CagriSema Research, Specifications & Scientific Information

Introduction

CagriSema is the only entry in this category that is not a molecule. It is two of them: cagrilintide, a long-acting analogue of the hormone amylin, and semaglutide, an acylated agonist at the GLP-1 receptor, administered together once a week.

That distinction governs everything else on this page. A combination has no sequence, no molecular formula, no CAS registry number and no UNII, because those are properties of substances and a combination is not one. Every such field here is published as unknown, and the identifiers that do exist belong to the two components and are recorded on their own pages. A supplier listing offering "CagriSema" as a single reagent with a single CAS number is describing something that does not exist as a defined substance.

What the combination does have is a clinical record, and a substantial one: a phase 1b pharmacokinetic study, a phase 2 trial against each component alone, and a phase 3 programme running under two names, REDEFINE in obesity and REIMAGINE in type 2 diabetes.

This page is a reference record. It sets out what has been published about the combination's pharmacology and clinical literature, with every source resolved against PubMed, Crossref or ClinicalTrials.gov at the time the page was built. It describes research. It does not describe use in people or animals, and it carries no guidance of any kind on handling the material.

What Is CagriSema?

CagriSema is an investigational fixed-ratio combination developed by Novo Nordisk. It has not been approved by the U.S. Food and Drug Administration.

Its regulatory position has a wrinkle the other entries in this library do not: one of its two components is an approved active ingredient and the other is not. Semaglutide is the active ingredient of finished pharmaceutical products that hold FDA approval. Cagrilintide is investigational. Neither of those facts has any bearing on the combination, which is a separate product and holds no approval of its own — and neither has any bearing on research-grade material supplied for laboratory use.

One further distinction runs through the literature and is easy to miss. The early trials co-administered the two peptides as separate injections ^[1]. The later phase 3 trials used a fixed-ratio combination delivered from a single device ^[5]. These are different products even at identical amounts, and a result from one is not automatically a result about the other.

CagriSema Specifications

CagriSema is not a molecule and has no sequence, formula, mass, CAS registry number or UNII of its own, which is why every one of those fields is published here as unknown rather than filled. It is a fixed-ratio combination of two separately characterised peptides, each of which has its own register entries: cagrilintide, CAS 1415456-99-3, UNII AO43BIF1U8, PubChem CID 171397054, a long-acting amylin analogue; and semaglutide, CAS 910463-68-2, UNII 53AXN4NNHX, PubChem CID 56843331, an acylated GLP-1 analogue. The identifiers, sequences and structural characteristics of the two components are set out on their own pages in this library. The early clinical work co-administered the two as separate injections, and the later phase 3 trials used a fixed-ratio combination delivered from a dual-chamber device; the distinction between co-administration and co-formulation matters when reading the literature, because the two are not the same product even at the same amounts.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does CagriSema Work?

The combination engages two receptor systems that do not overlap.

Amylin, through cagrilintide. Amylin is co-secreted with insulin from pancreatic beta cells and acts through the calcitonin receptor in complex with receptor activity-modifying proteins, forming the amylin receptors. Its signalling reaches hindbrain circuits that regulate food intake — a different set of circuits, and a different receptor family, from the incretin system.

GLP-1, through semaglutide. The GLP-1 receptor is a class B1 G protein-coupled receptor on pancreatic islet cells and at central nervous system sites, whose activation modulates glucose-dependent insulin secretion and reduces calorie intake.

The rationale stated for the pairing is that the two have complementary effects on glycaemic control and on body mass ^[6] — complementary rather than additive, meaning the claim is about acting through different routes rather than about doing more of the same thing.

A practical question for any combination is whether the components interfere with each other pharmacokinetically. For this pair the answer was measured directly, and it was no: cagrilintide exposure was proportional to the amount administered and did not affect semaglutide exposure or elimination ^[1]. The two also have similar residence times — reported half-lives of 159 to 195 hours for cagrilintide across the range studied, and 145 to 165 hours for semaglutide 2.4 mg — which is what makes a single weekly administration of both workable.

What Is CagriSema Being Researched For?

Registered clinical research on the combination has covered:

• Obesity and overweight without diabetes — the REDEFINE phase 3a programme ^[4].
• Obesity and overweight with type 2 diabetes — a phase 2 trial and a phase 3a trial ^{[2, 3]}.
• Glycaemic control in type 2 diabetes — the REIMAGINE phase 3 programme, with a glycated haemoglobin primary endpoint rather than an anthropometric one ^[6].
• East Asian populations — a phase 3a trial in Japan and Taiwan against semaglutide alone ^[5].
• Cardiovascular outcomes in participants with established cardiovascular disease — a registered phase 3 trial enrolling more than seven thousand participants ^[11].

Each of those is research into a pharmaceutical product candidate, conducted by its sponsor under a registered protocol. None of it is research into, or evidence about, research-grade material supplied for laboratory use.

Human Research on CagriSema

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

REDEFINE 1 — phase 3a in adults without diabetes

Population. 3,417 adults without diabetes with a body-mass index of 30 or higher, or 27 or higher with at least one obesity-related complication. Randomised 21:3:3:7 to cagrilintide-semaglutide 2.4 mg each (2,108), semaglutide 2.4 mg alone (302), cagrilintide 2.4 mg alone (302) or placebo (705), with lifestyle interventions in every group ^{[4, 10]}.

Endpoint and duration. Coprimary endpoints at week 68: the relative change in body mass, and a reduction of 5% or more, both for the combination against placebo. Reductions of 20%, 25% and 30% or more were confirmatory secondary endpoints. Estimates used the treatment-policy estimand ^[4].

Result. The estimated mean percent change in body mass from baseline to week 68 was −20.4% with the combination against −3.0% with placebo — estimated difference −17.3 percentage points, 95% CI −18.1 to −16.6, P < 0.001. Participants receiving the combination were more likely than those on placebo to reach reductions of 5%, 20%, 25% and 30% or more, P < 0.001 for all ^[4].

Adverse events. Gastrointestinal adverse events — nausea, vomiting, diarrhoea, constipation or abdominal pain — affected 79.6% of the combination group and 39.9% of the placebo group, mainly transient and mild to moderate ^[4].

Limitations. The trial's coprimary comparison is against placebo, not against either component. Its two active-comparator arms hold 302 participants each against 2,108 in the combination arm — a ratio chosen for safety characterisation rather than for a powered head-to-head comparison, and the reason this page does not quote a component comparison from this trial. Sixty-eight weeks, with anthropometric endpoints rather than clinical outcomes.

REDEFINE 2 — phase 3a in adults with type 2 diabetes

Population. 1,206 adults in 12 countries with a body-mass index of 27 or more, glycated haemoglobin 7 to 10%, and type 2 diabetes, randomised 3:1 to the combination at 2.4 mg each (904) or placebo (302), with lifestyle intervention ^{[3, 9]}.

Endpoint and duration. Two primary endpoints at week 68: the percent change in body mass, and the percentage of participants with a reduction of at least 5%. Treatment-policy estimand ^[3].

Result. Estimated mean change in body mass from baseline to week 68 was −13.7% with the combination against −3.4% with placebo — estimated difference −10.4 percentage points, 95% CI −11.2 to −9.5, P < 0.001. More participants reached reductions of 5% or more, and of at least 10%, 15% and 20%, P < 0.001. Glycated haemoglobin of 6.5% or below was reached by 73.5% of the combination group against 15.9% on placebo ^[3].

Adverse events. Gastrointestinal adverse events were reported by 72.5% of the combination group and 34.4% of the placebo group, most transient and mild or moderate ^[3].

Limitations. Placebo-controlled with no active comparator, so the trial says nothing about how the combination compares with either component in this population. The anthropometric result here is smaller than in the non-diabetic population of REDEFINE 1, which is a consistent pattern across this drug class and is worth noting rather than explaining.

REDEFINE 5 — against semaglutide alone in Japan and Taiwan

Population. 331 participants at 21 sites in Japan and one in Taiwan, aged 18 or over with a body-mass index of at least 27 kg/m² and at least two obesity-related complications, or at least 35 kg/m² with at least one, per Japanese guidelines, with or without type 2 diabetes. 68% male; 24% had type 2 diabetes ^[5].

Endpoint and duration. Primary endpoint the relative change in body mass from baseline to week 68. Randomised 1:1 to the fixed-ratio combination or to semaglutide alone, both escalated to 2.4 mg, plus lifestyle intervention. The primary estimand was the trial-product estimand ^[5].

Result. Estimated mean change in body mass at week 68 was −18.4% (SE 0.7) with the combination against −11.9% (0.7) with semaglutide alone — estimated treatment difference −6.5 percentage points, 95% CI −8.4 to −4.6, p < 0.0001 ^[5].

Adverse events. Reported by 143 of 164 participants (87%) on the combination and 141 of 167 (84%) on semaglutide; the most common were gastrointestinal disorders, in 53% against 51%. Seventeen participants (10%) discontinued the combination and ten (6%) discontinued semaglutide. One death occurred in the semaglutide group and was not judged treatment-related by the investigator ^[5].

Limitations. 331 participants in an east Asian population selected by Japanese obesity criteria, which differ from those used elsewhere; the result is specific to that population. The primary analysis used the trial-product estimand — which assumes treatment was used as intended — and missing data at week 68 were imputed. Both choices tend to produce larger estimates than a treatment-policy analysis.

REIMAGINE 2 — phase 3 with a glycaemic primary endpoint

Population. 2,713 participants randomised from 3,593 screened, in 30 countries, aged 18 or over with inadequately controlled type 2 diabetes (glycated haemoglobin 7.0–10.5%) on metformin with or without an SGLT2 inhibitor, and a body-mass index of 25 kg/m² or more. 42.9% female; 81.3% White; mean baseline glycated haemoglobin 8.2% ^{[6, 12]}.

Endpoint and duration. Primary endpoint the change in glycated haemoglobin from baseline to week 68 with the combination at 2.4 mg each against semaglutide 2.4 mg. Six arms in all, including both components alone, a lower-amount combination, and placebo ^[6].

Result. On the efficacy estimand, mean glycated haemoglobin change was −1.91 percentage points (SE 0.04) with the combination against −1.75 (0.04) with semaglutide 2.4 mg — estimated treatment difference −0.16 percentage points, 95% CI −0.27 to −0.05, p = 0.0035. Of those randomised, 2,595 (95.7%) completed the study and 2,376 (87.6%) were on treatment at week 68 ^[6].

Adverse events. Reported in 86.9% of the combination group at 2.4 mg each, 81.2% of the semaglutide 2.4 mg group, 82.2% of the cagrilintide 2.4 mg group and 70.5% of the placebo group. The most common in the active groups were gastrointestinal disorders ^[6].

Limitations. The glycaemic difference is 0.16 percentage points, statistically significant in a trial of 2,713 participants and small in absolute terms — a useful illustration of the gap between significance and magnitude. The primary analysis used the efficacy estimand. Eighty-one percent of participants were White, which limits how far the result carries.

Phase 2 in type 2 diabetes, against each component alone

Population. 92 adults with type 2 diabetes and a body-mass index of 27 kg/m² or higher on metformin with or without an SGLT2 inhibitor, at 17 sites in the United States. 64% male; mean age 58 years ^{[2, 8]}.

Endpoint and duration. Primary endpoint the change from baseline in glycated haemoglobin over 32 weeks. Randomised 1:1:1 to the combination, semaglutide alone or cagrilintide alone, all escalated to 2.4 mg ^[2].

Result. Mean glycated haemoglobin change at week 32 was −2.2 percentage points with the combination, −1.8 with semaglutide and −0.9 with cagrilintide. The combination was superior to cagrilintide (estimated treatment difference −1.3 percentage points, 95% CI −1.7 to −0.8, p < 0.0001) but not to semaglutide (−0.4 percentage points, −0.8 to 0.0, p = 0.075). Mean change in body mass was −15.6% with the combination against −5.1% with semaglutide and −8.1% with cagrilintide, p < 0.0001 for both comparisons. Continuous-glucose-monitoring time in range moved from 45.9%, 32.6% and 56.9% at baseline to 88.9%, 76.2% and 71.7% at week 32 ^[2].

Adverse events. Reported by 68%, 71% and 80% of the three groups. Mild or moderate gastrointestinal events were most common; no level 2 or 3 hypoglycaemia and no fatal adverse events were reported ^[2].

Limitations. Thirty-one participants per arm — the reason the glycaemic comparison against semaglutide did not separate, and a trial this size cannot settle that question either way. Baseline time in range differed substantially between the three arms, which complicates reading the week-32 figures.

Phase 1b — pharmacokinetics of co-administration

Population. 96 participants randomised and 95 exposed, aged 18–55 with a body-mass index of 27.0–39.9 kg/m² and otherwise healthy, at a single United States centre. Mean age 40.6 years; 59% men; 54% Black or African American ^{[1, 7]}.

Endpoint and duration. Primary endpoint the number of treatment-emergent adverse events from baseline to end of follow-up. Six sequential overlapping cohorts, each randomised 3:1 to once-weekly cagrilintide at one of six amounts or matched placebo, in combination with semaglutide 2.4 mg, co-escalated over 16 weeks, four weeks at target, five weeks of follow-up ^[1].

Result. Of 566 adverse events in 92 participants, 207 (37%) were gastrointestinal disorders; most were mild to moderate, and the proportion of participants with at least one adverse event was similar across groups. Cagrilintide exposure was proportional to the amount administered and did not affect semaglutide exposure or elimination. Reported half-life was 159–195 hours for cagrilintide and 145–165 hours for semaglutide 2.4 mg. At week 20, mean percentage reductions in body mass were 15.7% and 17.1% for cagrilintide 1.2 and 2.4 mg against 9.8% for pooled placebo cohorts, and 15.4% for cagrilintide 4.5 mg against 8.0% for its matched placebo — all in combination with semaglutide 2.4 mg ^[1].

Limitations. The "placebo" arms received semaglutide 2.4 mg, so the comparison isolates the cagrilintide contribution and is not a comparison against no treatment. A single-centre study of 95 exposed participants designed for safety and pharmacokinetics; the authors state directly that larger and longer trials were needed.

Current Research Status

Status as of September 22, 2026. This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Why This Page Has No Preclinical Section

The preclinical record relevant to this combination belongs to its components, and it is published under their names rather than under the combination's. Discovery pharmacology, receptor characterisation and animal studies exist for cagrilintide and for semaglutide separately, and the corresponding sections appear on those two pages.

Reproducing that material here would mean presenting findings about one substance as findings about a different product. The entry's structured record therefore declares no animal and no in vitro research available, and no such section is rendered — which is what the absence of evidence is supposed to look like.

CagriSema vs Related Compounds

The distinction between CagriSema and the compounds it is usually set beside is that it is a combination of two molecules rather than one molecule with two activities, and nothing else is stated here.

One molecule or two

Tirzepatide and retatrutide are single peptides engaging two and three receptors respectively. CagriSema is two peptides, each engaging its own target. That difference governs how each is manufactured, characterised and identified — a single molecule has one CAS number and one sequence; a combination has none of its own.

Receptor systems

CagriSema reaches the amylin and calcitonin receptor family through cagrilintide, and the GLP-1 receptor through semaglutide. Neither tirzepatide nor retatrutide engages the amylin system at all; their additional targets are GIP and glucagon receptors.

Other amylin-directed compounds

Eloralintide is a selective amylin receptor agonist in earlier clinical development, studied both alone and alongside an incretin agonist.

Regulatory position

CagriSema is investigational. Semaglutide and tirzepatide are active ingredients of approved pharmaceutical products in the United States; cagrilintide and retatrutide are investigational. The approval of one component of a combination confers nothing on the combination.

No comparison of effect between these compounds is made on this page beyond the within-trial comparisons reported above. Where head-to-head trials exist they are registered, and their results belong to the papers that report them.

Chemical & Molecular Characteristics

There are none to state for CagriSema itself, and the reason is worth setting out rather than leaving as a row of blanks.

A combination is not a substance. Chemical identifiers — CAS registry numbers, UNII codes, PubChem compound identifiers, molecular formulae, sequences — are assigned to substances. A product containing two substances has no such identifier of its own, and none is published for CagriSema. Any listing that presents a single CAS number for "CagriSema" is either quoting one of the components' numbers or inventing one.

The components are fully characterised, separately. Cagrilintide carries CAS 1415456-99-3, UNII AO43BIF1U8 and PubChem compound identifier 171397054; it is a long-acting amylin analogue with a disulfide-bridged backbone and a fatty-diacid modification. Semaglutide carries CAS 910463-68-2, UNII 53AXN4NNHX and PubChem compound identifier 56843331; it is a 31-residue acylated GLP-1 analogue. Both have entries in this library setting out their sequences, structural modifications and register discrepancies.

Co-administration and co-formulation are different products. The phase 1b and phase 2 work administered the two peptides as separate injections ^{[1, 2]}. The phase 3 trials used a fixed-ratio combination in a single device ^[5]. For a page that records what was studied, that distinction has to be preserved: the pharmacokinetic finding that the components do not interfere with each other was established for co-administration, and it is the evidence on which the co-formulation rests rather than a finding about the co-formulation itself.

Frequently Asked Questions

Scientific References

1. 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 (London, England); 2021. PMID 33894838 doi:10.1016/S0140-6736(21)00845-X
2. 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 (London, England); 2023. PMID 37364590 doi:10.1016/S0140-6736(23)01163-7
3. Davies MJ, Bajaj HS, Broholm C, et al.. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes The New England journal of medicine; 2025. PMID 40544432 doi:10.1056/NEJMoa2502082
4. Garvey WT, Blüher M, Osorto Contreras CK, et al.. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity The New England journal of medicine; 2025. PMID 40544433 doi:10.1056/NEJMoa2502081
5. 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 The lancet. Diabetes & endocrinology; 2026. PMID 42009015 doi:10.1016/S2213-8587(25)00402-4
6. Buse JB, Bajaj HS, Dalskov SM, 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. PMID 42251859 doi:10.1016/S2213-8587(26)00125-7
7. A Research Study of How NNC0174-0833 Taken With Semaglutide Works in People Who Are Overweight or Obese 2018. NCT03600480
8. Research Study to Look at How Well Cagrilintide Together With Semaglutide Works in People With Type 2 Diabetes 2021. NCT04982575
9. A Research Study to See How Well CagriSema Helps People With Type 2 Diabetes and Excess Body Weight Lose Weight 2023. NCT05394519
10. A Research Study to See How Well CagriSema Helps People With Excess Body Weight Lose Weight 2022. NCT05567796
11. REDEFINE 3: A Research Study to See the Effects of CagriSema in People Living With Diseases in the Heart and Blood Vessels 2023. NCT05669755
12. A Research Study to See How Well CagriSema Compared to Semaglutide, Cagrilintide and Placebo Lowers Blood Sugar and Body Weight in People With Type 2 Diabetes Treated With Metformin With or Without an SGLT2 Inhibitor 2023. NCT06065540

Every identifier above is resolved against PubMed, Crossref or ClinicalTrials.gov at build time, and the title returned by the register is compared with the title stored here. A page does not publish if a reference fails to resolve.

Research-Use Information

For in vitro research use only. This material is a laboratory reagent. It is not a drug, food, dietary supplement, or cosmetic and is not for human or veterinary use, including ingestion, injection, or any other administration. No information on this page describes or implies any effect in humans or animals. Sold only to researchers under our Terms of Sale.