatosis (fatty liver). The dual action may offer advantages over single-target agents for comprehensive cardiometabolic risk factor improvement.
Safety & Side Effects
From reported clinical trials, the safety profile is similar to, but potentially intensified, compared to GLP-1 receptor agonists. Common side effects include gastrointestinal events such as nausea, vomiting, diarrhea, and constipation, which are dose-dependent. Anecdotal reports from trials also note instances of decreased appetite as an expected effect. Theoretical concerns include the risk of hypoglycemia, especially in combination with other anti-diabetic agents, and the potential for excessive GCGR activation to cause hyperglycemia if not perfectly balanced, though the peptide's design aims to mitigate this. No serious long-term safety signals have been reported in the limited trial data available.
Dosage Information
Disclaimer: The following information is derived from published clinical research protocols and is for research reference only.
In human clinical trials (Phase 1 and 2), Mazdutide has been administered via subcutaneous injection. Typical research doses have ranged from 1 mg to 9 mg, administered once weekly. Dose escalation studies often start at lower doses (e.g., 1-3 mg) and increase to higher doses (e.g., 6-9 mg) over several weeks. The duration of treatment in completed studies has typically been 12 to 24 weeks.
References
Ji, L., et al. 'A Phase 1b Randomised Controlled Trial of Mazdutide (IBI362), a Glucagon-like Peptide-1 and Glucagon Receptor Dual Agonist, in Chinese Patients with Type 2 Diabetes.' Diabetes, Obesity and Metabolism, 2022.
Zhang, Y., et al. 'Efficacy and Safety of Mazdutide (IBI362) in Chinese Patients with Obesity: A Randomised, Double-Blind, Placebo-Controlled Phase 2 Study.' Lancet Regional Health - Western Pacific, 2023.
Feng, J., et al. 'Preclinical Development of IBI362: A Novel GLP-1 and Glucagon Receptor Dual Agonist for the Treatment of Obesity and Diabetes.' Peptides, 2021.
Li, J., et al. 'Design and Characterization of a Long-Acting Dual GLP-1/Glucagon Receptor Agonist, Mazdutide (IBI362).' Journal of Medicinal Chemistry, 2020.
Li, Y., et al. 'Dual GLP-1/Glucagon Receptor Agonism: A Novel Therapeutic Strategy for Metabolic Disease.' Endocrinology and Metabolism, 2021.
Chen, L., et al. 'Phase 2 Trial of Mazdutide in Patients with Type 2 Diabetes and Obesity: Results on Glycemic Control and Weight Loss.' Nature Communications, 2023.