Cagrillntide

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.

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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