Cagrilintide

What cagrilintide is

Cagrilintide is a synthetic, single-chain peptide of 37 amino acids designed as a long-acting analogue of amylin, the pancreatic hormone co-secreted with insulin. It was developed at Novo Nordisk under the codes NN9838 and AM833 (also written NNC0174-0833), and the discovery paper by Kruse and colleagues describes it as "a stable, lipidated, long-acting amylin analogue" selected from a structure–activity programme for clinical development in obesity [1]. It is investigational: it has no marketing authorisation in the United Kingdom or elsewhere, either on its own or in the fixed combination with semaglutide that the sponsor calls CagriSema.

Three design decisions define the molecule, and they are best understood against the two peptides it descends from. Native human amylin is unsuitable as a drug because it forms amyloid fibrils readily in solution [1, 2]. Pramlintide, the one amylin analogue to reach the clinic, solved the fibrillation problem by borrowing three proline residues from rat amylin at positions 25, 28 and 29, but it has a half-life measured in minutes and in clinical use must be injected before each meal [1, 2]. Cagrilintide keeps pramlintide's three prolines and adds two further substitutions in the backbone, asparagine-14 to glutamate and valine-17 to arginine, which the structural literature attributes to a deliberate attempt to resist fibril formation and to stabilise the N-terminal helix through an intramolecular salt bridge [1, 4]. The C-terminal tyrosine of the natural sequence is replaced by proline. Finally, the N-terminal lysine carries a C20 fatty diacid attached through a γ-glutamate linker [4]. That lipid chain binds reversibly to serum albumin and is the source of the long half-life, which in humans was estimated at 159 to 195 hours, or roughly seven to eight days, in the phase 1b study [5].

The molecule retains the disulfide bridge between cysteines 2 and 7 that is conserved throughout the calcitonin peptide family, and the C-terminus is amidated. In its research presentation it is a white to off-white lyophilised powder. The reference identifiers are in the table below.

The CAS number, formula and sequence above correspond to the registered structure as recorded in the FDA substance registration system and PubChem. The molecular weight is the average value calculated from that formula; a certificate may instead report a monoisotopic or deconvoluted electrospray mass, as discussed below.

How the literature describes its mechanism

Amylin, also called islet amyloid polypeptide, is a 37-residue peptide stored in the same secretory granules as insulin in pancreatic β-cells and released with it in response to a meal. It belongs to the calcitonin family alongside calcitonin, calcitonin gene-related peptide and adrenomedullin. The 2015 review by Hay and colleagues summarises its physiology: it slows gastric emptying, suppresses post-prandial glucagon secretion, and reduces food intake through actions in the hindbrain, in particular the area postrema, which lies outside the blood–brain barrier and is accessible to circulating peptides [2].

The receptor pharmacology is unusual and matters for how in-vitro work on cagrilintide is designed. There is no dedicated amylin receptor gene. Christopoulos and colleagues showed in 1999 that amylin receptors arise when the calcitonin receptor (CTR), a class B G-protein-coupled receptor, forms a complex with one of three single-pass membrane proteins called receptor activity-modifying proteins (RAMPs). CTR with RAMP1, RAMP2 or RAMP3 gives the AMY1, AMY2 and AMY3 receptor phenotypes respectively, each with a distinct profile of affinity for amylin, calcitonin and CGRP [3]. The unmodified CTR responds potently to calcitonin and only weakly to amylin, while the RAMP complexes respond strongly to amylin [4]. Any cell-based assay therefore has to specify which complex it expresses, because results at CTR alone and at CTR–RAMP complexes will differ.

Cagrilintide is described in the primary literature as an agonist at both the calcitonin receptor and the amylin receptors, which is why it is sometimes classed as a dual amylin and calcitonin receptor agonist rather than a pure amylin mimetic [1, 4]. In 2025 Cao and colleagues reported cryo-electron microscopy structures of cagrilintide bound to active, Gs-coupled AMY1, AMY2 and AMY3 receptors and to CTR, and compared them with earlier structures of the same receptors bound to rat amylin and salmon calcitonin. They found that cagrilintide adopts an amylin-like binding mode, that its backbone substitutions plausibly account for its improved potency at CTR relative to rat amylin, and that it induces distinct conformational dynamics in the receptor complexes. In their hands the C-terminal proline reduced potency at CTR expressed alone but not in cells co-expressing RAMP3 [4]. The authors suggest these features may contribute to clinical efficacy, but that remains a hypothesis rather than a demonstrated mechanism.

For a laboratory programme, the relevant readouts are cAMP accumulation in cells co-expressing CTR with a chosen RAMP, binding competition against labelled amylin or calcitonin, and fibrillation assays such as thioflavin T fluorescence. Potency figures in the literature depend heavily on which receptor complex and cell background were used, so comparisons across papers should be made with care [1, 4].

The clinical research record

Cagrilintide has been studied both as a monotherapy and in combination with the GLP-1 receptor agonist semaglutide, and most of its later development has concentrated on the combination. The trial doses below are reported because they are part of the published record, not as guidance of any kind.

Phase 1b with semaglutide (Enebo et al., The Lancet, 2021) was a randomised, placebo-controlled, multiple-ascending-dose study at a single site in the United States. Ninety-six adults with a body-mass index of 27.0 to 39.9 kg/m² were randomised to once-weekly cagrilintide at 0.16, 0.30, 0.60, 1.2, 2.4 or 4.5 mg, or placebo, each co-administered with semaglutide 2.4 mg, for 20 weeks. Mean weight change at week 20 was −15.7% at 1.2 mg, −17.1% at 2.4 mg and −15.4% at 4.5 mg of cagrilintide, against −9.8% with pooled placebo plus semaglutide. Gastrointestinal events, mostly nausea, were the commonest adverse events; the paper also reports the pharmacokinetic half-life of cagrilintide at 159 to 195 hours [5].

Phase 2 monotherapy (Lau et al., The Lancet, 2021) was a multicentre, randomised, double-blind, placebo- and active-controlled dose-finding trial at 57 sites in ten countries. It enrolled 706 adults with overweight or obesity and no diabetes, randomised to once-weekly cagrilintide at 0.3, 0.6, 1.2, 2.4 or 4.5 mg, once-daily liraglutide 3.0 mg, or placebo, for 26 weeks. Mean weight change from baseline was −6.0%, −6.8%, −9.1%, −9.7% and −10.8% across the five cagrilintide doses, against −9.0% with liraglutide and −3.0% with placebo; all cagrilintide doses were superior to placebo. Gastrointestinal events occurred in 41 to 63% of cagrilintide participants against 32% on placebo, and injection-site reactions were dose-dependent. Anti-cagrilintide antibodies were detected in 46 to 73% of participants by week 26 without an apparent effect on weight change [6].

Phase 2 in type 2 diabetes (Frias et al., The Lancet, 2023) randomised 92 adults with type 2 diabetes and a body-mass index of at least 27 kg/m² on metformin to co-administered cagrilintide 2.4 mg with semaglutide 2.4 mg, semaglutide 2.4 mg alone, or cagrilintide 2.4 mg alone, once weekly for 32 weeks. HbA1c fell by 2.2 percentage points with the combination, 1.8 with semaglutide and 0.9 with cagrilintide. Body weight fell by 15.6% with the combination against 5.1% with semaglutide and 8.1% with cagrilintide, a difference that was significant against both comparators. Adverse events were predominantly gastrointestinal and mild or moderate [7].

REDEFINE 1 (Garvey et al., New England Journal of Medicine, 2025) is the first phase 3a trial. It enrolled 3,417 adults with obesity, or overweight with at least one complication, without diabetes, randomised 21:3:3:7 to cagrilintide–semaglutide 2.4 mg/2.4 mg, semaglutide 2.4 mg, cagrilintide 2.4 mg or placebo for 68 weeks. Under the treatment-policy estimand mean body-weight change was −20.4% with the combination, −14.9% with semaglutide alone, −11.5% with cagrilintide alone and −3.0% with placebo. Gastrointestinal adverse events were reported by 79.6% of combination recipients against 39.9% on placebo, and 5.9% discontinued because of adverse events [8].

REDEFINE 2 (Davies et al., New England Journal of Medicine, 2025) randomised 1,206 adults with type 2 diabetes and a body-mass index of at least 27 kg/m² to the combination or placebo for 68 weeks, and reported mean weight change of −13.7% against −3.4% [9].

REDEFINE 4, an open-label head-to-head trial against tirzepatide 15 mg in 809 adults with obesity over 84 weeks, was reported by the sponsor in February 2026. CagriSema produced 20.2% weight loss against 23.6% for tirzepatide under the treatment-regimen estimand, and did not meet its primary endpoint of non-inferiority. At the time of writing the full results have not appeared in a peer-reviewed journal. The same announcement states that a submission for the combination was made to the US Food and Drug Administration in December 2025 on the basis of REDEFINE 1 and 2, and that REDEFINE 3, a cardiovascular outcomes trial, is ongoing [10]. The status of this programme should be checked against the primary literature rather than taken from this page.

For the laboratory reader, the record shows that the monotherapy effect of cagrilintide is consistently smaller than that of the combination, and that the mechanistic basis of its additivity with GLP-1 receptor agonism is not settled.

Regulatory status in the United Kingdom

Cagrilintide is an investigational compound. It has no marketing authorisation from the MHRA, the European Medicines Agency or the US Food and Drug Administration, and no medicine containing it is available on prescription in the United Kingdom. BuyUK Peptides does not supply any medicinal product, and the research-grade peptide sold here is not a medicine, is not manufactured or presented as one, and carries no therapeutic claim.

Research-grade cagrilintide is supplied as a chemical for in-vitro laboratory use under the Terms of Sale. It is not for human or veterinary administration. Purchasers must be 18 or over and are responsible for ensuring their use of the material complies with the laws and institutional rules that apply to them. Our guide to the UK rules on research compounds sets this out in more detail.

Handling, storage and stability

Cagrilintide is supplied lyophilised, sealed under nitrogen in a glass vial with a rubber stopper and an aluminium flip-off crimp, in 5 mg and 10 mg quantities. In that state it is stable for extended periods when kept cold and dark. Because it is an amylin analogue, even one engineered against fibrillation, it deserves more care in solution than a typical GLP-1-class peptide.

Sealed vial. Store at 2–8 °C for routine use. For storage beyond a few months, −20 °C or below is preferable. Protect from light. Avoid repeated freeze–thaw cycles; take the vial out once and keep it at the working temperature from then on. Allow a refrigerated vial to reach room temperature before opening, so that moisture does not condense onto the cake.

Reconstitution. For most in-vitro work the compound is reconstituted in sterile water for injection, bacteriostatic water, or a buffer appropriate to the assay. Add the solvent slowly down the side of the vial rather than onto the cake, and swirl gently; do not shake and do not vortex. Agitation and air–water interfaces promote nucleation of aggregates in amylin-family peptides, and once fibrils have formed they do not redissolve. Foaming is a sign that the solution is being handled too vigorously. A minute or two of gentle swirling is normal for a lipidated peptide of this size. The reconstitution calculator gives the volume to add for a target concentration.

Reconstituted solution. Keep at 2–8 °C, protect from light, and use promptly. Prepare only the volume needed for the work in hand rather than storing solutions for weeks. If a solution must be held, keep it cold and dark in a low-binding container, inspect it before each use, and discard it if it becomes cloudy, viscous or shows particles, since any of these indicates aggregation. Do not freeze reconstituted solutions unless the buffer has been validated for that; freezing concentrates the peptide in the unfrozen fraction and is a common trigger for aggregation.

Solubility and filtration. Cagrilintide is soluble in water at the concentrations used in research. Acidic conditions and high concentrations both encourage self-association. Where a solution must be sterile-filtered, use a low-binding membrane (PES or PVDF rather than nylon or cellulose), because the lipid chain adsorbs to some filter materials and a measurable fraction of a dilute solution can be lost in the filter. Low-binding tips and tubes are advisable for the same reason.

What a sound certificate for cagrilintide looks like

Every batch we release carries an independent certificate of analysis, and the figures from it are transcribed on the product page and in the certificate register. For cagrilintide, a certificate should contain the following, and a reader should be able to check each item against this monograph.

Purity by RP-HPLC. Reversed-phase HPLC on a C18 column with UV detection, usually at 214 or 220 nm, reports purity as the area of the main peak as a percentage of all integrated peaks. A good batch of cagrilintide shows a single dominant peak with purity of 98% or above. Reduced or mis-paired disulfide forms typically elute close to the main peak; deamidation at one of the several asparagine residues and oxidation are the other common impurities. A broad, late-eluting hump rather than discrete peaks suggests aggregated material and should prompt questions about how the sample was prepared.

Identity by LC-MS. Electrospray mass spectrometry confirms that the main peak has the expected mass. For cagrilintide the average molecular weight is 4409.1 Da. Electrospray produces multiply charged ions, so a certificate may report the deconvoluted mass, the most abundant charge state, or both. The observed mass should agree with the theoretical value to within a few tenths of a dalton for a deconvoluted result; a mass two daltons higher than expected suggests the disulfide is reduced.

Net peptide content. Lyophilised peptides contain bound water and counter-ions, typically trifluoroacetate or acetate from purification, so the mass of powder in the vial is more than the mass of peptide. Net peptide content, where reported, expresses the fraction that is actual peptide, and it matters for preparing solutions of accurate concentration.

Endotoxin. Where the batch has been tested, a limulus amoebocyte lysate (LAL) result is reported in endotoxin units per milligram. This is relevant to cell-based assays, where endotoxin contamination can confound results.

Our guide to reading a certificate of analysis goes through a complete report line by line.

Related compounds

Cagrilintide is the only amylin analogue in our catalogue, and it is most often studied alongside the incretin-receptor peptides with which it has been combined or compared in the clinic. Semaglutide is the selective GLP-1 receptor agonist with which it is co-administered in CagriSema. Tirzepatide, a GIP and GLP-1 receptor co-agonist, is the comparator in REDEFINE 4. Retatrutide adds glucagon receptor agonism to make a triple agonist, the alternative strategy of combining signals within one molecule rather than co-administering two. The differences between them, and where an amylin analogue sits in relation to the incretin family, are the subject of our GLP-1 family comparison.

Frequently asked questions

Is cagrilintide a licensed medicine? No. It is an investigational compound with no marketing authorisation in the UK or anywhere else. The research material sold here is a lyophilised chemical for in-vitro use and is not for human or veterinary administration.

Is this the same as CagriSema? No. CagriSema is the sponsor's name for the investigational fixed combination of cagrilintide and semaglutide. The material described on this page is cagrilintide alone.

Why does the certificate quote a different mass from the formula weight? Electrospray results are often reported as a monoisotopic mass or a particular charge state rather than the average molecular weight. Both are valid; the certificate should say which it is reporting.

Why is the handling guidance stricter than for semaglutide or tirzepatide? Amylin is one of the most aggregation-prone peptides in human physiology. The design substitutions make cagrilintide far more stable than the native hormone, but the sensible assumption is that it will aggregate under conditions a GLP-1-class peptide would tolerate, so solutions are prepared gently, kept cold and used promptly.

How long does a sealed vial last? Lyophilised peptides of this class are stable for years at −20 °C and for many months at 2–8 °C. The batch certificate reports the test date; the storage guidance on this page applies from receipt.

References

1. Kruse T, Hansen JL, Dahl K, et al. Development of cagrilintide, a long-acting amylin analogue. Journal of Medicinal Chemistry. 2021;64(15):11183–11194. doi:10.1021/acs.jmedchem.1c00565. PMID 34288673.
2. Hay DL, Chen S, Lutz TA, Parkes DG, Roth JD. Amylin: pharmacology, physiology, and clinical potential. Pharmacological Reviews. 2015;67(3):564–600. doi:10.1124/pr.115.010629.
3. Christopoulos G, Perry KJ, Morfis M, et al. Multiple amylin receptors arise from receptor activity-modifying protein interaction with the calcitonin receptor gene product. Molecular Pharmacology. 1999;56(1):235–242. doi:10.1124/mol.56.1.235.
4. Cao J, Belousoff MJ, Johnson RM, et al. Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors. Nature Communications. 2025;16:3389. doi:10.1038/s41467-025-58680-y.
5. 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;397(10286):1736–1748. doi:10.1016/S0140-6736(21)00845-X. PMID 33894838.
6. 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;398(10317):2160–2172. doi:10.1016/S0140-6736(21)01751-7. PMID 34798060.
7. 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. The Lancet. 2023;402(10403):720–730. doi:10.1016/S0140-6736(23)01163-7. PMID 37364590.
8. Garvey WT, Blüher M, Osorto Contreras CK, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1). New England Journal of Medicine. 2025;393(7):635–647. doi:10.1056/NEJMoa2502081. PMID 40544433.
9. Davies MJ, Bajaj HS, Broholm C, et al. Cagrilintide–semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2). New England Journal of Medicine. 2025;393(7):648–659. doi:10.1056/NEJMoa2502082. PMID 40544432.
10. Novo Nordisk A/S. Company announcement: CagriSema REDEFINE 4 head-to-head trial results versus tirzepatide. Form 6-K filed with the US Securities and Exchange Commission, 23 February 2026. sec.gov filing.

This monograph summarises the published literature for laboratory researchers. It is not medical advice, and nothing on this site is for human or veterinary use.