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Cagrilintide
MetabolicCagrilintide (Long-Acting Amylin Receptor Agonist)
Overview
Cagrilintide is a long-acting acylated amylin analogue developed by Novo Nordisk for once-weekly subcutaneous injection. It selectively activates amylin receptors (AMY1/2/3) in the brainstem and hypothalamus, driving satiety independent of the GLP-1 pathway, slowing gastric emptying, and suppressing postprandial glucagon. Studied standalone and in combination with semaglutide (CagriSema / REDEFINE trials), it produces dose-dependent weight loss with a favorable tolerability profile relative to GLP-1 agonists alone.
Mechanism of Action
Cagrilintide binds amylin receptors (calcitonin receptor heterodimers with RAMP1/2/3) in the area postrema and nucleus tractus solitarius, triggering satiety signaling via a distinct neuronal circuit from GLP-1 — which is why it shows additive effects with GLP-1 agonists. It slows gastric emptying via vagal pathways, suppresses postprandial glucagon in a glucose-dependent manner, may enhance leptin sensitivity, and its C18 fatty di-acid acylation enables reversible albumin binding for a ~7-day half-life and stable weekly dosing.
Research Contexts
Obesity / weight management • Appetite & satiety regulation • Body composition (fat mass reduction with lean-mass preservation) • Glycemic control (fasting glucose, HbA1c) • Combination with GLP-1 receptor agonists (CagriSema)
Dosing (PepPal Protocol)
PepPal only publishes dosing from our vetted protocol PDFs. For peptides without an official PepPal protocol, see the Protocols page.
Weekly SC titration: 0.25 mg (wk 1–4) → 0.50 mg (wk 4–8) → 1.0 mg (wk 8–12) → 1.7 mg (wk 12–16) → 2.0 or 2.4 mg (wk 16+ maintenance). See the full Cagrilintide protocol at /protocol/cagrilintide.
Reconstitution Guide
Vial size: 5 mg
Water volume: 1 mL bacteriostatic water
Concentration: 5 mg/mL (5,000 mcg/mL) — 1 mg = 20 units on a 100U insulin syringe
Bring vial and bac water to room temperature. Wipe tops with alcohol. Inject bac water slowly down the side of the vial — do not agitate. Gently roll (do not shake) until fully dissolved. Solution should be clear and colorless — discard if cloudy or particulate. Once weekly SC (abdomen, thigh, or upper arm). Rotate sites weekly.
Storage Guidelines
Before reconstitution: Refrigerate at 2–8°C. Do not freeze.
After reconstitution: Refrigerate at 2–8°C. Stable for up to 28 days. Do not freeze.
Half-Life & Stability
Half-life: Approximately 7 days — enables true once-weekly dosing
Stability: Generally stable when refrigerated for the 28-day reconstituted window. Slower titration (extending phases 2–4 weeks if GI symptoms appear) markedly improves long-term tolerability.
