Cagrilintide

Overview

Cagrilintide — also identified in the literature by its development code AM833 — is a synthetic, long-acting analogue of the pancreatic hormone amylin. It is studied as an amylin receptor agonist in research on appetite signalling, gastric emptying and energy balance, and is one of the few peptides in this catalogue with a substantial, independently reported clinical research record.

Its distinguishing feature is duration. Native amylin is cleared within minutes; cagrilintide is engineered for a half-life measured in days, which is what makes once-weekly administration schedules feasible in the study designs where it appears.

Chemical identity

• CAS number: 1415456-99-3
• Molecular formula: C₁₉₄H₃₁₂N₅₄O₅₉S₂
• Molecular weight: 4409.01 g/mol
• Classification: Amylin analogue, amylin (AMY) and calcitonin (CTR) receptor agonist
• Development code: AM833
• Appearance: White lyophilised powder

At 4,409 g/mol cagrilintide is a large, structurally complex peptide, roughly eleven times the mass of a short bioregulator such as Epithalon. A conventional two-dimensional structure diagram of a molecule this size is a dense tangle of overlapping bonds and labels that conveys nothing at reading size, so this page describes its architecture rather than depicting it.

That architecture has three notable elements. The backbone is a 32-residue peptide based on human amylin, carrying substitutions that suppress the aggregation to which native human amylin is prone. A disulphide bridge near the N-terminus — the source of both sulfur atoms in the formula — closes a ring that is required for receptor binding. And a fatty diacid chain is attached through a linker, which allows the molecule to bind reversibly to circulating albumin. That albumin binding is the mechanism behind its extended duration: bound peptide is protected from renal clearance and released gradually.

The same acylation strategy appears in semaglutide, which is why the two compounds share a dosing cadence despite acting on entirely different receptors.

Amylin, the hormone it is modelled on

Amylin — also called islet amyloid polypeptide, or IAPP — is a 37-residue hormone co-secreted with insulin from pancreatic beta cells in response to nutrient intake. It is a satiety and gastric signal rather than a glucose-lowering one: research describes roles in slowing gastric emptying, suppressing post-meal glucagon secretion, and signalling meal termination through receptors in the hindbrain.

Native human amylin is difficult to work with. It aggregates readily into amyloid fibrils, which is both why it forms deposits in pancreatic tissue and why it cannot simply be synthesised and used as a research analogue. Every amylin analogue of research interest, cagrilintide included, exists because the native sequence had to be re-engineered for solubility and stability.

Mechanism of action

Amylin signals through receptors formed when the calcitonin receptor associates with receptor activity-modifying proteins, producing the AMY₁, AMY₂ and AMY₃ subtypes. Cagrilintide is described in the literature as a non-selective agonist across these amylin receptors and at the calcitonin receptor itself — a broader profile than earlier analogues, and one of the compound’s more actively discussed characteristics.

Downstream, the reported effects are those associated with amylin signalling generally: delayed gastric emptying, reduced food intake, and activation of satiety pathways in the area postrema, a hindbrain region outside the blood–brain barrier that is densely populated with amylin receptors.

Why it is studied alongside GLP-1 receptor agonists

Most current research interest in cagrilintide concerns its use in combination rather than alone, and the reasoning is mechanistic. Amylin and GLP-1 are separate hormones acting on separate receptors through separate pathways, but converging on overlapping outcomes in appetite and gastric regulation. Combining an agonist at each is therefore expected to produce effects greater than either alone, without the receptor competition that would follow from combining two agonists at the same target.

The combination of cagrilintide with semaglutide is studied under the name CagriSema, and is the context in which most published cagrilintide research now appears. For research design purposes, the significant point is that the two compounds are pharmacologically complementary rather than redundant — the reason the pairing is investigated at all.

Research to date

Cagrilintide has a more developed research record than most compounds in this catalogue, having progressed through structured clinical investigation rather than existing only in preclinical work.

• Dose-finding. A randomised phase 2 trial reported by Lau and colleagues examined once-weekly cagrilintide across an ascending dose range over 26 weeks, with both placebo and active comparators, and reported dose-dependent effects on body weight.
• Combination pharmacology. A phase 1b trial reported by Enebo and colleagues examined concomitant administration with semaglutide, characterising the pharmacokinetics and tolerability of the two given together.
• Later-stage work. Subsequent randomised trials have examined the combination in populations with type 2 diabetes, and a phase 3 programme has been reported in the literature.

The practical consequence for a research setting is that pharmacokinetic parameters, dose ranges and tolerability profiles are documented in the peer-reviewed record rather than having to be inferred — unusual among research peptides and worth using when designing experiments.

Reported observations

Across published studies, the effects most consistently reported are gastrointestinal: nausea, reduced appetite and altered gastric motility, generally described as dose-related and most pronounced during dose escalation. Injection-site reactions are also reported. These are the observations that appear in the published record; they are not a complete safety characterisation, and they describe findings in the specific study populations and designs involved.

Handling, reconstitution and storage

Cagrilintide ships as a lyophilised powder. Its size and acylation make it more delicate than the short peptides in this catalogue:

• Lyophilised storage: keep sealed, refrigerated and protected from light. Freezing is appropriate for long-term storage.
• Reconstitution: add diluent slowly down the vial wall and allow the powder to dissolve undisturbed. Do not shake. Acylated peptides are surface-active and foam readily, and foaming denatures them.
• After reconstitution: refrigerate, protect from light, and avoid repeated freeze–thaw cycles. Aliquot if the vial will be drawn on more than a few times.
• Concentration: our peptide reconstitution calculator converts vial quantity, diluent volume and syringe size into concentration per unit.

Purity and analytical verification

A 32-residue acylated peptide is a demanding synthesis. Each coupling step is an opportunity for a deletion sequence, and the acylation and disulphide formation add further points at which a batch can go wrong. Impurities in a peptide this size are therefore often closely related to the target — a peptide missing one residue, or carrying an incomplete modification — which makes them harder to detect than gross contamination.

Two figures are worth checking on any certificate of analysis. HPLC purity quantifies the proportion of material that is the intended peptide. Mass spectrometry confirms identity: a measured mass consistent with 4,409 g/mol distinguishes the correct molecule from a deletion sequence that may elute at a similar retention time. For acylated peptides in particular, mass confirmation matters more than usual, because a batch missing its fatty acid chain would still look broadly correct on a chromatogram while behaving quite differently.

We publish third-party certificates of analysis by batch. If a supplier cannot produce both figures for the specific lot on offer, purity claims are unverifiable.

References

• Lau DCW, Erichsen L, Francisco AM, et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial. The Lancet, 2021. PMID 34798060
• Enebo LB, Berthelsen KK, Kankam M, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial. The Lancet, 2021. PMID 33894838
• Frias JP, et al. Efficacy and safety of co-administered once-weekly cagrilintide with once-weekly semaglutide in type 2 diabetes: a randomised, double-blind, active-controlled, phase 2 trial. The Lancet, 2023. PMID 37364590

Summary

Cagrilintide (AM833) is a long-acting amylin analogue, CAS 1415456-99-3, molecular formula C₁₉₄H₃₁₂N₅₄O₅₉S₂, molecular weight 4,409.01 g/mol. A 32-residue amylin-derived backbone is stabilised against aggregation and acylated with a fatty diacid, giving albumin binding and a duration long enough for weekly dosing schedules. It acts as a non-selective agonist at amylin and calcitonin receptors, with reported effects on gastric emptying, food intake and satiety signalling. Most current research examines it in combination with a GLP-1 receptor agonist, on the reasoning that the two act through complementary and non-competing pathways.

For laboratory research use only. Not for human consumption. This material is not a drug, food, or cosmetic and may not be sold or used for any purpose other than in vitro or non-human laboratory research. References to clinical studies above describe the published scientific literature and are not guidance for use.