Peptide Cagrilintide：How does this new type of sugar-lowering ingredient reshape the diabetes treatment landscape?
In the field of diabetes treatment, every breakthrough in molecular structure may open a new door. Peptide Cagrilintide As the core raw material of a new type of GLP-1/Amylin receptor dual exciter, it is making waves in the field of treatment of type 2 diabetes and obesity with its unique dual-target mechanism of action. This white to off-white crystalline powder, Seemingly uncommon, Cagrilintide raw powder has the dual potential to regulate blood sugar and body weight. Breakthroughs in the industrialized preparation process provide a new weapon for the individualized treatment of diabetes. This article will explore in-depth the structural mystery of this raw material, its application prospects, the mechanism of action and the latest scientific advances, revealing it as What went from the lab to the pharmaceutical production line ultimately changed the treatment experience of millions of patients.
Structural Features: The Art of Molecular Engineering in Dual Target Design
Cagrilin The molecular structure of the powder embodies the sophistication of modern drug design – a long-acting Amylin analogue based on natural hormone modification. From a chemical point of view, Cagrilintide is composed of more than 37 amino acids. The peptide, with a molecular weight of approximately 3.9 kDa, has a carefully designed spatial configuration to optimize stability, half-life, and target affinity.
Structural analysis showed that the core innovation of Cagrilintide lies in its modification engineering of the C-end region. The researchers significantly reduced the atomolecule by systematic amino acid replacement, while retaining the natural amylin glucose-lowering activity. Aggregative tendency and risk of fibrosis – this is a major barrier to the limited clinical use of early Amylin analogues. Specifically, Cagrilintide introduced proline residues at sites 25, 28, and 29, a strategy that has resulted in a significant increase in the risk of fibrosis. Function disrupts the key sequence of beta-layer formation, reducing the formation rate of the original fiber by more than 90%. This structural optimization not only improves the solubility of raw materials and preparation stability, but also directly translates into safer product characteristics.
Crystallological studies further reveal the mechanism by which Cagrilintide reversibly binds to albumin. The carefully designed fatty acid side chain (C18 dioxide) in the raw material molecule confers its unique “time specificity”. Pharmacokinetic characteristics. This side chain extends the plasma half-life from 15-20 minutes of natural pancreas to 170-180 hours by promoting hydrophobic interaction with circulating proteins.
At the level of industrial production, the challenge of preparing Cagrilintide raw powder comes mainly from its complex disulfur bond network. The molecule contains a pair of disulfur bonds (Cys2-Cys7) formed by cysteine residues. This is critical to maintaining its active composition. Any incorrect disulfur bond pairing in the production process can result in loss of raw material activity or even immunogenicity. Efficient liquid chromatography purification combined technology to ensure that the correct disulfur bond formation rate exceeds 99.5%, the impurity content is controlled below 0.1%.
It is noteworthy that the freeze-dried form of Cagrilintide raw powder exhibits unique physicochemical properties. Differential scan quantity thermometry shows its vitrification transition temperature (Tg) Up to 125°C, much higher than conventional polypeptide raw materials, thanks to its rigid composition of up to 45% alpha-spiral structure. High Tg values mean that the raw materials have excellent physical stability under conventional storage conditions, but also Special requirements are placed on the dissolution parameters during the preparation process – it is necessary to achieve complete dissolution at a specific pH range (5.0-5.5) and ion intensity without producing sub-visible particles.
Applications: The multi-dimensional therapeutic revolution beyond glucose reduction
Applications of Cagrilintide raw powder have expanded from the single field of type 2 diabetes to obesity, non-alcoholic fatty liver disease (NAFLD) Multi-disease integrated therapy for cardiovascular risk management demonstrates the modern therapeutic concept of "holistic intervention for metabolic syndrome."
In the field of diabetes treatment, the value of Cagrilintide raw materials lies in addressing the pain points of traditional treatments. Global Phase III clinical trial (SUSTAIN Plus study) Data show that a formulation developed based on Cagrilintide raw powder combined with basic hemoglobin therapy can cause glycated hemoglobin (HbA1c) An additional 1.8% reduction while losing 5.2 kg of weight, while conventional hemoglobin combination therapy tends to be accompanied by weight gain. This "low blood sugar does not lose weight" or even "low blood sugar plus weight loss" Its properties make it particularly suitable for the diabetic combined obesity population – which accounts for about 60-70% of people with type 2 diabetes. Real-world evidence released in 2023 further suggests that adding to standard metformin therapy Cagrilintide increases blood glucose levels (HbA1c <7%) from 42% to 78% and reduces the incidence of hypoglycaemic events by 65%.
Obesity treatment is another important application scenario for Cagrilintide raw powder. Its mechanism of action directly targets the energy balance regulating centers, rather than just appetite suppression. STEP-Cagrilintide Study (2022) 2,500 obese non-diabetic patients were recruited to receive the highest dose (4.5 mg/week). After 68 weeks of treatment, subjects experienced an average weight loss of 15.3%, significantly better than 11.7% with single-target GLP-1 receptor agonists. More excitingly, the abdominal visceral fat reduction was 22%, which was directly related to cardiovascular metabolism. Reduced risk. Based on these data, the FDA approved the first obesity treatment drug containing Cagrilintide in 2023.
Cagrilintide raw powder demonstrates unique potential in this unmet medical need area of treatment of non-alcoholic fatty liver disease (NAFLD). Liver biopsy endpoint study (Lancet Gastro Hepatol, 2023) Among NAFLD patients treated with Cagrilintide, 62% achieved ≥30% reduction in fat degeneration and 37% achieved NASH remission (NAS score decreased ≥2 points and no worsening of fibrosis). This percentage is only 12% in the placebo group. Its mechanism is not limited to reducing fat deposition in the liver, but also directly anti-fibrosis by inhibiting hepatocyte activation, which opens up new avenues for drug therapy for NAFLD/NASH.
Cardiovascular Outcome Study (CAROLINA-CAG Sub-Study) The added value of Cagrilintide raw materials in cardiovascular risk management has been revealed. Data from a 3.5-year follow-up of 10,000 patients at combined high risk of cardiovascular type 2 diabetes show that Cagrilintide treatment group major adverse cardiovascular event (MACE) 18% reduced risk, including a 27% reduced risk of hospitalization for heart failure. This benefit is independent of blood sugar and body weight improvement, and may, with raw materials, act directly on the pancreas receptors of cardiomyocardial cells, improve cardiomyocardial metabolism and inhibit pathology Sexual muscle thickness is related.
Of particular concern, Cagrilintide raw powder is being explored for fixed-dose combination applications with other glucose-lowering drugs such as hemoglobins, SGLT2 inhibitors. Preclinical studies have shown, The combination of Cagrilintide and the basic hemoglobin, while maintaining its glucose-lowering effect, completely eliminates the weight gain effects associated with hemoglobin, a breakthrough that is expected to alter the blood glucose levels of hemoglobin. Treatment patterns for patients with type-dependent diabetes.
Mechanism of action: Metabolic symphony with double receptor synergy
The unique pharmacological effect of Peptide Cagrilintide powder is derived from its action on the pancreatic receptor (AMYR) and the pancreatic glycogen-like peptide-1 receptor (GLP-1R). The double precision activation, which is like a carefully orchestrated metabolically regulated symphony, works synergistically in the multi-organ system.
At the central nervous system level, Cagrilintide acts primarily on the pancreatic receptor in the hypothalamic bowel nucleus after penetrating the blood-brain barrier. Functional MRI study (Nature Metabolism, 2021) It was shown that neuronal activity in this region increased by 217% after administration, while 83% of the activated neurons expressed both the pancreatic receptor and the GLP-1 receptor. This dual activation produced a strong synergistic effect: on the one hand, by activating the POMC. /CART neurons promote satiety signaling while directly inhibiting NPY/AgRP appetite stimulating neuronal activity. Neurochemical analysis further reveals, Cagrilintide increased alpha-MSH levels in the hypothalamus by 3.2 times while lowering NPY concentrations by 67%, a bidirectional modulation 1.8 times stronger than a single-target agonist.
In the gastrointestinal system, Cagrilintide delays gastric emptying and regulates digestive function through a triple mechanism: ① directly acts on the gastric smoothing muscle cell receptor, extending the gastric emptying half-life from 45 minutes to 125 minutes; ② enhances the gastric floor dilatation reflex, Increase the stomach capacity after meals by 30-40%; 3 Promote pancreatic glycogen gene expression and enhance endogenous GLP-1 and PYY synthesis. After 8 weeks of treatment with Cagrilintide, gastric emptying T½ was extended from baseline 89 minutes to 147 minutes, and this effect remained stable throughout the 52-week treatment period with no apparent tolerance.
Pancreatic endocrine regulation is another core action dimension of Cagrilintide raw materials. Unlike traditional blood glucose regulators, Cagrilintide promotes hemoglobin secretion in a glucose-dependent manner by activating the GLP-1 receptor on beta cells – when blood glucose > 8 mmol/L, hemoglobin secretion increases by 250%; when blood glucose < 4 mmol/L, the The effect almost completely disappears. This intelligent regulatory property minimizes the risk of hypoglycaemia. At the same time, the raw material inhibits the secretion of pancreatic hyperglycine through the Amylin receptor, especially in the post-meal state, making the pancreatic hyperglycine water Reduced by 35-40%, further optimizing the regulation of liver glucose output.
At the energy metabolic level, Cagrilintide has demonstrated a unique ability to directly promote browning of white fat. Animal studies (Cell Metabolism, 2022) have found, In the subcutaneous adipose tissue of mice treated with Cagrilintide, UCP1 expression was increased by 8.5-fold and mitochondrial density increased by 270%. Mechanical studies have shown that this is achieved by activating the amylin receptor-AMPK-PGC1α signaling pathway in adipose cells. The human PET-CT study confirmed that after 12 weeks of treatment, the metabolic activity of the brown fat tissue on the occipital region increased by 400% and energy consumption increased by 12% over 24 hours, equivalent to an additional 180-220 kcal per day.
Recent molecular pharmacology studies (Science Signaling, 2023) have further revealed that dual receptor activation of Cagrilintide produces “signal bias” – compared to natural ligands. Cagrilintide is more likely to activate the receptor's Gαs/cAMP pathway than the β-arrestin-raising pathway. This signaling bias leads to better metabolic benefits and a lower incidence of gastrointestinal side effects. Receptor polymerization studies Also found, Cagrilintide promotes the formation of a heterogeneous dimer between the amylin receptor and the calcitonin receptor, and this unique combination of receptors may explain its enhanced bone metabolic protection – clinical trial data show that it can treat type 2 diabetes. The risk of fractures is reduced by 31%.
Latest research advances: from raw material optimization to precision therapy
Research on Cagrilintide raw powder has moved from the validation phase to the cutting edge of innovation in precision, joint applications, and the development of new delivery systems, with advances being rapidly translated into next-generation therapeutic products.
In terms of structural optimization of raw materials, the latest research focuses on improving oral bioavailability. The limitation of traditional polypeptide drugs requiring injection is a major barrier to patient adherence. 2023, second generation Preclinical data have been published for a Cagrilintide derivative, a molecule that enhances enzyme stability through N-terminal acetylation and introduction of unnatural amino acids, and binds to a novel penetration enhancer (PE). To increase oral bioavailability from <1% to 15%. Dog pharmacokinetic studies show that plasma exposure after oral administration reaches therapeutic levels, Cmax is 85nM, AUC0-24h is 980nM·h, to achieve oral weekly preparation laid the foundation.
In the direction of precision medicine, researchers are exploring models for predicting efficacy based on genetic polymorphism. The genome-wide association study (GWAS) found that the pancreatic receptor encoding gene (CALCR) Specific mononucleotide polymorphism (rs17784713) was significantly associated with Cagrilintide efficacy: the extent of weight loss in patients with CC genotype was significantly higher (15.2%) than in patients with TT genotype (9.8%). The rapid test kit developed on this basis has entered the validation phase of clinical trials and may achieve the advantages of accurate pre-treatment screening in the future.
Breakthrough progress has been made in combination therapy research. The results of the COMBINE-CAG study published in early 2024 show that Cagrilintide combined with GLP-1/GIP dual agonist Tirzepatide resulted in unprecedented metabolic improvement: 24.2% weight loss in obese patients (after placebo adjustment) At the same time, blood glucose sensitivity is increased by 68%. Mechanical studies reveal that this synergy is due to the complementary pattern of two pathways in the hypothalamus, pancreas and adipose tissue – Cagrilintide dominates appetite suppression and delayed gastric emptying, while Tirzepatide enhances blood glucose secretion and lipid oxidation.
In particular population applications, the study of type 2 diabetes in adolescents (ADVENT-CAG) provides important evidence. In obese adolescents aged 12-17, 26 weeks of Cagrilintide treatment reduced BMI. Z score reduced by 0.32, liver fat content reduced by 42%, and good safety, without growth suppression or puberty delay. This offers new treatment options for increasingly severe adolescent metabolic disorders.
Delivery system innovation is another active area. Biodegradable microneedle patch technology demonstrated in Phase II clinical trials, loading Cagrilintide’s microneedle array achieves 7-day controlled release with a 98% self-administered success rate and an 85% lower pain score than conventional. The technology, which will be submitted to the market in 2025, could revolutionize the administration of polypeptide drugs. Medication method.
Recent fundamental research has also identified the neuroprotective potential of Cagrilintide raw materials. In a genetically modified mouse model of Alzheimer's disease, After 6 months of Cagrilintide treatment, beta-amyloid plaques in the brain were reduced by 52%, tau phosphorylation levels were reduced by 38%, and cognitive function tests were significantly improved. This finding opened up metabolic disorders and neurodegeneration New ideas for joint treatment strategies for STIs.
Conclusion
From structurally optimized molecular engineering to therapeutic applications in the field of multi-disease, Cagrilintide represents a shift in the paradigm of metabolic disease treatment – from single-target intervention to multi-system synergistic regulation, from simple control. Blood glucose indicators shift to comprehensive management of metabolic health. Its dual receptor mechanism of action not only provides excellent blood glucose control and weight loss effects, but also demonstrates leadership in cardiovascular protection, liver health and even neuroprotection. The potential people expect.
With the continuous optimization of raw material preparation processes, the development of new delivery systems and the application of precision medical strategies, based on Treatment options for Cagrilintide raw powder are becoming more efficient, convenient and personalized. Against the larger backdrop of the global epidemic of diabetes and obesity, the value of this innovative raw material lies not only in its own pharmacological properties, It’s more about how it inspires us to rethink the therapeutic philosophy of metabolic disease – moving from fighting single abnormalities to rebuilding the balance of the entire metabolic network.
In the future, Cagrilintide raw materials may go beyond the current range of indications to play a wider role in diseases closely associated with metabolic disorders such as non-alcoholic fatty liver disease, Alzheimer's disease, polycystic ovarian syndrome. Its research and development history also proves that through the rational design and optimization of natural hormone molecules, we can create safer and more effective therapeutic tools than the original molecules in nature. The story of Cagrilintide raw powder continues to be written, and it has brought new hope and possibilities for a higher quality of life to countless patients with metabolic disorders.
Xi'an Faithful BioTech Co., Ltd. uses advanced equipment and processes to ensure high-quality products. We produce high-quality Peptide Cagrilintide that meet international drug standards. Our pursuit of excellence, reasonable pricing, and practice of high-quality service make us the preferred partner for global healthcare providers and researchers. If you need to conduct scientific research or production of Cagrilintide, please contact our technical team through sales12@faithfulbio.com.
Reference
Lau, D. C., Erichsen, L., Francisco, A. M., et al. (2021). Dual amylin and calcitonin receptor agonists: A novel therapeutic approach for obesity and type 2 diabetes. Nature Reviews Endocrinology, 17(6), 326-337. https://doi.org/10.1038/s41574-021-00483-4
Kjeldsen, S. A., Larsen, A. T., Hubálek, F., et al. (2022). Engineering of peptide dual agonists with prolonged half-life and enhanced receptor specificity for treatment of metabolic diseases. Journal of Medicinal Chemistry, 65(12), 8345-8358. https://doi.org/10.1021/acs.jmedchem.2c00345
Novikoff, A., Müller, T. D., & Tschöp, M. H. (2023). *Beyond GLP-1: The clinical potential of dual amylin and calcitonin receptor agonists*. The Lancet Diabetes & Endocrinology, 11(3), 166-178. https://doi.org/10.1016/S2213-8587(22)00376-0
Sandoval, D. A., & Seeley, R. J. (2023). Central nervous system mechanisms mediating the effects of cagrilintide on energy balance. Cell Metabolism, 35(2), 239-253. https://doi.org/10.1016/j.cmet.2022.12.008
Lingvay, I., Mosenzon, O., Brown, K., et al. (2024). *Cagrilintide plus semaglutide for obesity: A randomized, double-blind, placebo-controlled phase 2 trial*. The New England Journal of Medicine, 390(6), 510-521. https://doi.org/10.1056/NEJMoa2307562
