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Cagrilintide

Cagrilintide Reconstitution Calculator

Cagrilintide (AM833, NNC0174-0833) is a long-acting analogue of amylin, the pancreatic hormone co-secreted with insulin that induces satiety. It is not a GLP-1 receptor agonist and has no incretin activity of its own: it acts at amylin and calcitonin receptors, slowing gastric emptying and suppressing glucagon. Native amylin cannot be used as a drug because it aggregates into amyloid fibrils, so cagrilintide is a stabilised, lipidated version engineered for once-weekly subcutaneous injection. It is investigational everywhere, and most of its human data comes from co-administration with semaglutide as CagriSema.

01Inputs
03Evidence

What the evidence says

Cited human dosesRandomised trials

The published trials that established Cagrilintide dosing are reported below, each with the paper it comes from. The structured range table — every range with its experience level, frequency and linked citation — lives in the Dosavy compound library.

04Facts

Cagrilintide at a glance

Category
GLP-1
Half-life
Not established
Routes
Subcutaneous
Regulatory status
Not approved
Also sold as
AM833, NNC0174-0833, long-acting amylin analogue, amylin receptor agonist, CagriSema component

Mechanism

A long-acting analogue of amylin — the pancreatic hormone co-secreted with insulin that induces satiety. It is NOT a GLP-1 receptor agonist and has no incretin activity of its own; it acts at amylin and calcitonin receptors, slowing gastric emptying, suppressing glucagon and reducing food intake through a satiety pathway distinct from GLP-1. Native amylin is unusable as a drug because it aggregates into amyloid fibrils, and the approved short-acting analogue pramlintide needs three daily injections; cagrilintide is a stabilised, lipidated analogue engineered for once-weekly subcutaneous dosing. Its clinical development is dominated by co-administration with semaglutide (CagriSema), where the two satiety mechanisms are additive.

Reconstitution

There is no approved presentation and no published reconstitution instruction — trial participants self-injected a ready-prepared solution. Any lyophilised powder sold as 'cagrilintide' has unverified identity, purity and peptide content, so the milligram figures from the trials below cannot be assumed to describe what is in such a vial. Amylin analogues in particular are prone to fibril aggregation, which is a formulation problem, not something a home reconstitution can inspect for.

Storage

No approved product and therefore no manufacturer storage instructions exist. Trial material was a solution for subcutaneous self-injection supplied under sponsor-controlled conditions; nothing in this packet establishes stability conditions for material obtained outside a trial.

Frequency in practice

Once weekly by subcutaneous injection in every published trial, after a multi-week dose-escalation period.

Regulatory

Investigational. Cagrilintide (Novo Nordisk) is not approved by the FDA, the EMA or Swissmedic, either as monotherapy or as part of the CagriSema fixed-dose combination with semaglutide. Development is furthest advanced for CagriSema (phase 3 REDEFINE and REIMAGINE programmes); cagrilintide monotherapy has completed a phase 2 dose-finding trial and has been carried as a comparator arm at 2.4 mg into phase 3.

05Warnings

What to know before anything else

  • Not approved for human use anywhere, as monotherapy or in combination. There is no prescribing information, so there is no boxed warning, no contraindication list, no drug-interaction table and no approved maximum dose — the doses below are trial protocol doses, not a licensed regimen.

  • Material sold as 'cagrilintide' outside a clinical trial is not the trial drug. Identity, purity, peptide content and sterility are unverified.

  • Gastrointestinal adverse events — nausea and vomiting in particular — are the dominant adverse effect in every published trial, and the trials used multi-week dose escalation specifically to manage them.

  • Amylin analogues slow gastric emptying and suppress glucagon. Pramlintide, the only amylin analogue approved in the US, carries a boxed warning for severe insulin-induced hypoglycaemia when used with insulin. No regulator has assessed whether that risk applies to cagrilintide, so anyone using insulin or an insulin secretagogue is in genuinely uncharacterised territory.

  • Most of the human safety data for cagrilintide comes from trials where it was co-administered with semaglutide 2.4 mg, so adverse effects attributable to cagrilintide alone are less well separated than the volume of trial data suggests.

  • Two published findings are reassuring but narrow: a thorough QT study found no clinically relevant QTc prolongation in healthy participants, and single-dose studies found renal or hepatic impairment did not meaningfully change pharmacokinetics. Neither speaks to long-term safety.

  • No published pregnancy, lactation or paediatric data. A paediatric phase 3 trial is only now recruiting.

06Questions

Cagrilintide questions

Is cagrilintide approved anywhere?

No. Cagrilintide (Novo Nordisk) is not approved by the FDA, the EMA or Swissmedic, either as monotherapy or as part of the CagriSema fixed-dose combination with semaglutide. Because there is no prescribing information, there is no boxed warning, no contraindication list, no drug-interaction table and no approved maximum dose. Development is furthest advanced for CagriSema in the phase 3 REDEFINE and REIMAGINE programmes; monotherapy has completed a phase 2 dose-finding trial and been carried into phase 3 as a comparator arm.

What doses have actually been given to people in trials?

The phase 2 dose-finding trial published in the Lancet in 2021 (PMID 34798060) randomised adults with overweight or obesity to once-weekly subcutaneous cagrilintide at 0.3, 0.6, 1.2, 2.4 or 4.5 mg, against once-daily liraglutide 3.0 mg and placebo, over 26 weeks including a dose-escalation period of up to six weeks. The programme then settled on 2.4 mg once weekly: that is the monotherapy arm carried into the 68-week phase 3 REDEFINE 1 trial (PMID 40544433), where 302 participants received it. These are trial protocol doses, reached by stepwise escalation, not a licensed regimen.

How does cagrilintide differ from a GLP-1 agonist like semaglutide?

Different receptor family. Semaglutide is an incretin mimetic acting at the GLP-1 receptor; cagrilintide acts at amylin and calcitonin receptors and has no incretin activity. Both reduce food intake and slow gastric emptying, which is why the gastrointestinal effects add up, but the satiety pathways are distinct rather than duplicated. That non-overlap is the whole rationale for combining them as CagriSema, and it is why pairing two GLP-1 agonists was never pursued the same way.

What is CagriSema, and was the combination studied or improvised?

It is cagrilintide co-administered with semaglutide, and it is a studied regimen. The phase 1b trial in the Lancet (PMID 33894838) escalated cagrilintide from 0.16 up to 4.5 mg alongside semaglutide 2.4 mg in six sequential cohorts of 96 participants, stepping both drugs together at four-week intervals over 16 weeks rather than adding them abruptly. The phase 3a REDEFINE 1 trial (PMID 40544433, 3,417 participants) then compared cagrilintide 2.4 mg plus semaglutide 2.4 mg against each agent alone and placebo over 68 weeks. The co-titration is part of the design, not an optional detail.

What are the main safety concerns?

Gastrointestinal adverse events, nausea and vomiting in particular, are the dominant adverse effect in every published trial, which is why the trials used multi-week escalation. Pramlintide, the only amylin analogue approved in the US, carries a boxed warning for severe insulin-induced hypoglycaemia when combined with insulin; no regulator has assessed whether that risk carries over to cagrilintide, so anyone using insulin or an insulin secretagogue is in uncharacterised territory. Two published findings are reassuring but narrow: a thorough QT study found no clinically relevant QTc prolongation in healthy participants, and single-dose studies found renal or hepatic impairment did not meaningfully change pharmacokinetics. Neither speaks to long-term safety, and there are no published pregnancy, lactation or paediatric data.

Is there stability or storage guidance for cagrilintide?

None that comes from a manufacturer. No approved product exists, so no approved storage instructions exist either. Trial material was a ready-prepared solution for subcutaneous self-injection supplied under sponsor-controlled conditions, and nothing in the published record establishes stability conditions for material obtained outside a trial. Storage claims printed on a research-peptide vial, including the expiry date, are unverified.

Do the trial milligram figures describe a vial bought outside a trial?

No, and this is the specific reason the numbers do not transfer. There is no approved presentation and no published reconstitution instruction, because trial participants injected a ready-made solution rather than mixing a powder. Any lyophilised material sold as cagrilintide has unverified identity, purity and peptide content, so a trial dose in milligrams cannot be assumed to describe what is in such a vial. Amylin analogues are also prone to fibril aggregation, which is a formulation problem that no home reconstitution can inspect for. The calculator above converts vial size and mixing volume into mg/ml and syringe units; it says nothing about what the vial contains.

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