For this order of retatrutide and cagrilintide from a long-standing German client, we utilized our proven shipping solution to Poland, ensuring a fully standardized, digitized, traceable, and coordinated process from order placement and payment through logistics to delivery confirmation. Upon receipt of payment, we activated our logistics plan, ensuring the safe transit of the goods via combined land-and-air transport between China and Europe, supported by real-time temperature monitoring. The system pushed tracking updates throughout the entire journey, allowing the client to view key information-such as customs clearance and transshipment status-at any time. Thanks to route optimization, the goods were delivered to Poland in just 9 days from the point of departure in China, with the outer packaging intact. The client expressed high satisfaction with our response speed, transparency, and professionalism. This successful delivery has strengthened the mutual trust between both parties and provided valuable experience for future optimizations of the European supply chain. We will continue to enhance the resilience of our services.
business Process
Cagrilintide is a long-acting analog of pancreatic amylin. Its uniqueness lies in its ability to act on both pancreatic amylin receptors and calcitonin receptors, making it a dual receptor agonist drug. Pancreatic amylin is a hormone secreted by pancreatic β cells along with insulin. It is released into the bloodstream after meals and its main physiological functions include inhibiting food intake, delaying gastric emptying, and suppressing post-meal glucagon secretion. Cagrilintide mimics the effects of natural pancreatic amylin and, through structural optimization, overcomes the defect of natural pancreatic amylin's tendency to form amyloid fibers, achieving a longer duration of action and better stability.
From the perspective of molecular mechanisms, the pancreatic amylin receptor is a heterodimer composed of the calcitonin receptor and a receptor activity-modifying protein.
Depending on the different RAMP subtypes, it can be classified into three subtypes: AMY1R, AMY2R, and AMY3R. After Cagrilintide binds to these receptors, it can activate the Gs protein signaling pathway, thereby regulating the downstream physiological effects.
The cryo-electron microscopy structure study reveals that when Cagrilintide binds to the receptor, it adopts a unique "circumferential" binding mode.
The 23rd phenylalanine residue anchors the peptide segment at the critical position on the receptor transmembrane bundle and the cell membrane interface.
The intramolecular salt bridge formed by the 14th glutamic acid and the 17th arginine effectively enhances the stability of the N-terminal α-helix of the peptide segment.
These structural features collectively constitute the molecular basis for the high affinity binding and efficient activation of the receptor by Cagrilintide.
Weight loss effect and clinical research
The weight loss efficacy of Cagrilintide has been verified in multiple clinical studies. In the REDEFINE 1 Phase 3 clinical trial, once-weekly subcutaneous injection of Cagrilintide at a dose of 2.4 mg combined with lifestyle intervention demonstrated clinically significant weight loss effects for adult patients with obesity or overweight and without diabetes.In the intention-to-treat analysis, after 68 weeks, the average weight loss in the Cagrilintide group was 11.5%, while that in the placebo group was 3.0%; it is notable that approximately 31% of the participants in the treatment group achieved a weight reduction of ≥15%, while the proportion in the placebo group was only 5.2%. These data represent the first 3-phase clinical trial evidence for the monotherapy of long-acting pancreatic amylin analogues for obesity, marking an important advancement in this target drug.
The weight loss effect of Cagrilintide is mainly mediated by the central nervous system. Animal studies have shown that Cagrilintide can activate the neuronal activities in brain regions such as the posterior brainstem, solitary nucleus, and lateral parabrachial nucleus, which are the key centers regulating feeding behavior and energy balance. It has been found that the weight loss effect of Cagrilintide is highly dependent on the two receptor subtypes, AMY1R and AMY3R. When the RAMP1 and RAMP3 genes of mice are knocked out, the weight loss efficacy of Cagrilintide is significantly weakened. Moreover, Cagrilintide mainly achieves weight reduction by reducing fat mass, while also helping to maintain relative lean body mass, which is of positive significance for the long-term metabolic health of obese patients.
The potential of combined therapy
The combined use of Cagrilintide and GLP-1 receptor agonists is currently a highly regarded treatment strategy. CagriSema, as a fixed-dose combination of Cagrilintide and semaglutide, has demonstrated remarkable efficacy in multiple clinical trials. In the REIMAGINE 2 3rd phase trial, for adult patients with type 2 diabetes, after 68 weeks of treatment with 2.4 mg/2.4 mg of CagriSema, a 1.91 percentage point reduction in HbA1c and a 14.2% weight reduction were achieved. Both indicators were superior to those of the respective single-component treatment groups. Additionally, in terms of weight reduction, 43% of the patients achieved a ≥15% weight reduction, and 24% achieved a ≥20% weight reduction. Moreover, the weight loss did not reach a plateau by the 68th week.
The network meta-analysis further supported the superiority of CagriSema. In the studies comparing CagriSema, Cagrilintide monotherapy, and semaglutide monotherapy, CagriSema ranked first in multiple indicators such as absolute weight loss, percentage weight reduction, HbA1c reduction, fasting blood glucose, systolic blood pressure, and waist circumference.
At the same time, CagriSema demonstrated good gastrointestinal tolerance, ranking best in terms of adverse events such as nausea, vomiting, and diarrhea. This balance between efficacy and tolerance may stem from the fact that the two drugs exert their weight loss effects through different but complementary pathways.
That is, the GLP-1 receptor agonist mainly acts on the hypothalamus and other pre-brain regions, while Cagrilintide acts more on the posterior brain regions. The combination of the two achieved a synergistic effect of "1 + 1 > 2".
Safety and tolerability characteristics
In terms of safety, Cagrilintide demonstrated good tolerance. The most common adverse events reported in the clinical trials were gastrointestinal reactions, including nausea, vomiting, diarrhea, and constipation. These reactions were mostly temporary, mild to moderate, and gradually subsided with the prolongation of treatment. In the REDEFINE 1 trial, the proportion of patients who permanently discontinued treatment due to nausea was 1.0% in the Cagrilintide group and 0.1% in the placebo group. It is noteworthy that compared with GLP-1 drugs, the incidence of vomiting with Cagrilintide was lower.
Additionally, Cagrilintide performed well in terms of serious adverse events and allergic reactions, and its safety was consistent with that of treatments based on incretin and amylin. It is worth noting that Novo Nordisk has initiated a clinical trial specifically targeting obese patients who previously discontinued GLP-1 receptor agonists due to gastrointestinal adverse events. The aim is to assess the tolerance of Cagrilintide in this specific population. This indicates that Cagrilintide may provide an alternative treatment option for patients who cannot tolerate the existing GLP-1 drugs, reflecting the development direction of individualized treatment.
Future Outlook
Cagrilintide, as a new generation of therapeutic drug based on the pancreatic amylin pathway, represents the diversified development in the field of obesity and metabolic disease treatment.
With the launch of the specialized Phase 3 RENEW program, the efficacy and safety of Cagrilintide in obese or overweight populations will be evaluated more comprehensively.
Meanwhile, the development of the CagriSema combination formulation in the two indications of obesity and type 2 diabetes is continuing, and it is expected to become the first combined treatment regimen based on pancreatic amylin.
From the perspective of basic research, there are still many areas that warrant in-depth exploration regarding the molecular mechanism of action of Cagrilintide, the differences in pharmacological effects across species, and its specific target sites in the central and peripheral tissues.
For instance, recent studies have revealed that Cagrilintide may have a diabetes-specific cyclic adenosine monophosphate signal regulation effect in the kidneys, suggesting that it may have multiple system benefits beyond weight loss.
With a deeper understanding of the pancreatic amylin signaling pathway, future development of more precise and efficient next-generation receptor-targeted drugs may lead to more options for individualized treatment of obesity and related metabolic diseases.
