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CagriSema

Also known as cagrilintide/semaglutide, cagrilintide-semaglutide

Fixed-dose combination of the amylin analogue cagrilintide with semaglutide; filed with the FDA, not approved.

clinically proven Metabolic & weight research chemical

At a glance

Category
Metabolic & weight
Status
research chemical
Route
subcutaneous, once weekly
Half-life
both components are engineered for once-weekly dosing; the pharmacokinetics are those of the two peptides given together, not of a new molecule
Onset
weight loss over months; in REDEFINE 1 the curve had not clearly plateaued at week 68 1
Sequence
Two separate peptides in one solution; see the cagrilintide and semaglutide entries for their sequences.

Not approved anywhere at the time of writing. Novo Nordisk submitted a New Drug Application to the FDA on 18 December 2025 for once-weekly CagriSema (cagrilintide 2.4 mg with semaglutide 2.4 mg) for weight management in adults with obesity, or overweight with at least one weight-related comorbid condition; the company's own announcement states that CagriSema is not approved in the US or the EU 4. A regulatory decision had not been announced as of July 2026. The submission rests on REDEFINE 1 and REDEFINE 2 12. One half of the combination is itself unapproved: the FDA states that cagrilintide cannot be used in compounding under federal law, is not a component of any FDA-approved drug, and has not been found safe and effective for any condition 7. Powders sold online as 'CagriSema', or as separate cagrilintide and semaglutide vials to be mixed, are not the registered product, are not made to its specification, and are not checked for identity, purity or sterility; the FDA has issued warning letters to firms selling GLP-1 compounds labelled 'for research purposes' or 'not for human consumption' while providing human dosing instructions 78.

Doping status: Prohibited (WADA S0, non-approved substances)

Checked against the WADA 2026 Prohibited List. For a specific product and country, Global DRO is the lookup athletes are expected to use — the List names substances, not brand names.

What is in it

Mechanism of action

CagriSema is not a new molecule. It is two established peptides supplied at a fixed ratio in a single weekly subcutaneous injection: cagrilintide 2.4 mg, a long-acting amylin analogue, and semaglutide 2.4 mg, a GLP-1 receptor agonist. Each has its own entry on this site, and the reason for reading them is that the safety and pharmacology of each component belong to that component. What belongs to the combination, and only to the combination, is the trial evidence below.

The rationale is that amylin and GLP-1 reduce food intake through different routes. Semaglutide acts at GLP-1 receptors in the hypothalamus and hindbrain, slows gastric emptying and suppresses glucagon. Cagrilintide acts at amylin and calcitonin receptors in the area postrema and related hindbrain nuclei, where amylin signalling contributes to meal termination and satiety. Adding a second, non-overlapping satiety signal is expected to produce more weight loss than either alone, and in REDEFINE 1 the combination did outperform each single agent given at the same dose 1.

The fixed ratio is the practical limitation. Cagrilintide and semaglutide cannot be titrated independently, so a person who tolerates one component poorly cannot reduce it without reducing the other. Both components are escalated together over sixteen weeks in the trials, and gastrointestinal adverse events were reported by roughly four in five participants receiving the combination in REDEFINE 1, against roughly two in five on placebo 1.

What the research shows

Among the compounds on this site that are not yet approved, CagriSema has the strongest evidence base: two completed phase 3a trials in a combined 4,623 randomised participants, both published in the New England Journal of Medicine 12. The weight effect is large. The complication is REDEFINE 4, an open-label head-to-head against tirzepatide 15 mg, which CagriSema lost: it did not meet its primary endpoint of non-inferiority 3. So the honest summary is a drug with very good absolute results that has not been shown to be at least as good as an approved competitor.

Research in humans

REDEFINE 1 (NEJM, 2025) randomised 3,417 adults with obesity, or overweight with a complication and without diabetes, to CagriSema, semaglutide 2.4 mg alone, cagrilintide 2.4 mg alone, or placebo for 68 weeks. Estimated mean weight change was -20.4% with CagriSema against -3.0% with placebo (difference -17.3 percentage points), and CagriSema was more likely than placebo to reach reductions of 5%, 20%, 25% and 30% or more 1. REDEFINE 2 (NEJM, 2025) randomised 1,206 adults with obesity and type 2 diabetes 3:1 to CagriSema or placebo for 68 weeks: -13.7% against -3.4%, with 73.5% of the CagriSema group reaching a glycated haemoglobin of 6.5% or below against 15.9% on placebo 2. A secondary analysis of REDEFINE 1 reported blood-pressure reduction 5. REDEFINE 5 compared co-administered cagrilintide and semaglutide against semaglutide alone in Japan and Taiwan 6. REDEFINE 4, announced by press release on 23 February 2026, was an 84-week open-label trial in 809 people comparing CagriSema against tirzepatide 15 mg; CagriSema produced 23.0% weight loss against 25.5% for tirzepatide on the efficacy estimand, and did not meet its primary endpoint of non-inferiority 3.

Animal and lab research

Not the relevant literature here. The animal work belongs to the individual components and is covered in their entries. There is no separate preclinical programme for the fixed combination that adds anything to the phase 3 results.

Caveats. Every trial was funded and run by Novo Nordisk, and REDEFINE 4 has so far been released only as a company announcement rather than a peer-reviewed paper 3. Gastrointestinal adverse events affected 79.6% of the CagriSema group in REDEFINE 1 and 72.5% in REDEFINE 2 12. The headline figures quoted in press coverage are often the efficacy estimand — what happens if people take the drug as directed — while the treatment-policy estimand, which counts everyone as randomised, is lower; REDEFINE 4 reported 23.0% and 20.2% respectively for the same participants 3. There is no published cardiovascular outcome trial for the combination, and no long-term safety data beyond 68 to 84 weeks. Because the components cannot be dosed separately, the trials cannot say which component causes a given adverse event.

What it is used for

  • Chronic weight management in obesity, or overweight with a weight-related comorbid condition — the indication submitted to the FDA in December 2025, not an approved indication anywhere 4
  • Weight management and glycaemic control in type 2 diabetes — studied in REDEFINE 2, not approved 2
  • Of interest as the first once-weekly combination of a GLP-1 receptor agonist with an amylin analogue to reach a regulatory filing 4

Dosing

Dose
2.4 mg cagrilintide with 2.4 mg semaglutide, once weekly, after a 16-week escalation — this is the trial dose, not a recommended regimen
Frequency
once weekly
Route
Subcutaneous
Duration
68 weeks in REDEFINE 1 and 2; 84 weeks in REDEFINE 4
  • The figures below describe what was given in registered clinical trials under medical supervision. They are not a recommended schedule, and no regulator has approved a dose of this combination anywhere.
  • In REDEFINE 1 and REDEFINE 2, both components were escalated together over a 16-week period to the maintenance dose of cagrilintide 2.4 mg with semaglutide 2.4 mg once weekly, which was then continued for the remainder of the trial 12. This site does not reproduce the individual escalation steps, because they are set out in the trial protocols rather than in the published papers and have not been verified here.
  • The two components cannot be titrated separately. That is a design feature of the product and a real constraint: someone who cannot tolerate the amylin component has no option but to reduce both.
  • Products sold online under this name are not the trial product. There is no way for a purchaser to confirm the ratio, the identity of either peptide, or sterility.
  • A self-dosing practice nonetheless circulates, and it is captured in the protocols section below as a social fact rather than a validated schedule. Two forms circulate: vials sold pre-labelled 'CagriSema', and — more commonly discussed — buying separate cagrilintide and semaglutide powders and combining them, either in one syringe or as two injections. The doses passed around are copied wholesale from the REDEFINE escalation ladder, which is itself just the Wegovy semaglutide ladder applied to both peptides at once; none of it has any published basis for self-mixed material 7.

These figures describe what the literature and published protocols report. They are not advice and not a dosing instruction.

Protocols

REDEFINE 1 trial schedule (obesity without diabetes)

published trial

Source: REDEFINE 1, phase 3a, ClinicalTrials.gov NCT05567796

Weeks 1-16Dose escalation of both components towards the maintenance dose
Weeks 17-68Cagrilintide 2.4 mg with semaglutide 2.4 mg, subcutaneously once weekly

The trial registry describes a 16-week escalation period followed by 52 weeks of maintenance dosing. This is a research protocol run under supervision in 3,417 people, not a treatment recommendation, and the combination is not approved.

Self-mixed user schedule (weekly subcutaneous)

user protocol — not validated

Source: User reports on GLP-1 and peptide forums together with vendor vial labelling

This is not a validated schedule. It is a pattern that circulates among users and sellers, reproduced because it is what people actually follow — not because it has been tested. No trial established these doses, this interval or this duration, and nobody is checking what is in the vial. Treat every number below as an assertion, not a finding.

Reported weeks 1-40.25 mg cagrilintide + 0.25 mg semaglutide once weekly
Reported weeks 5-80.5 mg + 0.5 mg once weekly
Reported weeks 9-121 mg + 1 mg once weekly
Reported weeks 13-161.7 mg + 1.7 mg once weekly
Reported maintenance2.4 mg + 2.4 mg once weekly

These figures come from user reports and vendor labelling and have no published basis for self-mixed or grey-market material. The ladder is copied verbatim from the REDEFINE trial escalation, which readers should recognise as the ordinary Wegovy semaglutide ladder applied to both peptides simultaneously — a strong sign the numbers are borrowed, not derived from anything anyone measured in a self-mixing context. The practical reality is messier than the tidy table: people combine two separately bought powders whose true content is unverifiable, so the actual 1:1 ratio cannot be confirmed; some draw both into one syringe while others inject separately; and the milligram-versus-microgram trap (0.25 mg is 250 mcg, and a syringe 'unit' is a volume) sits on top of two independent concentration calculations rather than one. No compatibility or stability data exist for the mixture, and the FDA has warned about firms selling GLP-1 compounds under 'research use only' labels while supplying human dosing instructions 78.

Schedules are reproduced as their source states them. Units, IU and milligrams explains why the figures are not interchangeable between products.

Reconstitution

Storage
No approved product exists, so no manufacturer storage instruction can be quoted. Both component peptides require refrigeration in their trial presentations.

Worked example

Not applicable. In the trials CagriSema was supplied as a ready-to-use subcutaneous injection; there is nothing to reconstitute and no licensed product on the market to buy.

This site does not provide a reconstitution calculator for this entry. Material sold online under this name is of unknown composition, and a calculator would imply a known concentration that nobody can verify.

Safety

Side effects

  • Gastrointestinal events dominate: nausea, vomiting, diarrhoea, constipation and abdominal pain, reported by 79.6% of the combination group in REDEFINE 1 against 39.9% on placebo, and by 72.5% against 34.4% in REDEFINE 2 12
  • Most gastrointestinal events were transient and mild to moderate in severity, and concentrated in the escalation phase 12
  • Decreased appetite, which is the intended effect but is reported as an adverse event when marked
  • Loss of lean mass alongside fat mass, as with other agents producing weight loss of this magnitude
  • Hypoglycaemia risk in type 2 diabetes, particularly in combination with insulin or a sulfonylurea 2
  • The class effects of GLP-1 receptor agonists — gallbladder disease, pancreatitis, increased heart rate, delayed gastric emptying with implications for anaesthesia — apply through the semaglutide component; see that entry
  • Injection site reactions

Do not use if

  • There is no approved product and therefore no approved contraindication list. What follows is inferred from the components and from the trial exclusion criteria, and should be read as that
  • The contraindications of semaglutide apply: personal or family history of medullary thyroid carcinoma, multiple endocrine neoplasia syndrome type 2, and known hypersensitivity
  • Pregnancy and breastfeeding
  • History of pancreatitis
  • Severe gastrointestinal disease including gastroparesis
  • Concurrent use of another GLP-1 receptor agonist or another amylin analogue would be duplicative and was not studied

Interactions

Not characterised for the combination as such. Delayed gastric emptying may alter the absorption of oral medicines, which matters most for drugs with a narrow therapeutic index. In type 2 diabetes, adding this combination to insulin or a sulfonylurea raises hypoglycaemia risk and generally requires reducing those agents 2. Anaesthesia guidance on modified preoperative fasting for GLP-1 receptor agonists applies through the semaglutide component. Interactions specific to cagrilintide are covered in its own entry; pramlintide, the older amylin analogue, carries a boxed warning about severe hypoglycaemia when given with insulin, and that history is the reason the combination with insulin deserves care.

Sources