CagriSema Research: The REDEFINE Phase 3 Programme, Precisely

What is CagriSema?

CagriSema is the development name Novo Nordisk uses for cagrilintide and semaglutide administered together. The two molecules come from different hormone families and engage different receptors, which is the reason the pairing was constructed rather than a claim about what it achieves:

• Cagrilintide is a lipidated, long-acting analogue of amylin — the pancreatic hormone co-secreted with insulin. It is not an incretin and not a GLP-1 receptor agonist. Amylin receptors are assemblies rather than single proteins: the calcitonin receptor paired with a receptor activity-modifying protein. Its development is described by Kruse et al. (2021, J Med Chem). Full detail on the cagrilintide research page.
• Semaglutide is a GLP-1 receptor agonist with an acylated, albumin-binding design and an extensive independent trial record of its own. Full detail on the semaglutide research page.

The form of the combination changed across the programme, and the distinction is easy to miss. The earlier trials co-administered the two peptides — separate preparations given concomitantly. The later phase 3 work used a fixed-dose combination, described as such in REDEFINE 5, where cagrilintide 2.4 mg and semaglutide 2.4 mg were delivered as one once-weekly product. Reading trial reports as though these were interchangeable is the commonest error in secondary coverage of this compound.

Why this pairing, and where it came from

The programme has a visible lineage. Enebo et al. (2021, Lancet) reported the phase 1b trial examining safety, tolerability, pharmacokinetics and pharmacodynamics when multiple doses of cagrilintide were given concomitantly with semaglutide 2.4 mg — the first study in the combination line and the point at which “cagrilintide plus semaglutide” became a research object rather than two separate compounds. Frias et al. (2023, Lancet) followed with a randomised, active-controlled phase 2 trial of the co-administered pair in people with type 2 diabetes.

The design rationale, stated neutrally, is that the two components act at unrelated receptors, so a trial of the pair asks a question that neither single-agent trial answers. That is a statement about experimental design, not about outcome: the reason a combination is worth studying is precisely that its result is not predictable from the components. Everything below is what the resulting trials measured, attributed to the trials and to the sponsor that ran them.

Reference data — per component

CagriSema has no molecular identity of its own; it is two molecules. Reference data is therefore given per component, drawn from the public chemical record. Cagrilintide’s full residue sequence is not published in a form that could be sourced here and is omitted rather than estimated.

One shared feature is analytically relevant: both are large, acylated peptides that carry a fatty side chain enabling reversible albumin binding. A missing or truncated acyl chain shifts the measured mass downward without necessarily producing an obviously abnormal chromatogram — a failure mode the verification section returns to.

The REDEFINE programme — what each trial randomised

These are reported as trial designs and published results, attributed to their investigators and to Novo Nordisk, which funded and ran the programme. Nothing here is a statement in Cellworks’ own voice about what any compound does.

REDEFINE 1 (Garvey et al., NEJM 2025; NCT05567796)

A phase 3a, 68-week, multicentre, double-blind, placebo-controlled and active-controlled trial in adults without diabetes who had a BMI of 30 or higher, or 27 or higher with at least one obesity-related complication. A total of 3,417 participants were randomised in a 21:3:3:7 ratio to cagrilintide–semaglutide (n=2,108), semaglutide 2.4 mg alone (n=302), cagrilintide 2.4 mg alone (n=302), or placebo (n=705), with lifestyle intervention in all groups. The coprimary endpoints were the relative change in body weight and a reduction of 5% or more from baseline to week 68, in each case for the combination compared with placebo. The trial reported an estimated mean change in body weight of −20.4% with the combination versus −3.0% with placebo (estimated difference −17.3 percentage points; 95% CI −18.1 to −16.6; P<0.001). Gastrointestinal adverse events were reported in 79.6% of the combination group and 39.9% of the placebo group, described by the investigators as mainly transient and mild-to-moderate.

REDEFINE 2 (Davies et al., NEJM 2025)

The phase 3 counterpart in adults with overweight or obesity and type 2 diabetes — a different population, published alongside REDEFINE 1 in the same issue.

REDEFINE 5 (Yamauchi et al., Lancet Diabetes Endocrinol 2026; NCT05813925)

A double-blind, parallel-group phase 3a trial across 21 sites in Japan and one in Taiwan, in which 331 participants were randomised 1:1 to once-weekly subcutaneous cagrilintide–semaglutide as a fixed-dose combination or to semaglutide 2.4 mg alone, plus lifestyle intervention, for 68 weeks. The primary endpoint was relative change in body weight at week 68. The trial reported an estimated mean change of −18.4% in the combination group versus −11.9% in the semaglutide group (estimated treatment difference −6.5 percentage points; 95% CI −8.4 to −4.6; P<0.0001). Adverse events were reported in 87% and 84% of the two groups respectively, most commonly gastrointestinal disorders.

Further reports and ongoing work

• Verma et al. (2026, Hypertension) — a secondary blood-pressure analysis of REDEFINE 1.
• REDEFINE 3 (NCT05669755) — a cardiovascular-outcomes study, listed as active and not recruiting; no primary publication at the time of writing.
• Registered head-to-head work against tirzepatide (NCT06131437 and NCT06221969) — comparisons with a dual incretin agonist, not combinations with it. See tirzepatide.

What these trials cannot answer

This is where a combination programme demands more care than a single-agent one, and where the REDEFINE results are most often over-read.

• REDEFINE 1 was powered against placebo, not against its monotherapy arms. The coprimary endpoints named placebo as the comparator. The semaglutide-alone and cagrilintide-alone arms enrolled 302 participants each against 2,108 on the combination — a 7:1 imbalance. Those arms are reference groups that contextualise the result; they are not a powered head-to-head test of combination versus component, and treating a difference between them as an established comparison misreads the design.
• REDEFINE 5’s comparison is real but bounded. It was designed as combination versus semaglutide alone, which makes it the more direct comparison of the two — but it randomised 331 participants in an east Asian population across 22 sites, over 68 weeks, with the sponsor’s employees among the authors. Its own investigators frame the conclusion as supporting use in individuals from east Asia. Generalising it beyond that is the reader’s inference, not the trial’s finding.
• Neither trial isolates what cagrilintide contributes. A combination design characterises the combination. The independent single-agent evidence for cagrilintide remains a phase 2 dose-finding trial, which its own page sets out; REDEFINE was not built to substitute for it and should not be read as though it were.
• Every trial named here was funded by the manufacturer. Novo Nordisk funded and ran the programme, and Novo Nordisk employees are listed among the authors of each publication. That is disclosed in the papers themselves and is stated here because it is part of reading the evidence, not because it invalidates it.
• The trials used a manufactured pharmaceutical under medical supervision. Nothing in this literature describes, characterises or applies to research-grade supplied material, and no property of any supplied reagent can be inferred from it.

Evidence status, regulatory status, and what is not established

What is established: a phase 1b, a phase 2 and multiple phase 3 randomised trials of the combination, published in high-impact peer-reviewed journals with registered protocols; a design rationale grounded in two unrelated receptor systems; and secondary analyses of REDEFINE 1. By the standards of the peptide-combination market, that is an unusually complete record — and stating so is a comment on the evidence, not an endorsement of the product.

What is not established: any separation of each component’s individual contribution within the combination result; any long-term outcome data, since the cardiovascular-outcomes trial has not reported; any characterisation of research-grade material; and any claim about a co-formulated preparation supplied outside the trial setting, which is a different material made by a different process and covered by none of this literature.

On regulatory status: CagriSema is investigational and has not been approved by the FDA, the EMA, BPOM (Indonesia) or any other regulator. Novo Nordisk announced in December 2025 that it had submitted a New Drug Application to the FDA on the basis of the REDEFINE programme — a submission, which is not an approval and does not become one by being reported. Compare semaglutide, one of its components, which is approved in its own right. This page reports what trials measured, makes no efficacy or benefit claim in its own voice, gives no dosing guidance, and describes material that is not for human or veterinary use.

How to verify this compound yourself

A vial containing two acylated peptides raises the same analytical problem as any blend, sharpened by the fact that these two are chemically similar in size and design:

• Resolution before purity. Cagrilintide (≈ 4409 Da) and semaglutide (≈ 4114 Da) are both large lipidated peptides. A reversed-phase method must actually separate them before any purity figure means anything; a single percentage that does not state whether the peaks were resolved, and which peak it refers to, is not an interpretable number.
• Two masses, confirmed independently. Mass-spec identity should return both expected masses. For either component a missing acyl chain shifts the mass downward, and cagrilintide additionally carries an intramolecular disulfide whose reduced form differs by two hydrogen mass units.
• Per-component content. A preparation quoted as two separate milligram figures needs two separate quantitation results. Purity does not answer how much of each peptide is present.
• Endotoxin and sterility — where tested, quality attributes reported independently of chemical purity.

Context on why this matters for this compound class specifically: a 2026 preprint by Mendias and Awan analysed 6,441 samples across fourteen compounds, cagrilintide and semaglutide among them, drawn from a large public independent-testing dataset. It reported that 41.6% to 71.1% of samples failed basic quality criteria depending on which of two acceptance frameworks was applied, with measurable endotoxin in 15%. It is a preprint and has not completed peer review; it is cited because it is the largest published analysis of this exact material class.

See how to read a COA, how to verify peptide purity and how to spot a fake COA. Check the exact batch on the self-serve verify tool.

Research-grade sourcing and verification

CagriSema is not held in Cellworks stock. It appears in the sourcing catalogue as available to order, listed by the supplier at per-component pairings of 2.5 mg + 2.5 mg, 5 mg + 5 mg and 10 mg + 10 mg. Sourcing takes roughly two to three weeks, no price is quoted until availability is confirmed, and there is no cart button.

Anything sourced this way is a laboratory research reagent with a per-batch Certificate of Analysis. To be unambiguous: “CagriSema” names a clinical trial intervention. Supplied research material is not that intervention, was not made by its manufacturer, and inherits none of its trial data.

Frequently asked questions

Literature cited

1. Garvey WT, Blüher M, Osorto Contreras CK, et al. “Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity.” (REDEFINE 1) N Engl J Med. 2025;393(7):635–647. PMID 40544433. pubmed.ncbi.nlm.nih.gov/40544433.
2. Davies MJ, Bajaj HS, Broholm C, et al. “Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes.” (REDEFINE 2) N Engl J Med. 2025;393(7):648–659. PMID 40544432. pubmed.ncbi.nlm.nih.gov/40544432.
3. Yamauchi T, Becker NP, Hagemann CA, 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.” Lancet Diabetes Endocrinol. 2026;14(6):450–462. PMID 42009015. pubmed.ncbi.nlm.nih.gov/42009015.
4. 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.” Lancet. 2021;397(10286):1736–1748. PMID 33894838. pubmed.ncbi.nlm.nih.gov/33894838.
5. 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.” Lancet. 2023;402(10403):720–730. PMID 37364590. pubmed.ncbi.nlm.nih.gov/37364590.
6. Verma S, Böttcher M, Brown P, et al. “CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1.” Hypertension. 2026;83(2):e26055. PMID 41328546. pubmed.ncbi.nlm.nih.gov/41328546.
7. Kruse T, Hansen JL, Dahl K, et al. “Development of Cagrilintide, a Long-Acting Amylin Analogue.” J Med Chem. 2021;64(15):11183–11194. PMID 34288673. pubmed.ncbi.nlm.nih.gov/34288673.
8. Mendias CL, Awan TM. “Evaluation of Research Grade Peptides Marketed Directly to Consumers Reveals Extensive Variability in Purity and Measured Abundance.” Preprints (not peer reviewed). 2026. doi.org/10.20944/preprints202604.1748.v1.
9. ClinicalTrials.gov. REDEFINE 1, NCT05567796; REDEFINE 3, NCT05669755; REDEFINE 5, NCT05813925.