Cagrilintide Research: The Long-Acting Amylin Analogue and What Its Trials Investigated

What is cagrilintide?

What is cagrilintide? It is a synthetic, lipidated, long-acting analogue of amylin — also called islet amyloid polypeptide, the pancreatic hormone co-secreted with insulin from beta cells. Kruse et al. (2021, J Med Chem) report its development and identify it as analogue 23 in a structure–activity campaign, selected for clinical development with obesity as the studied indication.

The commonest misunderstanding about this compound is worth correcting immediately: cagrilintide is not a GLP-1 receptor agonist. It is not an incretin, not a dual or triple agonist, and it engages neither GLP-1R, GIPR nor the glucagon receptor. It appears in the same conversations as those molecules because it has been studied alongside semaglutide, not because it shares a mechanism with it. Material referenced here is a laboratory synthetic in lyophilized powder form: not a medicine, not for human use.

Discovery and origin: the amyloid problem

Amylin has been known for decades, and the reason a long-acting analogue took so long is stated bluntly in the development paper’s first line: a hallmark of amylin is its high propensity toward the formation of amyloid fibrils, which makes it a challenging drug-design effort. A peptide that aggregates into fibrils is hard to formulate, keep in solution and characterise — a chemistry problem before a pharmacology one.

The prior art was pramlintide, an amylin analogue available as an adjunct to insulin therapy, which Kruse et al. note requires three daily injections because of its short half-life. Cagrilintide was built to be stable and long-acting instead: a lipidated analogue whose acyl chain performs the same albumin-binding trick used in the GLP-1 class, on a different hormone backbone. That parallel strategy — not a shared receptor — is the real family resemblance here.

Reference data

Drawn from the public chemical record (PubChem CID 171397054) and the development literature. Fields that could not be sourced — including the full residue sequence — are omitted rather than estimated.

One detail is worth noting: the two sulfur atoms in the formula are consistent with the intramolecular disulfide bridge amylin carries near its N-terminus — an analytically fragile feature the verification section returns to.

Mechanism — amylin receptors are assemblies, not proteins

The cagrilintide mechanism literature is unusual because the target itself is unusual. Each line below is what researchers characterised in model systems, not an effect in any reader:

• The calcitonin receptor plus a RAMP — Carvas et al. (2025, EBioMedicine) state the architecture plainly: amylin binds a heterodimer of the calcitonin receptor (CTR) with one of the receptor activity-modifying proteins RAMP1, RAMP2 or RAMP3, producing the receptors labelled AMY1, AMY2 and AMY3. There is no single gene for an “amylin receptor.”
• Dual amylin and calcitonin receptor agonism — because CTR is part of the assembly, agonists of this class engage the calcitonin receptor too; Carvas et al. describe cagrilintide and salmon calcitonin as dual amylin–calcitonin receptor agonists.
• Receptor dependency tested by knockout — in RAMP1/3 knockout mice, Carvas et al. reported that the absence of RAMP1 and RAMP3 impeded cagrilintide’s potency, concluding that its body-weight effect in that model depends on AMY1R and AMY3R. Both peptides studied also activated cFos signal in neurons of the dorsal vagal complex and lateral parabrachial nucleus in wild-type mice — brainstem regions, where the mechanistic interest in this class currently sits.

This is a genuinely different mechanistic story from the incretin peptides in the research library. Where survodutide and mazdutide extend the GLP-1 receptor story by adding the glucagon receptor, cagrilintide leaves that family entirely. The incretin comparison lives on the comparison page, and cagrilintide is not on it.

Cagrilintide alone, and cagrilintide with semaglutide

The published programme splits cleanly into two lines, and conflating them is the biggest error in secondary coverage of this compound.

Cagrilintide as a single agent

• Lau et al., 2021 (Lancet, PMID 34798060) — a multicentre, randomised, double-blind, placebo-controlled and active-controlled dose-finding phase 2 trial in people with overweight and obesity. The active control was liraglutide 3.0 mg, making this a direct point of contact between the amylin and GLP-1 literatures.

CagriSema — the coadministered combination

• Enebo et al., 2021 (Lancet, PMID 33894838) — a phase 1b trial examining safety, tolerability, pharmacokinetics and pharmacodynamics when multiple doses of cagrilintide were given concomitantly with semaglutide 2.4 mg; the first study in the combination line.
• Frias et al., 2023 (Lancet, PMID 37364590) — a randomised, active-controlled phase 2 trial of the co-administered pair in people with type 2 diabetes.
• Garvey et al., 2025 (NEJM, PMID 40544433) — REDEFINE 1, the phase 3 trial of coadministered cagrilintide and semaglutide in adults with overweight or obesity.
• Davies et al., 2025 (NEJM, PMID 40544432) — REDEFINE 2, the phase 3 counterpart in adults with overweight or obesity and type 2 diabetes.

None is reported here with outcome figures. What matters for a reference page is the shape of the evidence: the single-agent literature is a phase 2 dose-finding trial, while the phase 3 programme studied the combination. REDEFINE was not designed to answer what cagrilintide does on its own and should not be read as though it were.

Evidence status, regulatory status, and what is not established

What is established: the molecule’s development history and the structure–activity reasoning behind its selection (Kruse 2021); the receptor architecture it acts through and, in a knockout mouse model, its dependency on AMY1R and AMY3R (Carvas 2025); and randomised trials of both the single agent and the combination, run by the manufacturer and published in The Lancet and the New England Journal of Medicine.

What is not established, and is deliberately not claimed here: (1) anything about cagrilintide as a supplied research reagent, since the trials used a manufactured pharmaceutical under medical supervision; (2) any separation of cagrilintide’s contribution from semaglutide’s inside the CagriSema phase 3 data, which those designs were not built to isolate; and (3) any long-term safety characterisation of the single agent, whose published clinical literature remains phase 2 in scope.

On status: cagrilintide is investigational — not approved as a standalone medicine by the FDA, the EMA, BPOM (Indonesia) or any other regulator. Novo Nordisk announced in December 2025 that it had submitted a New Drug Application to the FDA for CagriSema on the basis of the REDEFINE programme — a regulatory submission, which is not an approval and does not become one by being reported. The current national register is the authority, not a reference page. Compare semaglutide, which is approved, and survodutide, which like cagrilintide is not. This page reports no outcome, makes no efficacy or benefit claim, gives no dosing guidance, and describes material that is not for human or veterinary use.

How to verify this compound yourself

Cagrilintide is a large, lipidated, disulfide-containing peptide, which means identity and purity testing has to do more than confirm a mass:

• HPLC purity — reversed-phase chromatography separates the target from related impurities and reports purity as a percentage of the chromatogram. Aggregated or fibrillar material is exactly the failure mode this hormone family’s chemistry predicts, and it does not behave like clean peptide on a column.
• Mass-spec identity — mass spectrometry confirms the measured mass against the expected molecular weight (≈ 4409 Da). Two checks matter: a missing acyl chain shifts the mass downward, and a reduced disulfide adds two hydrogen mass units relative to the closed form.
• Endotoxin / sterility — where tested, separate quality attributes reported independently of chemical purity.

See how to read a COA, how to verify peptide purity, and how to spot a fake COA. Check the exact batch on the self-serve verify tool.

Research-grade sourcing and verification

Cagrilintide is not held in Cellworks stock. It appears in the sourcing catalogue as available to order: our supplier lists it, we have not bought it, and sourcing takes roughly two to three weeks. No price is quoted until availability is confirmed, and there is no cart button.

Anything sourced this way is a laboratory research reagent with a per-batch Certificate of Analysis reporting HPLC purity (%) and mass-spectrometry identity. No combination product is described or supplied — “CagriSema” names a trial intervention here and nothing else.

Frequently asked questions

Literature cited

1. Kruse T, Hansen JL, Dahl K, et al. “Development of Cagrilintide, a Long-Acting Amylin Analogue.” J Med Chem. 2021;64(15):11183–11194. PMID 34288673. pubmed.ncbi.nlm.nih.gov/34288673.
2. 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.” Lancet. 2021;398(10317):2160–2172. PMID 34798060. pubmed.ncbi.nlm.nih.gov/34798060.
3. 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.” Lancet. 2021;397(10286):1736–1748. PMID 33894838. pubmed.ncbi.nlm.nih.gov/33894838.
4. Frias JP, Deenadayalan S, Erichsen L, et al. “Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trial.” Lancet. 2023;402(10403):720–730. PMID 37364590. pubmed.ncbi.nlm.nih.gov/37364590.
5. Garvey WT, Blüher M, Osorto Contreras CK, et al. “Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity.” (REDEFINE 1) N Engl J Med. 2025;393(7):635–647. PMID 40544433. pubmed.ncbi.nlm.nih.gov/40544433.
6. Davies MJ, Bajaj HS, Broholm C, et al. “Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes.” (REDEFINE 2) N Engl J Med. 2025;393(7):648–659. PMID 40544432. pubmed.ncbi.nlm.nih.gov/40544432.
7. Carvas AO, Leuthardt A, Kulka P, et al. “Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3.” EBioMedicine. 2025;118:105836. PMID 40609154. pubmed.ncbi.nlm.nih.gov/40609154.
8. National Center for Biotechnology Information. “PubChem Compound Summary for CID 171397054, Cagrilintide.” pubchem.ncbi.nlm.nih.gov/compound/171397054 (formula, mass, CAS 1415456-99-3).