Cagrilintide is a long-acting synthetic amylin analog that reduces appetite and slows gastric emptying through central amylin receptors — and in combination with semaglutide (CagriSema), is producing some of the most significant weight loss results in clinical trials.
This peptide profile is for research and educational purposes only. Not intended for human use or self-administration.
Overview
Cagrilintide is a synthetic analog of amylin (Islet Amyloid Polypeptide, IAPP) — the peptide co-secreted with insulin by pancreatic beta cells to regulate post-meal satiety. Natural amylin has a half-life of only minutes, making it impractical as a therapeutic. Cagrilintide was engineered by Novo Nordisk with modifications that extend its half-life to approximately 7 days, allowing once-weekly subcutaneous injection. It acts centrally to reduce food intake, suppress glucagon, and slow gastric emptying — complementary but distinct pathways from GLP-1 receptor agonists, which is why the combination (CagriSema) produces greater weight loss than either alone.
Mechanism of Action
Cagrilintide binds to amylin receptors (CALCR + RAMP1/2/3 heterodimers) in the area postrema and nucleus of the solitary tract — brain regions that regulate satiety and energy homeostasis. Amylin receptor activation reduces meal size, slows gastric emptying (prolonging post-meal fullness), and suppresses post-prandial glucagon (which would otherwise drive glucose production after eating). These effects are additive to GLP-1 receptor agonism: GLP-1 analogs primarily act on the gut and vagal nerve, while amylin analogs act more centrally on brainstem satiety circuits. Cagrilintide also appears to modulate body weight setpoint regulation via hypothalamic pathways.
Key Research
Cagrilintide has completed Phase 1 (safety, PK) and Phase 2 (efficacy) clinical trials with Novo Nordisk. Phase 2 data showed dose-dependent weight loss of up to 10.8% over 26 weeks as a monotherapy. The SCALE NEXT trial combining cagrilintide 2.4 mg + semaglutide 2.4 mg (CagriSema) demonstrated 15.6% weight loss at 32 weeks in Phase 2 — substantially greater than either alone. Phase 3 REDEFINE trials are ongoing with CagriSema as a potential best-in-class obesity therapy. Safety profile is similar to amylin and GLP-1 analogs: primarily GI-related adverse events.
Cagrilintide is escalated gradually to reduce GI side effects: starting at 0.3 mg weekly, increasing in monthly steps to the target dose (up to 4.5 mg in clinical trials, with 2.4 mg appearing to be the practical target in combination protocols). Injected subcutaneously once weekly, it can be administered on the same day as semaglutide in CagriSema combination protocols. This is a pharmaceutical-grade compound; research use should occur within the context of appropriate oversight.
CagriSema Combination Protocol (research): Cagrilintide 2.4 mg SC weekly + Semaglutide 2.4 mg SC weekly, co-administered on the same day, with gradual dose escalation over 16–20 weeks to target dose. This combination is being studied as potentially the most effective pharmacological obesity intervention available. Standalone satiety research: Cagrilintide 0.3–1.2 mg weekly for appetite modulation research without GLP-1 coadministration.
Reported Side Effects
Side effects summarized from animal studies and researcher community observations. Educational purposes only — not medical advice.
GI adverse events — nausea, vomiting, diarrhea, constipation — are the most common side effects, occurring in the majority of subjects during dose escalation and typically diminishing at steady state. The incidence and severity are similar to those seen with GLP-1 agonists. Injection site reactions are mild and transient. Gallbladder effects (similar to GLP-1 class) include increased gallstone risk with rapid weight loss — relevant for extended high-dose protocols. Hypoglycemia risk is low without concurrent insulin use. Tachycardia, which is a concern with some GLP-1 analogs, has not been prominently reported with cagrilintide.
Storage & Handling
Store at 2–8°C (refrigerator). Do not freeze. Protect from light. As with GLP-1 analogs, pre-filled pens or vials should be stored per manufacturer instructions. If removed from refrigeration, it can be stored at room temperature (below 30°C) for up to 4 weeks. Do not shake or expose to extreme temperatures.
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