B tier · viable
Cagrilintide has genuine randomised human efficacy data at phase 2 and large phase 3 exposure inside the CagriSema combination, but it is not approved as a standalone product anywhere and its solo phase 3 dataset is thin.
cagrilintide
Cagrilintide is a lipidated, long-acting analogue of the pancreatic hormone amylin that reduced body weight relative to placebo in a 706-participant randomised phase 2 trial. Its later development has been almost entirely as the amylin component of the fixed-dose CagriSema combination rather than as a monotherapy, so standalone long-term data remain limited.
the explanation
Amylin is a hormone your pancreas releases with insulin that helps tell your brain you are full; cagrilintide is a lab-made version engineered to last about a week per injection. In a mid-stage trial it produced more weight loss than placebo, but the company has mostly pursued it packaged together with semaglutide rather than on its own.
regulatory status
Investigational; not approved as a standalone drug
Cagrilintide has no marketing authorisation anywhere as a monotherapy. Novo Nordisk submitted a New Drug Application to FDA on 18 December 2025 for CagriSema (cagrilintide 2.4 mg plus semaglutide 2.4 mg) as a fixed-dose combination; as of this writing that application is under review and not approved. Material sold as research-grade cagrilintide is unapproved and outside any regulated supply chain.
how it works · proposed mechanism
Cagrilintide is designed to reproduce and prolong amylin's satiation signalling while resisting the aggregation and short duration that limited native human amylin.
Amylin receptor agonism
Amylin receptors are calcitonin receptor complexes paired with RAMP1, RAMP2 or RAMP3 accessory proteins. Cagrilintide activates these complexes non-selectively and also retains calcitonin receptor activity, which distinguishes it pharmacologically from the selective analogue pramlintide.
Hindbrain satiation signalling
Preclinical work localises amylin's anorectic effect largely to the area postrema and nucleus tractus solitarius, with downstream hypothalamic relay. This is a satiation pathway distinct from GLP-1 receptor signalling, which is the stated rationale for combining the two.
Lipidation for weekly exposure
A C20 diacid side chain attached through a gamma-glutamate linker promotes reversible albumin binding, slowing renal clearance. The same engineering strategy underlies semaglutide's weekly profile.
what’s reported
evidence shape
6 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
Almost every headline number attached to cagrilintide in consumer discussion actually comes from the CagriSema combination, not from cagrilintide alone; the standalone evidence peaks at a single 26-week phase 2 trial. Nothing sold as research-grade cagrilintide has been through the identity, purity or endotoxin testing that produced those trial results.
key published findings
- Human trial (randomised phase 2, Lau et al., Lancet 2021): 706 participants randomised to cagrilintide, 99 to liraglutide 3.0 mg and 101 to placebo; at 26 weeks mean weight change was -10.8% at the 4.5 mg dose versus -3.0% for placebo and -9.0% for liraglutide 3.0 mg.
- Human trial (phase 2 safety, same report): gastrointestinal adverse events occurred in 41-63% of cagrilintide participants versus 32% on placebo, alongside administration-site reactions.
- Human trial (randomised phase 3, REDEFINE 1, published NEJM 2025): the CagriSema fixed-dose combination produced a 22.7% mean weight reduction at 68 weeks, below the 25% target the sponsor had guided toward.
- Regulatory (FDA): NDA for CagriSema filed 18 December 2025; no standalone cagrilintide application exists.
- Preclinical/mechanistic: cagrilintide behaves as a non-selective amylin and calcitonin receptor agonist, which is the pharmacological basis for its longer action and broader receptor coverage than pramlintide.
limitations of the evidence
- The pivotal standalone dataset is a single 26-week dose-finding phase 2 trial; there is no long-duration monotherapy phase 3 outcome trial.
- Phase 3 data confound cagrilintide with semaglutide, so the incremental contribution of the amylin component over a GLP-1 agonist alone is inferred rather than directly isolated in a large trial.
- No cardiovascular or other hard-outcome trial has read out for cagrilintide in any form.
documented safety signals
- Dose-dependent gastrointestinal adverse events (nausea, constipation, diarrhoea) reported in 41-63% of phase 2 participants versus 32% on placebo.
- Injection- and administration-site reactions reported across trials.
- Amylin analogues as a class carry hypoglycaemia risk when used alongside insulin; pramlintide's US label carries a boxed warning on severe hypoglycaemia, and this class concern has not been excluded for cagrilintide.
- Grey-market vials carry unverified identity, purity, sterility and endotoxin status independent of any drug-class risk.
identity
| full name | Cagrilintide (AM833) |
| category | Metabolic |
| modality | peptide |
| formula | C194H312N54O59S2 |
| molar mass | 4409.01 g/mol |
| cas | 1415456-99-3 |
| half-life | Long enough to support once-weekly subcutaneous dosing in all published trials; a specific terminal half-life value could not be confirmed against a primary source and is left unstated here |
| sequence | Ac-KCNTATCATQRLAEFLRHSSNNFGPILPPTNVGSNTP-NH2 backbone with a Cys3-Cys8 disulfide bridge and an eicosanedioic acid-gamma-Glu lipid side chain at Lys1 (vendor characterisation data) |
laboratory handling
| storage | Vendor reference material is supplied lyophilised and specified for storage at -20C (about one year) or -80C (about two years), sealed, protected from light and moisture; reconstituted solution stability is markedly shorter (roughly one month at -20C, six months at -80C, per supplier data sheets). |
| solubility | Reported soluble in water to approximately 100 mg/mL (about 22.7 mM) with sonication in supplier characterisation data. |
| co-studied with | The only combination with substantial human evidence is cagrilintide plus semaglutide 2.4 mg as the fixed-dose CagriSema product studied in the REDEFINE phase 3 programme. That evidence applies to a specific manufactured fixed-ratio formulation studied under trial monitoring, and does not transfer to ad hoc pairings of separately sourced vials. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
6 citedDrugs.com regulatory tracker · 2026 · official
Cardiology in Review · 2023 · review
The Lancet · 2021 · randomized
The Lancet · 2021 · randomized
Novo Nordisk company release (reporting NEJM publication) · 2025 · randomized
MedChemExpress technical documentation · 2024 · preclinical
others in Metabolic