Cagrilintide – Amylin Analogue for Research on Obesity, Metabolism, and Glycemic Control
Cagrilintide is a long-acting synthetic analogue of amylin, a natural peptide secreted by pancreatic beta cells together with insulin. It is being studied for its potential in the experimental treatment of obesity, type 2 diabetes, and other metabolic disorders. Thanks to its resistance to enzymatic degradation, it has an extended half-life that provides more stable and long-lasting effects compared to natural amylin.
In animal models, Cagrilintide has shown a significant reduction in appetite, improved glycemic control, and sustained weight loss. It has been investigated not only for its effects on carbohydrate metabolism but also for its potential impact on liver injury, cardiovascular health, and neuronal protection. Some studies have observed a synergistic effect when combined with Semaglutide, with superior results in body weight reduction and body composition improvement.
Origin and Function of Amylin
Amylin (also known as IAPP – Islet Amyloid Polypeptide) is a peptide co-secreted with insulin by pancreatic beta cells. It acts as a regulator of energy metabolism by inducing satiety, slowing gastric emptying, and contributing to the stabilization of postprandial glucose levels. This regulatory mechanism helps prevent sharp fluctuations in blood glucose, promoting a more efficient use of sugars as an energy source and reducing their conversion into fat.
Amylin also plays a role in bone metabolism, sharing structural and functional similarities with calcitonin and the calcitonin gene-related peptide (CGRP). These peptides help reduce calcium levels in the blood by promoting its deposition in bones. However, endogenous amylin is rapidly degraded by the same enzymes that inactivate insulin, limiting its therapeutic effectiveness. Cagrilintide was designed to overcome this limitation, offering greater plasma stability and a prolonged duration of action.
Mechanism of Action of Cagrilintide
Cagrilintide acts through several physiological mechanisms involving the gastrointestinal tract, the central nervous system, and the pancreas. In the stomach, it slows food transit, prolonging digestion and promoting a sense of fullness. This process reduces overall caloric intake and limits postprandial glucose spikes. Additionally, its action on the central nervous system – particularly on the arcuate nucleus of the hypothalamus – stimulates satiety signals and modulates feeding behavior.
In the pancreas, Cagrilintide helps reduce glucagon secretion, a hormone that stimulates glucose production by the liver. This synergistic mechanism, similar to that observed with GLP-1 agonists, improves the balance between insulin and glucagon, reducing the body’s tendency to convert glucose into fat. The result is an improvement in the glycemic profile and a gradual reduction in fat mass.
Structure and Peptide Design
Cagrilintide represents an advanced example of peptide engineering. Its sequence has been modified to resist enzymatic degradation and to prevent the protein aggregation typical of natural amylin. The addition of proline residues in the terminal region reduces amyloid fibril formation, while the presence of a lipid chain at the N-terminal end enhances brain penetration and binding to amylin receptors (RAMP-1 and RAMP-3). These modifications give the peptide a prolonged half-life and a more favorable pharmacodynamic profile compared to its predecessors, such as pramlintide.
Research on Obesity and Metabolism
In experimental studies, weekly administration of Cagrilintide produced a 6–11% reduction in body weight within a few weeks compared to placebo. When combined with Semaglutide, the results were even more remarkable, with reductions of up to 17% of total body mass. This synergistic effect suggests a functional interaction between amylin and GLP-1 receptors, leading to a more effective suppression of appetite and improved insulin sensitivity.
Beyond its effects on weight loss, research has shown improvements in metabolic parameters such as fasting glucose, insulin levels, and glycated hemoglobin (HbA1c). These findings make Cagrilintide a promising candidate for metabolic and nutraceutical research, especially for studies on energy regulation and carbohydrate metabolism.
Cagrilintide and Cognitive Health
Interest in Cagrilintide extends beyond metabolism. Natural amylin has been associated with brain functions related to memory and cognitive regulation. Some studies have suggested a link between abnormal amylin levels and the formation of amyloid plaques in the brain, similar to those observed in Alzheimer’s disease. Although there is no conclusive data on the direct role of Cagrilintide in this area, its resistance to aggregation could theoretically contribute to neuroprotection and a reduction in oxidative stress in brain tissue.
The relationship between glycemic control and cognitive function is a growing focus in scientific research. Chronic hyperglycemia is known to increase inflammatory and oxidative processes that damage neuronal cells. By improving blood sugar regulation and insulin response, Cagrilintide could indirectly support better brain health and long-term cognitive function.
Synthesis and Research Applications
Cagrilintide is produced via solid-phase peptide synthesis (SPPS), ensuring high purity and stability. It is supplied as a lyophilized powder for research use only and can be reconstituted in aqueous solution or diluted acetic acid. Stable for up to 24 months at −20°C, it is suitable for long-term laboratory studies. Its use is restricted to scientific and cosmetic research contexts aimed at exploring metabolic regulation, hormonal signaling, and peptide interactions in weight and appetite control.
Note: The information provided is intended solely for descriptive and research purposes. Cagrilintide is not intended for human or veterinary use and must not be applied for therapeutic purposes. All handling should take place exclusively in controlled laboratory environments compliant with research regulations.
Scientific References
- PubChem – Cagrilintide
- Journal of Cellular Biochemistry
- Nature
- Appetite Journal
- Journal of Medicinal Chemistry
- Annual Review of Pharmacology and Toxicology
- Journal of Obesity & Metabolic Syndrome
- The Lancet
- The Lancet
- The Lancet – Recent Studies
- Diabetes, Obesity and Metabolism
- UCSF Research on Blood Sugar and Cognition
- PLoS One – Amylin and Cognitive Function





