Cagrilintide

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Cagrilintide is built on a pramlintide-like 37-residue backbone rather than on native human amylin. This is a deliberate design choice: human amylin is prone to amyloid fibril formation, and building from the pramlintide scaffold avoids that liability while retaining full receptor agonist activity.

N-terminal acylation with a C20 eicosanedioic fatty diacid, attached through a gamma-glutamic acid linker. The diacid promotes reversible albumin binding, which is the basis of the compound's extended duration of action.

Intramolecular disulfide bridge.

Reported elimination half-life of 159–195 hours, described in Novo Nordisk trial documentation as approximately 180 hours — a profile supporting once-weekly subcutaneous administration.

Cagrilintide is characterized as a non-selective agonist across the calcitonin receptor family.

AMY1R amylin receptor 1 — calcitonin receptor + RAMP1 AMY2R amylin receptor 2 — calcitonin receptor + RAMP2 AMY3R amylin receptor 3 — calcitonin receptor + RAMP3 CTR calcitonin receptor, unmodified

Amylin receptors are not distinct gene products. They are heterodimers formed when the calcitonin receptor associates with one of three receptor activity-modifying proteins (RAMP1, RAMP2, RAMP3). That architecture is why an amylin analog inevitably engages the calcitonin receptor as well, and why cagrilintide is described in the literature as a dual amylin and calcitonin receptor agonist rather than a selective amylin agonist.

In receptor assays, cagrilintide couples primarily to Gs and cyclic AMP signaling.

Preclinical work localizes activity to the area postrema and the hypothalamus — brain regions associated with satiation signaling and energy-balance regulation.

Cryo-EM and molecular dynamics work has characterized cagrilintide binding to both calcitonin and amylin receptors, describing the structural basis of its non-selective profile (Cao et al., Nature Communications, 2025).

Trial NN9838-4433. A 26-week randomized, double-blind, placebo-controlled and active-controlled trial in 706 adults with obesity or overweight plus at least one weight-related comorbidity.

Participants received once-weekly subcutaneous cagrilintide at 0.3, 0.6, 1.2, 2.4 or 4.5 mg, placebo, or once-daily liraglutide 3.0 mg, alongside lifestyle intervention.

Reported outcomes at week 26, from a baseline of approximately 100 kg: cagrilintide 4.5 mg 10.8% weight reduction cagrilintide 2.4 mg 9.7% weight reduction placebo 3.0% weight reduction

All cagrilintide doses exceeded placebo on the primary endpoint.

The most frequently reported adverse events were gastrointestinal and injection-site reactions, characterized as non-serious and mild to moderate.

(Lau et al., The Lancet, 2021)

A randomized controlled trial examining safety, tolerability, pharmacokinetics and pharmacodynamics of multiple doses of cagrilintide administered concomitantly with semaglutide 2.4 mg.

(Enebo et al., The Lancet, 2021)

CagriSema is a fixed co-formulation of cagrilintide 2.4 mg with semaglutide 2.4 mg. It is two distinct peptides rather than a single molecule, and therefore has no single CAS number, molecular formula, or molecular weight. Semaglutide is a separate compound with its own identity: CAS 910463-68-2, molecular weight approximately 4113.6 g/mol.

Phase 3 REDEFINE programme results as reported: REDEFINE 1 22.7% weight reduction at 68 weeks, adults with obesity REDEFINE 2 13.7% weight reduction, adults with type 2 diabetes

A Phase 3 trial in adults with type 2 diabetes examined the combination in that population (NCT04982575).

(Garvey et al., New England Journal of Medicine, 2025)

Work comparing cagrilintide with other dual amylin and calcitonin receptor agonists has examined whether the relative balance of amylin versus calcitonin receptor activity affects metabolic outcomes in preclinical models.

(Larsen et al., Biomedicine & Pharmacotherapy, 2022)

Reviews of amylin's role in feeding and satiation provide the physiological context for this compound class.

(Lutz, Neuropharmacology, 2025)

Class amylin analog GLP-1 agonist GLP-1/GIP dual agonist Receptor targets AMY1/2/3R + CTR GLP-1R GLP-1R + GIPR Pathway count single (amylin) single (GLP-1) dual CAS 1415456-99-3 910463-68-2 — Molecular weight 4409.01 g/mol ~4113.6 g/mol — Research value isolates amylin reference GLP-1 multi-incretin receptor pathway pathway signaling interaction

Literature on one of these compounds does not transfer to the others.

Cagrilintide is an investigational compound. It is not approved for any indication by the FDA, EMA, or any other regulatory agency, either as monotherapy or as part of the CagriSema combination.

Material supplied for laboratory use is a research chemical. It is not a drug, food, cosmetic, or dietary supplement, has not been evaluated by the FDA, and is not intended for human or veterinary use.