Cagrilintide 5mg

Cagrilintide is a long-acting amylin analog currently under investigation for its potential in treating obesity and type 2 diabetes. It functions by mimicking the natural hormone amylin, which regulates blood sugar levels, appetite, and satiety. Cagrilintide has shown promise in clinical trials, demonstrating significant weight loss and improved glycemic control when administered alone or in combination with other agents like semaglutide.

Cagrilintide Research

Cagrilintide Origin: What Is Amylin?

Amylin (also known as islet amyloid polypeptide or IAPP) is a naturally occurring peptide released alongside insulin from pancreatic beta cells. Research indicates that amylin functions as an important signaling molecule in the brain, producing feelings of satiety. It is initially released as an 89–amino acid propeptide in approximately a 100:1 ratio relative to insulin. Similar to insulin, amylin is processed into a smaller active molecule consisting of 37 amino acids.

Amylin exerts multiple effects, including slowing gastric emptying, promoting satiety signals in the brain, and preventing glucose spikes after eating. Essentially, amylin moderates the rise in blood sugar post-meal, helping the body to better utilize sugar as an energy source instead of converting it to fat.

Amylin also influences bone metabolism, sharing structural and functional similarities with calcitonin and calcitonin gene-related peptide (CGRP). These peptides collectively reduce blood calcium levels by promoting calcium uptake into bones. Amylin may also affect calcium loss through the kidneys, although the significance of this is unclear. Overall, amylin contributes to increased bone deposition or protection against bone degradation.

In animal studies where the amylin gene is silenced, reduced appetite and lower caloric intake are observed. Amylin is degraded by the same enzymes responsible for insulin breakdown. However, cagrilintide is designed to resist these enzymes, granting it a longer half-life and thus more potent and sustained effects.

While still theoretical, amylin has been linked to amyloid-beta plaques characteristic of Alzheimer’s disease. Excess amylin, often concurrent with insulin resistance and diabetes, tends to self-dimerize, forming fibrils. These fibrils may interact with beta-amyloid in the brain, potentially contributing to amyloid plaque formation, although a definitive causal relationship remains elusive.

What Is Cagrilintide?

Cagrilintide is a synthetic analogue of the natural peptide amylin. Engineered to resist degradation by blood proteases, it has an extended half-life. Cagrilintide is not the first amylin analogue; pramlintide, developed earlier in the 21st century, was established as an insulin adjunct that reduces postprandial glucose spikes, thereby improving blood sugar control. Cagrilintide distinguishes itself from pramlintide primarily through its significantly longer half-life.

Beyond extending amylin’s half-life, cagrilintide also prevents a common issue of natural amylin: protein aggregation. Excess amylin in the bloodstream can aggregate into amyloid fibrils, which are toxic to pancreatic beta cells and implicated in type 2 diabetes development. This aggregation is hypothesized to result from excessive food intake leading to increased insulin and amylin release, producing toxic amylin tangles similar to the amyloid-beta tangles in Alzheimer’s disease. These tangles contribute to beta cell death and impaired insulin production.

Cagrilintide represents advanced peptide engineering designed to overcome the limitations of natural amylin, which is unsuitable for exogenous administration due to fibril formation tendencies. Scientists improved cagrilintide by adding proline residues at the C-terminal end to reduce aggregation, an amide group to enhance receptor binding, and a fatty acid residue at the N-terminal end to increase brain penetration. These modifications improve binding at RAMP-1 and RAMP-3 receptors.

RAMPs (receptor activity-modifying proteins) are proteins that modulate G-protein coupled receptors’ function. RAMP-1 and -3 interact with calcitonin-like receptors, calcitonin receptors, and calcium-sensing receptors, while RAMP-3 also interacts with the secretin receptor. Although the exact consequences of these interactions are not fully understood, RAMP dysfunction is implicated in diseases such as cardiovascular disease, diabetes, and cancer.

How Does Cagrilintide Work?

Cagrilintide slows food transit through the stomach and intestines, stimulating the gastrointestinal tract to signal fullness to the brain. This reduces hunger and decreases food intake. The slower transit also flattens blood sugar spikes post-meal, allowing better sugar processing and less conversion to fat.

In the central nervous system, cagrilintide binds to abundant amylin receptors in the arcuate nucleus of the brain. This binding affects the brainstem and pituitary gland, promoting satiety and reducing food consumption drive.

Finally, cagrilintide acts on the pancreas in a feedback loop, reducing glucagon release and thus lowering glucose conversion to fat.

Cagrilintide: The Research on Obesity

Two major trials highlight cagrilintide’s effects. Administered once weekly, cagrilintide led to 6–11% total body weight loss over six weeks compared to placebo, exceeding weight loss observed with liraglutide, which served as a positive control. Side effect rates were similar between cagrilintide and liraglutide.

In a second trial, combining cagrilintide with semaglutide produced synergistic weight loss effects greater than either drug alone, reaching up to 17.1% weight loss over 20 weeks. For example, a 17% weight loss for a 200-pound individual equals 34 pounds lost in just five months.

Cagrilintide in Diabetes

Cagrilintide and related agents like pramlintide reduce insulin resistance and lower hemoglobin A1C by inhibiting glucagon secretion. Studies show reductions in A1C of approximately 2.2% over short periods.

Cagrilintide’s once-weekly administration improves acceptability and effectiveness by providing sustained blood sugar control and appetite suppression.

Cagrilintide in Alzheimer’s Disease

The connection between blood sugar regulation and cognitive dysfunction is well-established. Diabetes associates with impaired memory, attention, and processing speed even in younger people. Hyperglycemia may activate protein kinase C, damaging brain cells, and increase inflammation and oxidative stress, contributing to cognitive decline and complications like heart and kidney disease.

Longitudinal studies correlate chronic high blood sugar with increased risk of mild cognitive impairment and dementia. Research indicates that brain insulin resistance and impaired glucose utilization, despite high blood sugar, play key roles in dementia development.

Amylin levels also link to cognitive function. The Framingham Heart Study shows a U-shaped relationship where both low and high amylin levels associate with increased cognitive dysfunction and Alzheimer’s risk.

Previously, Alzheimer’s was sometimes called “type 3 diabetes” due to its metabolic features. The shared structural features and receptors of amylin and beta amyloid—major components of amyloid plaques—suggest a link. High amylin may form crosslinks in blood, preventing it from crossing the blood-brain barrier, allowing beta amyloid buildup. Mouse models show synthetic amylin administration reduces brain amyloid plaques and increases blood amylin levels.

This evidence suggests amylin’s significant role in cognitive dysfunction. Though research is ongoing, cagrilintide and similar peptides may become therapeutic or preventive agents for Alzheimer’s disease, an area ripe for exploration. To date, no published studies have investigated cagrilintide’s role in amyloid clearance or cognitive dysfunction treatment.

Cagrilintide Summary

Cagrilintide is a synthetic analogue of amylin, naturally released by the pancreas. Originally developed for diabetes, it is now repurposed to combat obesity. Like GLP-1 receptor analogues such as semaglutide, it slows gastric motility and promotes satiety. Early research indicates cagrilintide provides more substantial weight loss benefits, especially when combined with semaglutide.

Potential benefits beyond weight loss, including heart disease management and Alzheimer’s treatment or prevention, remain theoretical but promising. This research area is open and actively pursued.

Research Applications

Cagrilintide is primarily utilized in scientific studies focusing on:

• Weight Management: Investigating its efficacy in reducing body weight and controlling appetite.
• Glycemic Control: Assessing its impact on blood glucose levels and insulin sensitivity.
• Metabolic Health: Exploring its potential to improve metabolic parameters in individuals with obesity or type 2 diabetes.

Product Specifications

• Form: Lyophilized (freeze-dried) powder for reconstitution.
• Dosage: Each vial contains 5mg of Cagrilintide.
• Purity: Typically ≥99%, ensuring high-quality material for research purposes.
• Packaging: Available in sealed vials containing 5mg of Cagrilintide powder.
• Storage: Store lyophilized Cagrilintide at temperatures below -18°C. After reconstitution, store at 4°C and use within 2-7 days.

Safety and Handling

Cagrilintide is intended strictly for laboratory research and is not approved for human consumption. Handle with care, following appropriate safety protocols. Ensure proper storage conditions to maintain the integrity and efficacy of the compound.

Referenced Citations

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