Cagrilintide CGL

# Cagrilintide (Code Name: AM833)

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> ⚠️ Important Notice: Cagrilintide is a peptide currently in clinical development and has not yet been approved for marketing by the FDA or EMA. For research use only; not to be used as a therapeutic drug in humans.
## Basic Information

– Product Name: Cagrilintide
– Code Name: AM833; Name of the combination product: CagriSema = Cagrilintide + Semaglutide
– CAS Number: 1415456-99-7
– Amino Acids: A 37-amino acid synthetic peptide with an intramolecular disulfide bond formed by two cysteine residues
– Category: DACRA (Dual Amylin and Calcitonin Receptor Agonist), a dual agonist of the amylin and calcitonin receptors
– Developer: Novo Nordisk
– Half-life: 7–10 days; designed for once-weekly subcutaneous injection
– Appearance: White to off-white lyophilized powder
– Solubility: Sparingly soluble in pure water; commonly reconstituted with dilute acetic acid
– Storage: Lyophilized powder—store at -20°C, protected from light and in a sealed container; after reconstitution, may be stored at 2–8°C for a short period
– Shelf life: 24 months (when stored properly)

## Structural Features

The backbone is derived from pramlintide and has been modified to include several optimizations compared to natural human incretin:

1. Three proline substitutions have been introduced to eliminate the amyloid aggregation tendency of natural IAPP, reducing the risk of fibrosis
2. An E14/R17 salt bridge stabilizes the α-helix structure and enhances receptor affinity
3. N-terminal long-chain fatty acid lipidation modification extends the in vivo half-life, enabling once-weekly dosing
4. Simultaneously activates the amylin receptor complex and the calcitonin receptor, making it a dual receptor agonist

## Mechanism of Action (Scientific / Clinical Trial Mechanism)

Amylin is an endogenous hormone secreted synchronously with insulin by pancreatic β-cells. Cagrilintide mimics and amplifies the physiological effects of amylin:

1. Slows gastric emptying, prolongs the feeling of fullness, and reduces the amount consumed per meal
2. Triggers central satiety signals in the posterior brainstem, suppressing the desire for reward-seeking eating
3. Inhibits postprandial glucagon release, stabilizing postprandial blood glucose levels
4. Regulates energy metabolism, reducing fat accumulation

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> CagriSema: Cagrilintide (amylin pathway) + Semaglutide (GLP-1 pathway). The synergistic combination of these two appetite-regulating pathways results in weight loss effects in clinical trials that are significantly stronger than those of monotherapy PMC

## Clinical Research Focus (Trial data only; not a guarantee of efficacy)

1. Obese/overweight individuals: Phase II/III REDEFINE series trials demonstrated that weekly subcutaneous monotherapy significantly reduced body weight; CagriSema combination therapy showed even greater weight loss efficacy
2. Type 2 Diabetes: In the Phase III REIMAGINE series of trials, it simultaneously improved HbA1c and body weight, making it suitable for obese patients with diabetes

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> Most common adverse reactions: Gastrointestinal reactions (nausea, diarrhea, constipation, vomiting), mostly mild to moderate; followed by local injection site reactions
## Regulatory Status

– FDA/EMA: CagriSema is under review and has not yet been approved for marketing; Cagrilintide as a monotherapy remains in the clinical research phase, with no marketed products
For research use only; human clinical and therapeutic use is prohibited