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Metabolic — Amylin AnalogResearch Use

Cagrilintide

Also known as: NN9838 · CagriSema component

MW

3949.57 Da

Amino Acids

37 AA

Half-Life

7 days

Route

SubQ

CAS

2375217-89-5

Mechanism of Action

Cagrilintide is a long-acting acylated amylin analog designed for once-weekly subcutaneous injection. Amylin is a 37-amino acid peptide co-secreted with insulin from pancreatic β-cells.

PRIMARY MECHANISM — AMYLIN RECEPTOR ACTIVATION: Binds amylin receptors (heterodimers of calcitonin receptor [CALCR] with RAMP1, RAMP2, or RAMP3) in the area postrema and hypothalamus. Activation reduces appetite through central satiety signaling — a pathway distinct from and complementary to GLP-1.

GASTRIC EMPTYING: Slows gastric emptying, extending post-meal satiety and reducing postprandial glucose excursions.

GLUCAGON SUPPRESSION: Reduces post-meal glucagon secretion, contributing to glycemic control.

CagriSema COMBINATION: The major clinical development is CagriSema — cagrilintide combined with semaglutide in a single injection. This exploits dual amylin + GLP-1 pathways for additive appetite suppression. Early data suggests ~25% body weight loss — potentially exceeding either agent alone. Phase III REDEFINE trials are ongoing.

The amylin pathway represents a distinct metabolic signaling axis from GLP-1, explaining why combining both produces greater weight loss than maximizing either pathway alone.

Dosing Protocol

Low Dose

███ – ███ mcg/day

Standard Dose

███ mcg/day

High Dose

███ – ███ mcg/day

Dosing protocols are for paid members

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Frequency

Once weekly SubQ.

Half-Life

7 days

Reconstitution Guide

Full reconstitution protocol with BAC water volumes, concentration math, and units-to-draw per dose is available on the Clinical plan.

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Clinical Warnings

Investigational — not yet approved anywhere.

GI side effects (nausea, vomiting) expected.

Same class concerns as pramlintide.

Amylin receptor biology less characterized than GLP-1.

Contraindications

Absolute

Pregnancy

MEN2 syndrome

Personal/family medullary thyroid cancer

Relative Cautions

Gastroparesis

Gallbladder disease

Pancreatitis history

Side Effect Profile

Mild

  • Nausea
  • Injection site reaction
  • Diarrhea

Moderate

  • Vomiting
  • Constipation
  • Abdominal pain

Severe (Rare)

  • Pancreatitis
  • Gallbladder events

Synergistic Peptides

SemaglutideTirzepatide

Common Stacks

Semaglutide

Research Status

PHASE III (REDEFINE trials, NCT05394259). Phase II (PMID 37516273, Lau 2023): Significant dose-dependent weight loss. CagriSema showing ~25% weight loss in combination trials. Not yet FDA approved.

Frequently Asked Questions

How does Cagrilintide work?

Cagrilintide is a long-acting acylated amylin analog designed for once-weekly subcutaneous injection. Amylin is a 37-amino acid peptide co-secreted with insulin from pancreatic β-cells. PRIMARY MECHANISM — AMYLIN RECEPTOR ACTIVATION: Binds amylin receptors (heterodimers of calcitonin receptor [CALCR] with RAMP1, RAMP2, or RAMP3) in the area postrema and hypothalamus. Activation reduces appetite through central satiety signaling — a pathway distinct from and complementary to GLP-1. GASTRIC EMPT

What is the standard dose of Cagrilintide?

Cagrilintide dosing protocols are available with a ClinPep Clinical subscription. Dosing varies by indication and patient factors — consult a licensed healthcare provider. General frequency: Once weekly SubQ.

What is the half-life of Cagrilintide?

The half-life of Cagrilintide is 7 days. This determines optimal dosing frequency and timing.

Who should not use Cagrilintide?

Cagrilintide is absolutely contraindicated in: Pregnancy; MEN2 syndrome; Personal/family medullary thyroid cancer. Use with caution in: Gastroparesis; Gallbladder disease; Pancreatitis history.

What are the side effects of Cagrilintide?

Common mild side effects include: Nausea, Injection site reaction, Diarrhea. Moderate effects: Vomiting, Constipation, Abdominal pain.

What peptides stack well with Cagrilintide?

Cagrilintide is commonly stacked with: Semaglutide, Tirzepatide.

How do you reconstitute Cagrilintide?

Cagrilintide is reconstituted with bacteriostatic water. Exact volumes, concentrations, and units-to-draw calculations are available in the ClinPep Clinical plan. Always follow your compounding pharmacy's instructions.

How long should you cycle Cagrilintide?

Cagrilintide cycle protocols vary by indication. Detailed cycle length, on/off schedules, and monitoring guidelines are available with ClinPep Clinical access. Consult your healthcare provider for personalized cycling guidance.

References & Citations

10 PubMed studies · 3 clinical trials

Amylin receptors as therapeutic targets in obesity: Emerging peptide-based strategies.

Rejili Mokhtar, Hussain Md Sadique, Khan Yumna, Haouala Faouzi et al.. Vascular pharmacology. 2026

PubMed: 41344603DOI ↗C — Research Article

Obesity is a chronic, relapsing metabolic disorder driven by complex genetic and environmental factors, leading to an imbalance in energy regulation. Despite the presence of GLP-1 receptor agonists wi

CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1.

Verma Subodh, Böttcher Morten, Brown Paul, Dicker Dror et al.. Hypertension (Dallas, Tex. : 1979). 2026

PubMed: 41328546DOI ↗C — Research Article

Fixed-dose combination of semaglutide/cagrilintide (CagriSema 2.4 mg/2.4 mg) has demonstrated significant and clinically relevant body weight reductions in adults with overweight or obesity compared w

Synthetic target trial emulation and predictive modeling of amylin-pathway therapies for obesity and type 2 diabetes.

Al-Harbi Faisal A, Alsaif Ahmed K, Almutairi Atheer G, Alshehri Hussam J et al.. Metabolism open. 2025

PubMed: 41255585DOI ↗C — Research Article

Amylin-pathway therapies represent a novel therapeutic class for obesity and type 2 diabetes, however head-to-head comparative data and long-term outcome predictions remain limited. We conducted targe

Amylin and the renin-angiotensin system: risk or opportunity in amylin-based therapy?

Muskiet Marcel H A, Nardone Massimo, Rensen Patrick C N, Cherney David Z I et al.. Lancet (London, England). 2026

PubMed: 41207308DOI ↗A — High-Impact Journal

We hypothesise that amylin receptor agonists (eg, pramlintide) and dual amylin and calcitonin-receptor agonists (eg, cagrilintide), which are emerging treatments for obesity and type 2 diabetes, can a

Eloralintide (LY3841136), a novel amylin receptor agonist for the treatment of obesity: From discovery to clinical proof of concept.

Briere Daniel A, Qu Hongchang, Lansu Katherine, He Minxia Michelle et al.. Molecular metabolism. 2025

PubMed: 41109426DOI ↗C — Research Article

Eloralintide (LY3841136), a novel amylin analog, was evaluated in translational studies to characterize its therapeutic potential for treating obesity. In vitro assays were performed in cell lines sel

Novel GLP-1-based Medications for Type 2 Diabetes and Obesity.

Son Jang Won, le Roux Carel W, Blüher Matthias, Nauck Michael A et al.. Endocrine reviews. 2026

PubMed: 41054801DOI ↗C — Research Article

The approvals of semaglutide and tirzepatide have set new benchmarks in the treatment of type 2 diabetes and obesity. Building on their success, novel glucagon-like peptide-1 (GLP-1)-based therapeutic

Weight management treatment in obesity.

Rubio-Herrera Miguel A, Mera-Carreiro Sara. Medicina clinica. 2025

PubMed: 40865172DOI ↗C — Research Article

Obesity is a chronic and relapsing disease associated with medical complications and mortality. Our improved understanding of the relevance of the gut-brain axis in regulating appetite and body weight

Structural and mechanistic insights into dual activation of cagrilintide in amylin and calcitonin receptors.

Gu Yi-Min, Yuan Qing-Ning, Li Xin, He Qian et al.. Acta pharmacologica Sinica. 2026

PubMed: 40847076DOI ↗C — Research Article

The global obesity epidemic and its associated metabolic disorders urgently require more effective therapeutic interventions, particularly multi-pathway targeting therapies. Cagrilintide (Cagri), func

Registered Clinical Trials

A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Tirzepatide in People With Type 2 Diabetes Treated With Metformin With or Without an SGLT2 Inhibitor

NCT06221969ACTIVE_NOT_RECRUITINGPHASE3

A Research Study to See How Well CagriSema Helps People in East Asia With Excess Body Weight Lose Weight

NCT05813925COMPLETEDPHASE3

A Research Study to See How Well CagriSema Helps People With Excess Body Weight Lose Weight

NCT05567796ACTIVE_NOT_RECRUITINGPHASE3

Symptom Indications

ObesityType 2 diabetesInsulin resistanceAppetite control

Full Clinical Access

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This information is for educational and research reference purposes only. ClinPep does not provide medical advice, diagnosis, or treatment recommendations. All protocols should be reviewed by a licensed healthcare provider.