Cagrilintide + Semaglutide

Technical data

INN name

Cagrilintide + Semaglutide

Identity and composition

Cagrilintide + Semaglutide (CagriSema) is a fixed-dose co-formulation of two long-acting acylated peptides, in advanced clinical research for body weight management. It combines an amylin analog (cagrilintide) with a GLP-1 receptor agonist (semaglutide) in a single weekly subcutaneous administration.

This presentation is offered as 10 mg reference material for laboratory use. As for its chemical identity, a single CAS number, molecular weight or molecular formula does not apply to the coformulation, since it is the combination of two distinct peptides; therefore these data are not reported as unique verifiable constants. Among its synonyms and designations are CagriSema, cagrilintide/semaglutide y fixed-dose combination GLP-1/amylin.

Product for research use.

Mechanism of action

The proposed mechanism combines two separate but complementary pathways for the regulation of appetite and body weight (PMID 36883831).

• Cagrilintide: long-acting amylin analog that acts as an agonist of the amylin (and calcitonin) receptor. In research models it has been described to suppress appetite mainly through neuronal populations of the dorsal vagal complex and the brainstem, as well as homeostatic and hedonic regions.
• Semaglutide: acylated GLP-1 receptor agonist that, according to the literature, reduces appetite via GLP-1 receptors, increases insulin secretion, and delays gastric emptying.

It has been proposed that both mechanisms exert an additive or complementary effect on appetite reduction (PMID 36883831). The two components use a diacid fatty-acid side chain that allows reversible binding to albumin, which makes weekly dosing feasible.

Pharmacokinetics

It is designed for subcutaneous administration once a week. Both components are peptides acylated with a C20 fatty diacid side chain that allows binding to albumin and a prolonged half-life, compatible with weekly dosing.

No specific numerical half-life value confirmed for the coformulation is available in the open sources consulted, so this parameter is described only qualitatively.

Scientific evidence

The evidence comes from advanced clinical research; it is not a supplement. The phase 3 REDEFINE program evaluated the coformulation in overweight and obesity. The trial REDEFINE 1 was a 68-week, double-blind, placebo- and active-comparator-controlled phase 3 study, in 3,417 adults with obesity or overweight with complications and without type 2 diabetes (NCT05567796).

In that trial it was reported that the co-formulation met its primary objective, with a mean weight reduction of around 20.4% (reported up to 22.7% according to the efficacy estimand) versus about 3% with placebo, and superior to cagrilintide or semaglutide as monotherapy (NCT05567796).

It is important to note that the efficacy figures vary depending on the reported estimand (treatment vs. efficacy). As of the date of the report, the compound was in the process of regulatory application and has also been studied in type 2 diabetes. The evidence must be interpreted in the context of a compound still in development.

Research applications

Product for research use.

Aimed at:

• In vitro and preclinical-model research on amylin and GLP-1 signaling pathways.
• Reference studies and analytical characterization of long-acting peptide coformulations.
• Experimental work on mechanisms of appetite and body weight regulation in laboratory contexts.

Not applicable for:

• clinical use, therapeutic use, diagnostic or preventive use in humans.
• Use in domestic or companion animals for treatment purposes.
• Any application outside a controlled research environment.

Research protocols

In the study context, the co-formulation has been investigated as cagrilintide 2.4 mg + semaglutide 2.4 mg in weekly subcutaneous administration (NCT05567796). The phase 3 trial REDEFINE 1 had a duration of 68 weeks (NCT05567796).

These doses correspond to clinical research protocols and are cited solely for documentary purposes; they do not constitute a use guideline. The 10 mg presentation of this material is handled according to the experimental objectives of each laboratory. No other doses or detailed titration schemes are available in the consulted literature, so none are specified here.

Reconstitution

As a general standard laboratory guide for lyophilized peptides, reconstitution is usually performed with bacteriostatic water (water with approximately 0.9% benzyl alcohol), which helps limit microbial growth in preparations for repeated use.

Common practices:

• Add the diluent, letting it run slowly down the wall of the vial, without directing the stream directly onto the powder.
• Do not shake vigorously; swirl the vial gently until completely dissolved to reduce mechanical stress on the peptide.
• Adjust the diluent volume according to the working concentration desired for the 10 mg of material.

These indications are for general laboratory handling and do not imply preparation for use in humans.

Stability and storage

As standard peptide handling practice:

• Lyophilized (powder): is usually kept refrigerated and, for prolonged storage, frozen, protected from light and moisture. In their dry form, acylated peptides tend to better maintain their integrity over time. - Reconstituted (in solution): once dissolved it should be kept refrigerated and used within a short window, avoiding repeated freeze-thaw cycles.

These ranges correspond to general laboratory handling knowledge; no specific numerical stability data are available in the consulted literature for this coformulation.

Safety profile

The reported safety profile is consistent with the incretin/amylin class, with predominantly gastrointestinal adverse events, such as nausea, vomiting and diarrhea (NCT05567796).

The open sources consulted did not detail specific quantitative rates nor new safety signals beyond what is expected for the class, so those percentages are not reported here. For complete safety information it is advisable to refer to the primary publication and to regulatory labels when available.

As this is a product for exclusive research use, it must be handled with standard laboratory precautions and kept out of the reach of unauthorized persons.

Comparative context

Within its class, the coformulation combines two mechanisms that are usually studied separately: amylin receptor agonism (cagrilintide) and GLP-1 receptor agonism (semaglutide).

In REDEFINE 1, it was observed that the combination produced greater weight loss than each component in monotherapy and than placebo, with approximate values of 20.4% for the coformulation, 11.5% for cagrilintide 2.4 mg, 14.9% for semaglutide 2.4 mg, and about 3% for placebo, which is consistent with an additive effect of the dual amylin + GLP-1 mechanism (NCT05567796).

It is described as the first weekly combination of a GLP-1 analog and amylin for weight management, which distinguishes it from conventional incretin monotherapies.

History and development

Cagrilintide was developed as a long-acting amylin analog and was studied in combination with the GLP-1 receptor agonist semaglutide, seeking to exploit additive mechanisms on appetite suppression (PMID 36883831).

The combination, known as CagriSema, advanced to the phase 3 REDEFINE program, which evaluated the coformulation in overweight and obesity and also included studies in type 2 diabetes (NCT05567796). As of the report date, the compound was in the process of regulatory submission, and it is described as the first weekly combination of a GLP-1 analog and amylin described for weight management.

FAQ

Certificate of analysis per batch

Batch of Cagrilintide + Semaglutide with a certificate of analysis published in the COA catalog:

• Lot EXO010626132A — 10 mg, issued 2026-05-30

Scientific references (4)

Peer-reviewed literature on Cagrilintide + Semaglutide, with its PubMed identifier when available:

• Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Concomitant Administration of Multiple Doses of Cagrilintide with Semaglutide 2.4 mg for Weight Management (Enebo, et al. · The Lancet · 2021) PMID 33894838.
• 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 (Frias, et al. · The Lancet · 2023) PMID 37364590.
• Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1) (Garvey, et al. · The New England Journal of Medicine · 2025) PMID 40544433.
• Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2) (Davies, et al. · The New England Journal of Medicine · 2025) PMID 40544432.

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