Cagrilintide 10mg*10vials

▎Cagrilintide Structure

▎Cagrilintide Research

What is the research background of Cagrilintide?

Cagrilintide is a dual amylin and calcitonin receptor agonist (DACRA) developed based on the structure of amylin. Amylin is secreted by pancreatic islet β cells and works in concert with insulin to exert various physiological functions. It can induce a feeling of satiety and reduce food intake, mainly by activating the receptors in the area postrema at the base of the fourth ventricle. The neural signals are transmitted to the forebrain through the nucleus of the solitary tract and can also be transmitted to the lateral hypothalamic area and other nuclear groups via the lateral parabrachial nucleus, thereby exciting the satiety center and inhibiting food intake^[1]. Amylin can also regulate glucose homeostasis by inhibiting the secretion of insulin and glucagon to maintain stable blood glucose levels^[2]. Its mechanisms include a direct effect on pancreatic islet α cells and an indirect regulation of glucagon secretion through neural signals in the hypothalamus. In patients with diabetes, the destruction of β cells leads to a decrease in amylin secretion. Amylin participates in the regulation of glucose homeostasis by inhibiting gastric emptying and postprandial hepatic glucose production, reducing postprandial blood glucose fluctuations. It can also delay gastric emptying, inhibit gastrointestinal peristalsis, prolong the residence time of food, and prevent a sharp rise in blood glucose. However, the short half-life of natural amylin limits its clinical application. Although pramlintide is available as an adjuvant drug, it requires three injections a day, which is inconvenient and results in poor compliance ^[3]. To address this issue, Cagrilintide was developed. Its research and development are based on a deep understanding of the physiological functions of natural amylin, aiming to mimic its mechanism of action while improving the stability and long-acting properties of the drug to meet clinical needs.

What is Cagrilintide?

Cagrilintide is a novel long-acting amylin analog with great potential, having already shown initial effectiveness in the treatment of obesity and diabetes. It has been lipidated and possesses stable and long-acting characteristics ^[3]. Amylin is co-released with insulin by pancreatic β cells and induces a feeling of satiety by acting on the homeostatic and pleasure regions of the brain. As an analog, Cagrilintide can mimic this effect, inducing satiety to help control body weight. At the same time, as a dual amylin and calcitonin receptor agonist (DACRA), it is derived from the amylin backbone and has a unique mechanism in metabolic regulation.

Structural Model of Cagrinlintide

Source:PubMed^[3]

What are the related applications of Cagrilintide?

In clinical trials, Cagrilintide has achieved positive results in inducing weight loss. For example, in a multicenter, randomized, double-blind, placebo-controlled, and active comparator Phase 2 dose-finding trial, compared with the placebo group, the average percentage of weight loss from baseline in each dose group of Cagrilintide (0.3 - 4.5 mg) (6.0% - 10.8%) was higher than that in the placebo group (3.0%). The weight loss in the 4.5 mg group was also greater than that in the liraglutide 3.0 mg group (10.8% vs. 9.0%), indicating that it can be an effective option for weight management^[4]. Cagrilintide has a different but related mechanism of action compared with the GLP-1 receptor agonist semaglutide. Semaglutid reduces appetite, increases insulin secretion, and delays gastric emptying by acting on the GLP-1 receptors in the hypothalamus, while Cagrilintide further reduces appetite by activating the amylin receptor. The combined use of the two can produce a superimposed effect, significantly enhancing the weight loss effect^[5]. Given the complexity of obesity, this combined treatment is a reasonable and effective strategy.

In patients with type 2 diabetes, Cagrilintide has also demonstrated good blood glucose control ability. Clinical studies have shown that it has good stability and effectiveness in the treatment of obesity and type 2 diabetes. For example, in a clinical trial of patients with type 2 diabetes, the combined use of Cagrilintide and the GLP-1 receptor agonist semaglutide showed good blood glucose control and weight loss effects^[6]. Another trial also demonstrated its good tolerability and safety when used alone or in combination with semaglutide^[6], because the stability of the drug is closely related to its tolerability and safety.

In addition, Cagrilintide has been well tolerated in clinical trials. In the Phase 2 dose-finding trial, the permanent discontinuation rates in each treatment group were similar, mostly due to adverse events. However, the most common adverse events were gastrointestinal disorders and injection site reactions, and most of them were mild to moderate. In a randomized, controlled Phase 1b trial, the combined treatment of Cagrilintide and 2.4 mg semaglutide also showed good tolerability and safety ^[7]. Larger-scale and longer-term trials are needed in the future to comprehensively evaluate the effectiveness and safety of this combined treatment.

Cagrilintide brings new hope for the treatment of obesity and type 2 diabetes. It provides a new treatment option for obese patients, especially those who do not respond well to lifestyle interventions and are not suitable for bariatric surgery. Its unique mechanism of action provides new ideas and methods for the treatment of obesity, and it may have more advantages than traditional weight loss drugs (D'Ascanio A M, 2024). The successful case of the combined use of Cagrilintide and semaglutide (CagriSema) shows that multi-target combined treatment is an effective strategy to improve the treatment response for obesity^[6]. This model provides a new paradigm for the management of obesity and also brings significant metabolic improvements to patients with type 2 diabetes.

In conclusion, as a novel long-acting amylin analog, Cagrilintide has significant potential for weight loss and blood glucose control. It activates the satiety signaling pathway by mimicking the action of amylin and regulates metabolism as a dual receptor agonist. Clinical trials have shown that Cagrilintide, either alone or in combination with semaglutide, can significantly reduce body weight and is well tolerated. In addition, it has also shown good blood glucose control ability in patients with type 2 diabetes, providing a new treatment option for the treatment of obesity and diabetes, filling the gap in existing treatment regimens, especially for patients who do not respond well to lifestyle interventions and are not suitable for surgery. Its multi-target treatment strategy provides new ideas for the management of metabolic diseases.

About The Author

The above-mentioned materials are all researched, edited and compiled by Cocer Peptides.

Scientific Journal Author

Dr. D. C. W. Lau is a professor at the Cumming School of Medicine, University of Calgary, Canada. His research interests cover endocrinology and metabolism, general and internal medicine, cardiovascular system and cardiology, public health, environmental and occupational health, as well as oncology. He also holds positions with Alberta Health Services (AHS) and Obesity Canada and works at the Julia McFarlane Diabetes Research Centre. Dr. Lau has extensive experience in the fields of diabetes and obesity research, with his work published in academic journals such as the Canadian Journal of Diabetes. Dr. D. C. W. is listed in the reference of citation [4].

▎Relevant Citations

[1] Hansen K E, Murali S, Chaves I Z, et al. Glycomacropeptide Impacts Amylin-Mediated Satiety, Postprandial Markers of Glucose Homeostasis, and the Fecal Microbiome in Obese Postmenopausal Women[J]. Journal of Nutrition, 2023,153(7):1915-1929.DOI:10.1016/j.tjnut.2023.03.014.

[2] Ling W, Huang Y, Qiao Y, et al. Human Amylin: From Pathology to Physiology and Pharmacology[J]. Current Protein & Peptide Science, 2019,20(9):944-957.DOI:10.2174/1389203720666190328111833.

[3] Kruse T, Hansen J L, Dahl K, et al. Development of Cagrilintide, a Long-Acting Amylin Analogue[J]. Journal of Medicinal Chemistry, 2021,64(15):11183-11194.DOI:10.1021/acs.jmedchem.1c00565.

[4] Lau D C W, Erichsen L, Francisco A M, et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial[J]. Lancet, 2021,398(10317):2160-2172.DOI:10.1016/S0140-6736(21)01751-7.

[5] D'Ascanio A M, Mullally J A, Frishman W H. Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity[J]. Cardiology in Review, 2024,32(1):83-90.DOI:10.1097/CRD.0000000000000513.

[6] Frias J P, Deenadayalan S, Erichsen L, et al. Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial[J]. Lancet, 2023,402(10403):720-730.DOI:10.1016/S0140-6736(23)01163-7.

[7] Enebo L B, Berthelsen K K, Kankam M, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial[J]. Lancet, 2021,397(10286):1736-1748.DOI:10.1016/S0140-6736(21)00845-X.

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