Cagrilintide — identity, handling and published literature

Cagrilintide is a lipidated, long-acting synthetic analogue of human amylin, supplied as a sterile lyophilised powder for reconstitution in the laboratory.

Presentation and physical properties

Cagrilintide is presented as a white to off-white lyophilised powder in a sealed glass vial, produced by solid-phase peptide synthesis and purified chromatographically. It is a large acylated peptide of nominal average molecular mass 4409 g/mol, substantially heavier than the small-peptide fragments commonly held in the same freezer.

The parent molecule, human amylin (islet amyloid polypeptide), is notoriously prone to forming amyloid fibrils in solution, and this property is the central problem the cagrilintide medicinal chemistry programme set out to engineer around [1]. The published development work describes substitutions intended to lower beta-sheet propensity and stabilise the peptide, together with a fatty diacid side chain that confers reversible albumin binding and extends circulating half-life [1]. The practical consequence for handling is that the lyophilised solid is comparatively stable, while any aqueous solution should be treated as a peptide preparation with a finite working life.

The lyophilised cake occupies a small fraction of the vial volume and is easily disturbed. Vials should be inspected before reconstitution: a cake that has collapsed, discoloured or shifted may indicate a breach of the vacuum seal or a temperature excursion in transit.

Reconstitution arithmetic

Reconstitution is a dilution calculation and nothing more. The mass in the vial is fixed; the concentration is set entirely by the volume of diluent introduced. The relationship is:

concentration (mg/mL) = mass in vial (mg) ÷ diluent volume (mL)

For a 5 mg vial, the following concentrations result. The right-hand columns express the same figures per unit of graduation on a U-100 insulin syringe, where one unit corresponds to 0.01 mL, because that is the graduation most laboratory syringes carry.

The 3 mL figure does not divide evenly and is shown rounded; the exact value is 5 ÷ 3 = 1.6667 mg/mL. Where a calculation is carried forward, the unrounded value should be used and rounding applied only at the final step.

Two points of arithmetic hygiene apply to any lyophilised peptide. First, the diluent volume is not identical to the final solution volume — the dissolved solid contributes its own displacement — but at these masses the difference is well below the resolution of a 1 mL syringe and is conventionally disregarded. Second, the figures above assume the full nominal mass is present and fully dissolved; an incompletely dissolved cake yields a lower concentration than the arithmetic predicts, and the error is invisible.

Diluent should be directed against the vial wall rather than onto the cake, and the vial swirled or left to stand rather than shaken. This document states the mass-to-volume relationship only. It does not state, and should not be read as stating, any target amount for any purpose.

Storage and stability

The lyophilised solid is stored refrigerated at 2–8 °C for routine holding, or at −20 °C for extended storage, protected from light and from moisture. Vials should be allowed to equilibrate to room temperature before the seal is broken, so that atmospheric moisture does not condense onto cold contents when the vacuum is released.

Once reconstituted, the solution is held at 2–8 °C. The choice of diluent governs how the vial may be used: bacteriostatic water contains benzyl alcohol as a preservative and permits repeated withdrawals from the same vial, whereas sterile water contains no preservative and is appropriate only where the vial is used once. Neither diluent alters the arithmetic above.

Repeated freeze–thaw cycling of reconstituted material should be avoided. Aggregation at the air–liquid interface is a general failure mode for peptides in solution and is the reason vigorous agitation is discouraged; in the case of an amylin analogue it is of particular interest, given that fibrillation of the parent peptide was the specific liability addressed during development [1].

No published stability dataset for reconstituted cagrilintide outside the manufacturer’s own investigational presentation was located. Working assumptions about in-use life should therefore be treated as extrapolation from general peptide practice rather than as a measured property of this compound.

Analytical identity

Cagrilintide is registered under CAS number 1415456-99-3 and carries the UNII code AO43BIF1U8. PubChem records it as CID 171397054, with molecular formula C₁₉₄H₃₁₂N₅₄O₅₉S₂, average molecular weight 4409 g/mol and monoisotopic mass 4406.2515. It holds an International Nonproprietary Name and appears in the development literature under the codes AM833 and NN0174-0833, and as “analogue 23” in the medicinal chemistry paper describing its selection [1].

Structurally it is an acylated analogue of human amylin. The two sulphur atoms in the formula correspond to an intramolecular cysteine–cysteine disulphide bridge, which is present in the deposited structural records and in the PubChem stereochemical description. The Protein Data Bank entry 7BG0 deposits the AM833 backbone as a maltose-binding-protein fusion, annotated as human islet amyloid polypeptide carrying seven mutations — amylin being a 37-residue peptide. The full substitution pattern and the composition of the fatty diacid side chain are specified in the primary development paper [1]; they are not restated here, because no primary source giving the complete modified sequence as an unambiguous single-letter string was resolved.

Routine identity and purity assessment for a peptide of this class rests on reversed-phase HPLC for chromatographic purity, electrospray mass spectrometry for molecular mass confirmation, and amino acid analysis or peptide mapping for sequence corroboration. The observed mass should be checked against the acylated, disulphide-bridged species rather than against a linear unmodified amylin backbone, since both the diacid and the disulphide shift the expected value.

Cryo-electron microscopy structures of cagrilintide bound to the calcitonin receptor and to amylin receptors AMY₁R, AMY₂R and AMY₃R have been published, giving a structural reference for the bound conformation [3].

What the published literature investigated

In vitro and structural pharmacology

The compound’s development was reported in 2021, describing the design rationale, the structure–activity work behind the substitutions and the lipidation, and the selection of the clinical candidate [1]. A separate pharmacological characterisation profiled AM833 across 25 endpoints in HEK293 cells expressing calcitonin-family receptors, comparing it against six selective and non-selective agonists including pramlintide and salmon calcitonin; the authors reported that AM833 showed a distinct profile across measures of receptor binding, activation and regulation [2].

A 2025 cryo-electron microscopy study resolved cagrilintide in complex with Gs-coupled calcitonin and amylin receptors. The authors reported an amylin-like binding mode but distinct conformational dynamics at these receptors relative to the comparator peptides examined [3].

A 2026 analytical study characterised the in vitro metabolic profile of three amylin receptor agonists — pramlintide, cagrilintide and KBP-066 — using human skin S9 fraction, kidney S9 fraction and biological fluids, in the context of preventive doping research. All three compounds degraded to stable products the authors judged suitable as detection targets, and the in vitro findings were checked against post-administration rat plasma samples [16].

Rodent and cross-species work

A 2025 study in wild-type and RAMP1/3 knockout mice maintained on a high-fat diet reported that the body-weight effect of cagrilintide was impaired in the absence of RAMP1/3, and concluded that the effect observed in that model depends on amylin receptors 1 and 3 [4].

A 2026 study assembled a cross-species transcriptomic atlas of the dorsal vagal complex spanning rat, mouse, macaque and human tissue, covering more than 530,000 cells across 80 neuronal populations. Using spatial profiling, chemogenetic activation and knockdown of prolactin-releasing hormone expression, the authors identified conserved neuronal populations they reported as mediating the energy-balance effects of cagrilintide in the animal models studied; the human component was comparative gene-expression analysis rather than intervention [5].

Human trials — cagrilintide alone

A phase 2 dose-finding trial published in 2021 randomised 706 adults without diabetes across 57 sites in 10 countries, comparing five weekly cagrilintide dose levels (0.3 to 4.5 mg) against placebo and against an active comparator over a 26-week treatment period. The investigators reported body-weight reductions of 6.0% to 10.8% across the cagrilintide groups against 3.0% with placebo, with gastrointestinal disorders the most frequently reported adverse events [7].

A cagrilintide monotherapy arm was also included in the 2023 phase 2 trial in type 2 diabetes [8] and, at larger scale, in the phase 3 REIMAGINE 2 trial, which contained a 152-participant cagrilintide-alone group [12].

Human trials — cagrilintide with semaglutide

This is where the great majority of the human evidence sits, and it is a large and recent body of work.

A phase 1b multiple-ascending-dose trial published in 2021 exposed 95 participants across six sequential cohorts to weekly cagrilintide (0.16–4.5 mg) or placebo alongside semaglutide 2.4 mg, over a 16-week escalation, 4-week maintenance and 5-week follow-up. The authors reported adverse events that were mild to moderate in severity and greater weight reduction at higher cagrilintide dose levels than with placebo [6].

A phase 2 trial published in 2023 enrolled 92 adults with type 2 diabetes across 17 US sites for 32 weeks, comparing the combination against each agent alone. Reported reductions in glycated haemoglobin were 2.2, 1.8 and 0.9 percentage points for the combination, semaglutide alone and cagrilintide alone respectively, with body-weight reductions of 15.6%, 5.1% and 8.1%; no severe hypoglycaemia was reported [8].

Two phase 3a trials were published together in 2025. REDEFINE 1 randomised 3,417 adults with overweight or obesity for 68 weeks and reported mean body-weight change of −20.4% with the combination against −3.0% with placebo, with gastrointestinal adverse events in 79.6% of the treatment group against 39.9% on placebo, described as mainly transient and mild to moderate [9]. REDEFINE 2 randomised 1,206 adults with type 2 diabetes and body-mass index of 27 or above across 12 countries for 68 weeks, reporting mean body-weight change of −13.7% against −3.4% with placebo [10].

REDEFINE 5, published in 2026, randomised 331 participants across 21 sites in Japan and one in Taiwan for 68 weeks, comparing the combination against semaglutide alone, and reported mean body-weight change of −18.4% against −11.9% [11].

The REIMAGINE programme addressed type 2 diabetes. REIMAGINE 1 randomised 189 participants inadequately controlled on diet and exercise over 40 weeks [13]; REIMAGINE 2 randomised 2,713 participants over 68 weeks across six arms including monotherapy and placebo comparators, reporting a glycated haemoglobin reduction of 1.91 against 1.75 percentage points for semaglutide alone [12]; and REIMAGINE 3 randomised 274 participants as an add-on to basal insulin over 40 weeks, reporting a glycated haemoglobin reduction of 2.33 percentage points against 0.66 with placebo [14].

Pharmacokinetics in defined populations

A 2026 study reported two parallel single-dose investigations in participants stratified by renal function (33 adults) and hepatic function (32 adults). The authors reported no clinically relevant differences in cagrilintide pharmacokinetics across degrees of impairment [15].

Reviews

A 2024 narrative review in Cardiology in Review summarises the mechanism and the clinical development record to that date [17]. It is a secondary source and is listed for orientation rather than as evidence.

Evidence gaps and limitations

Cagrilintide holds no marketing authorisation in any jurisdiction. It follows that no regulator has completed a benefit–risk assessment and published an assessment report on it, and that every finding above stands on the sponsor’s own trial programme rather than on independent regulatory review of the underlying data.

The monotherapy evidence base is markedly thinner than the combination base. One phase 2 dose-finding trial of 706 participants [7], a 152-participant arm within REIMAGINE 2 [12] and a small arm within the 2023 phase 2 trial [8] constitute essentially the whole of it. There is no phase 3 trial of cagrilintide alone in the record consulted. Most of what is known about this molecule in humans is known about it in the presence of semaglutide, and the two cannot be disentangled from the combination results.

No published trial extends beyond 68 weeks. There is no reported cardiovascular or other long-term outcome trial for cagrilintide. No long-term immunogenicity or anti-drug-antibody dataset was located.

There is no pharmacopoeial monograph for cagrilintide in the British Pharmacopoeia, the European Pharmacopoeia or the United States Pharmacopeia. There is therefore no compendial identity, purity or impurity-limit standard against which any preparation of this substance can be assessed, and no official reference standard. Comparisons between preparations from different sources rest on whatever analytical methods each party chose to run.

Critically, the human safety and pharmacokinetic data summarised above were generated with investigational material manufactured under Good Manufacturing Practice to a defined specification and administered under clinical supervision. Those findings are properties of that material in that setting. They do not transfer to material of any other provenance, and nothing in the published record supports treating them as though they do.

No published stability data exist for reconstituted material held outside the manufacturer’s presentation, and no published data address the substance’s behaviour under the storage and handling conditions of a general laboratory.

Regulatory and standards position

United Kingdom. Cagrilintide has no marketing authorisation from the MHRA, alone or in combination. It is not a licensed medicine in the UK and is not available on prescription. Under the Human Medicines Regulations 2012, placing a product on the market for administration to human beings requires an authorisation. Under MHRA Guidance Note 8 and the doctrine of “medicinal product by presentation” — the position taken by the Court of Justice in Ter Voort (C-219/91) — it is the claim made for a substance, not the identity of the molecule, that determines whether it falls within medicines law. A substance supplied as a laboratory chemical becomes a medicinal product the moment it is presented as having properties for treating or preventing disease.

European Union. No EMA marketing authorisation exists. No marketing authorisation application for cagrilintide or the cagrilintide–semaglutide combination had been publicly confirmed in the sources consulted.

United States. Cagrilintide is not FDA-approved. A New Drug Application for the cagrilintide–semaglutide combination was submitted to the FDA on 18 December 2025, with a first review decision anticipated by the sponsor in late 2026. The FDA’s position is that cagrilintide is not a component of any approved drug and does not appear on the bulk drug substance lists that permit compounding under sections 503A and 503B of the Federal Food, Drug, and Cosmetic Act.

Controlled-drug status. Cagrilintide is not a controlled drug. It is not scheduled under the Misuse of Drugs Act 1971 or the Misuse of Drugs Regulations 2001, and it is not subject to the export and possession controls that apply to scheduled substances.

Anti-doping. Cagrilintide does not appear on the WADA Prohibited List in force for 2026, and amylin analogues are not listed as a class. The related GLP-1 receptor agonists are likewise not prohibited: semaglutide was placed on WADA’s Monitoring Program in 2024, and markers of tirzepatide were added to that programme with effect from 1 January 2026. The Monitoring Program is a data-gathering mechanism and carries no restriction on use. Anti-doping laboratories have nonetheless published metabolite characterisation and detection-method development for cagrilintide under the heading of preventive doping research [16], which is the work that would normally precede any listing decision. The Prohibited List is reissued annually and this position should be verified against the current edition rather than assumed to persist.

Enforcement history. Cagrilintide has been named directly in United States enforcement action against vendors. On 10 December 2024 the FDA issued a warning letter to Summit Research Peptides, one of four issued simultaneously, citing cagrilintide among the products offered on the vendor’s website alongside semaglutide, retatrutide, tirzepatide and mazdutide. The agency treated the products as unapproved new drugs introduced into interstate commerce contrary to sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act. The reasoning is the material point: the FDA held that a “research use only” designation on the product did not settle the question, because the vendor’s own marketing — including social media material promoting cagrilintide and semaglutide for weight reduction in people — established that the products were intended as drugs for human use. Further letters to peptide and GLP-1 vendors followed in 2025 and 2026. The consistent principle across UK and US law is that a research-use label is not a defence against the claims made around the product.

Laboratory handling and safety

Cagrilintide should be handled as a biologically active research chemical of unknown occupational toxicity. No occupational exposure limit has been established for it, and no substance-specific safety data are available beyond what a supplier’s safety data sheet states.

Standard practice applies: gloves, eye protection and a laboratory coat; handling of the dry powder in a manner that avoids generating dust, since the lyophilised solid is light and readily disturbed; and no eating, drinking or cosmetic application in the handling area. Hands should be washed after handling regardless of glove use.

Reconstitution should be carried out with aseptic technique and appropriate sharps handling. Needles and syringes go to a rigid sharps container; residual solution and used vials are disposed of as chemical or clinical waste according to local arrangements, not to drain and not to general refuse.

Vials should be labelled at reconstitution with the compound name, the resulting concentration, the diluent used and the date. Unlabelled reconstituted vials are a common source of error and the concentration cannot be recovered by inspection.

Material should be stored securely, out of reach of anyone not trained in its handling, and kept clearly segregated from anything intended for human or veterinary administration.

References

1. Kruse T, Hansen JL, Dahl K, Schäffer L, Sensfuss U, Poulsen C, Schlein M, Hansen AMK, Jeppesen CB, Dornonville de la Cour C, Clausen TR, Johansson E, Fulle S, Skyggebjerg RB, Raun K. Development of cagrilintide, a long-acting amylin analogue. Journal of Medicinal Chemistry. 2021;64(15):11183–11194. Model: in vitro / medicinal chemistry. PMID 34288673
2. Fletcher MM, Keov P, Truong TT, Mennen G, Hick CA, Zhao P, Furness SGB, Kruse T, Clausen TR, Wootten D, Sexton PM. AM833 is a novel agonist of calcitonin family G protein-coupled receptors: pharmacological comparison with six selective and nonselective agonists. The Journal of Pharmacology and Experimental Therapeutics. 2021;377(3):417–440. Model: in vitro (HEK293 cells expressing calcitonin-family receptors). PMID 33727283
3. Cao J, Belousoff MJ, Johnson RM, Keov P, Mariam Z, Deganutti G, Christopoulos G, Hick CA, Reedtz-Runge S, Glendorf T, Ballarin-Gonzalez B, Raun K, Bayly-Jones C, Wootten D, Sexton PM. Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors. Nature Communications. 2025;16:3389. Model: in vitro (cryo-electron microscopy of receptor complexes). PMID 40204768
4. Carvas AO, et al. Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3. EBioMedicine. 2025;118:105836. Model: rodent (wild-type and RAMP1/3 knockout mice on high-fat diet). PMID 40609154
5. Ludwig MQ, et al. A cross-species atlas of the dorsal vagal complex reveals neural mediators of the effects of cagrilintide on energy balance. Nature Metabolism. 2026;8(6):1350–1367. Model: rodent, with comparative rat, mouse, macaque and human tissue transcriptomics. PMID 42260119
6. Enebo LB, Berthelsen KK, Kankam M, Lund MT, Rubino DM, Satylganova A, Lau DCW. 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. Model: human trial (phase 1b, 95 participants exposed). PMID 33894838
7. Lau DCW, Erichsen L, Francisco AM, Satylganova A, le Roux CW, McGowan B, Pedersen SD, Pietiläinen KH, Rubino DM, Batterham RL. 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. Model: human trial (phase 2, 706 participants, 26 weeks). PMID 34798060
8. Frias JP, Deenadayalan S, Erichsen L, Knop FK, Lingvay I, Macura S, Mathieu C, Pedersen SD, Davies M. 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. Model: human trial (phase 2, 92 participants, 32 weeks). PMID 37364590
9. Garvey WT, et al. Coadministered cagrilintide and semaglutide in adults with overweight or obesity. The New England Journal of Medicine. 2025;393(7):635–647. Model: human trial (REDEFINE 1, phase 3a, 3,417 participants, 68 weeks). PMID 40544433
10. Davies MJ, et al. Cagrilintide–semaglutide in adults with overweight or obesity and type 2 diabetes. The New England Journal of Medicine. 2025;393(7):648–659. Model: human trial (REDEFINE 2, phase 3a, 1,206 participants, 68 weeks). PMID 40544432
11. Yamauchi T, et al. Efficacy and safety of co-administered cagrilintide and semaglutide versus semaglutide alone in adults with overweight or obesity with or without type 2 diabetes in Japan and Taiwan (REDEFINE 5): a multicentre, randomised, active-controlled, phase 3a trial. The Lancet Diabetes & Endocrinology. 2026;14(6):450–462. Model: human trial (phase 3a, 331 participants, 68 weeks). PMID 42009015
12. Buse JB, et al. Cagrilintide–semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study. The Lancet Diabetes & Endocrinology. 2026;14(8):662–677. Model: human trial (phase 3, 2,713 participants, 68 weeks, six arms). PMID 42251859
13. Aroda VR, et al. Efficacy and safety of once-weekly cagrilintide–semaglutide (CagriSema) in adults with type 2 diabetes inadequately controlled on diet and exercise (REIMAGINE 1): a randomised, double-blind, placebo-controlled, phase 3a study. The Lancet Diabetes & Endocrinology. 2026;14(8):649–661. Model: human trial (phase 3a, 189 participants, 40 weeks). PMID 42251860
14. Rosenstock J, et al. Cagrilintide–semaglutide (CagriSema) as an add-on to basal insulin in adults with type 2 diabetes (REIMAGINE 3): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. The Lancet. 2026;408(10549):38–51. Model: human trial (phase 3a, 274 participants, 40 weeks). PMID 42251856
15. Nielsen MJF, et al. Renal or hepatic impairment does not affect pharmacokinetics, safety, or tolerability of subcutaneous cagrilintide. Clinical Pharmacokinetics. 2026;65:1087–1099. Model: human trial (two single-dose pharmacokinetic studies, 33 and 32 participants). PMID 42228334
16. Alhalabi H, Borschel L, Le Foll C, Thomas A, Bally L, Thevis M. In vitro metabolic profiling of weight-loss-inducing amylin receptor agonists in the context of preventive doping research. Journal of Pharmaceutical and Biomedical Analysis. 2026;273:117418. Model: in vitro (human skin and kidney S9 fractions, biological fluids), with rat plasma corroboration. PMID 41702251
17. D’Ascanio AM, Mullally JA, Frishman WH. Cagrilintide: a long-acting amylin analog for the treatment of obesity. Cardiology in Review. 2024;32(1):83–90. Model: review. PMID 36883831

Research use only

Cagrilintide is supplied strictly as a laboratory chemical for in vitro research and analytical use. It is not a medicinal product and holds no marketing authorisation in the United Kingdom, the European Union, the United States or elsewhere.

It is not for human or veterinary use, not for administration to any person or animal, not for diagnostic use, and not for use as a food, cosmetic or household chemical. It must not be supplied or held for administration to human beings.

Nothing in this document is a recommendation to administer cagrilintide, a statement that it is safe or effective for any purpose, or guidance on any amount, route, schedule or protocol of use. The trial results reported above are statements about what published studies observed under investigational conditions with material of defined pharmaceutical provenance; they are not statements about this substance as supplied, and they are not claims made for it.

This entry is a technical and bibliographic record intended for qualified personnel working in an appropriately equipped and controlled laboratory environment.