Amylin AnalogOnce-Weekly SCCagriSema Phase 3Area PostremaPramlintide Successor
Cagrilintide is a long-acting amylin analog with a 7-day half-life, designed to address the short half-life limitation of native amylin (minutes) and first-generation pramlintide (3-hour, three-times-daily SC dosing). Amylin is co-secreted with insulin from pancreatic β-cells and acts on area postrema/NTS amylin receptors to suppress glucagon, slow gastric emptying, and reduce meal size — a satiety pathway mechanistically distinct from GLP-1R. The clinical interest in cagrilintide centres on CagriSema (cagrilintide + semaglutide 2.4mg), which produced 22.4% weight reduction in Phase 1b — greater than either agent alone — by combining two non-overlapping satiety pathways.
~168 hr
Half-life — once-weekly dosing
22.4%
Weight reduction CagriSema Phase 1b
~8%
Weight reduction cagrilintide monotherapy Phase 2
STEP-DUO
Ongoing Phase 3 trial with semaglutide
≥99%
Purity — HPLC verified
Cagrilintide — Specifications
Cagrilintide — specifications
Property
Value
CAS Number
2381644-89-1
Molecular Formula
C₁₆₀H₂₆₁N₄₅O₄₈S
Molecular Weight
3682.1 g/mol
Half-life
~168 hr (7 days, SC)
Class
Long-acting amylin analog
Purity
≥99% HPLC verified
COA
Janoshik independent third-party
⚙️
Mechanism of Action — Cagrilintide
Cagrilintide activates amylin receptors (AMY1R, AMY2R, AMY3R) — heterodimers of calcitonin receptor (CTR) with receptor activity-modifying proteins (RAMP1-3). Primary sites:
Area postrema/NTS (brainstem): Primary satiety signalling centre — reduces meal size and frequency independently of GLP-1R
Liver: Reduced hepatic glucose output via glucagon suppression
Why amylin + GLP-1R is mechanistically synergistic
GLP-1R agonists suppress appetite primarily via hypothalamic POMC/AgRP pathways and gastric emptying. Amylin analogs act primarily via area postrema/NTS brainstem circuits. These are anatomically and mechanistically distinct pathways — combining them activates both simultaneously without mutual receptor competition. The CagriSema Phase 1b data (22.4% weight reduction vs ~15% semaglutide alone) provides clinical evidence for this additive mechanism. It is one of the clearest examples in obesity pharmacology of genuine mechanistic synergy rather than additive receptor occupancy.
Up to 10.8% weight reduction at highest dose vs 3.0% placebo
CagriSema Phase 1b 2023
Semaglutide 2.4mg + cagrilintide 2.4mg, 20 weeks
22.4% weight reduction — greater than either alone
STEP DUO Phase 3
Ongoing — CagriSema vs semaglutide vs cagrilintide monotherapy
Primary: body weight % change at 68 weeks
Research Protocols — Cagrilintide
Protocol 1: DIO mouse — amylin monotherapy
0.5–2 nmol/kg SC once weekly × 8 weeks. Body weight, fat mass (EchoMRI), food intake, glucose tolerance (OGTT), plasma glucagon.
Protocol 2: CagriSema combination arm
Cagrilintide 1 nmol/kg + semaglutide 30 nmol/kg vs either alone in DIO mice. All same endpoints — isolates synergy of dual pathway activation.
Protocol 3: Area postrema mechanistic study
c-Fos immunohistochemistry in area postrema and NTS following cagrilintide SC. Compare with GLP-1R agonist activation pattern — maps non-overlapping neuroanatomical targets.
Protocol 4: Gastric emptying
Cagrilintide SC 1hr pre-meal in lean rats. Acetaminophen absorption assay as proxy for gastric emptying rate. Compare with GLP-1R agonist.
Protocol 5: Leptin sensitisation
Cagrilintide in diet-induced leptin-resistant mice. Leptin-induced weight loss response before/after cagrilintide priming — tests amylin resensitisation of leptin signalling.
❓
Frequently Asked Questions
What is cagrilintide?
Cagrilintide is a long-acting synthetic amylin analog with a 7-day half-life, developed by Novo Nordisk. It activates amylin receptors in the area postrema and hypothalamus to suppress appetite and slow gastric emptying — a mechanism distinct from GLP-1R agonists.
What is CagriSema?
CagriSema is the investigational co-formulation of cagrilintide 2.4mg and semaglutide 2.4mg, given as a single once-weekly SC injection. Phase 1b data showed 22.4% weight reduction in 20 weeks — exceeding either agent alone — by activating both amylin and GLP-1R pathways simultaneously.
How does amylin differ from GLP-1R in satiety signalling?
GLP-1R agonists act primarily through hypothalamic POMC/AgRP pathways and vagal GLP-1R. Amylin analogs act primarily through area postrema/NTS brainstem circuits. The two pathways are anatomically distinct, allowing genuine mechanistic combination without receptor competition.
What formats does QSC supply for cagrilintide research?
QSC supplies cagrilintide as lyophilised research vials, ≥99% purity confirmed by HPLC with Janoshik COA. Ships domestically from QSC warehouses in the USA, EU, UK, Canada, and Australia.
Is cagrilintide FDA approved?
Cagrilintide is in Phase 3 trials (STEP DUO) as of 2025. It is not yet approved by the FDA or equivalent bodies. QSC supplies it for laboratory research purposes only.
Research Use Only: All QSC compounds are sold strictly for laboratory research purposes. Not for human use. Not approved by the FDA or equivalent regulatory bodies for human administration. All purchases confirm research intent and compliance with applicable local regulations.
