Semaglutide + Cagrilintide (Sema+Cagri) 4 mg + 4 mg PEN

One-Peptides SEMA+CAGRI 4mg+4mg PEN — semaglutide + cagrilintide blend in a pre-dissolved pen for laboratory research

SEMA+CAGRI 4mg+4mg PEN is a research reagent (Research Use Only) in the form of a pre-dissolved pen. It contains a blend of two peptides: semaglutide (4 mg) and cagrilintide (4 mg). CagriSema (Novo Nordisk) — a combination of the same two peptides — remains in phase III clinical trials (the REDEFINE 1–4 programme) and is not authorised as a medicine in the EU or the USA. Cagrilintide as a monotherapy is likewise in clinical trials — without authorisation. Semaglutide as a monotherapy, by contrast, is an authorised medicine (Ozempic, Wegovy, Rybelsus). Sema+Cagri 4mg+4mg PEN in the One Peptides catalogue is not clinical CagriSema — it comes from the chemical-reagent trade, not from EMA/FDA authorisation, and is not intended for use in humans.

CagriSema is the next step in the evolution of incretin pharmacology over the past decade. After GLP-1R monoagonists (semaglutide) and GLP-1R/GIPR dual agonists (tirzepatide), Novo Nordisk paired a GLP-1 agonist with an amylin receptor agonist — cagrilintide — developed specifically for this combination. The mechanisms act in parallel: GLP-1 centrally and through insulin secretion, amylin/calcitonin through gastric emptying and area postrema signalling. The REDEFINE programme tests the hypothesis that the effect on body weight will exceed what monoagonists achieve.

In the One Peptides catalogue, the same blend appears within a separate regulatory frame — as a research reagent (RUO) in a pre-dissolved pen format, in a fixed 1:1 ratio, with double the peptide content (4 mg + 4 mg) compared with the 2mg+2mg pen variant. The higher content provides a larger pool of material for experimental series; the pen format does not require lyophilisate reconstitution.

What the Sema+Cagri blend is — two peptides in one pen

Sema+Cagri 4mg+4mg PEN is a mixture of two separate peptides in a pre-dissolved solution:

• Semaglutide — 4 mg, a GLP-1 analogue
• Cagrilintide — 4 mg, a long-acting amylin/calcitonin analogue
• Total: 8 mg of peptides in the pen, fixed 1:1 ratio

The pen contains two distinct molecules dissolved in a single buffer — not a fusion or hybrid peptide. Each retains its own sequence, its own pharmacological class and its own pharmacokinetic profile. Combined class: GLP-1 agonist + amylin/calcitonin agonist.

Clinical kinship: the CagriSema combination — the same two peptides in injectable form — is in phase III of Novo Nordisk’s REDEFINE 1–4 programme (obesity and T2D). Earlier phase 1b/2a cagrilintide data were reported in 2021 (Enebo, Lau).

Semaglutide — a GLP-1 analogue

Semaglutide is a GLP-1 receptor (GLP-1R) monoagonist — a stabilised analogue of the endogenous glucagon-like peptide 1. The molecule comprises 31 amino acids, with a molecular weight of around 4113 Da.

C18 fatty-acid acylation enables reversible binding to serum albumin — albumin acts as a reservoir, the molecule circulates partly bound and is gradually released. A second modification stabilises the peptide against degradation by the DPP-4 enzyme. The result: a serum half-life of around 7 days (the once-weekly regimen in the Ozempic and Wegovy protocols).

The substance was developed by Novo Nordisk. As a monotherapy, semaglutide is authorised as Ozempic (T2 diabetes, FDA 2017), Wegovy (obesity, FDA 2021) and Rybelsus (oral form, FDA 2019). The EMA approved analogous indications in the EU.

Cagrilintide — a long-acting amylin/calcitonin analogue

Cagrilintide is a stabilised, long-acting analogue of amylin — a pancreatic hormone co-secreted with insulin by the β cells of the islets of Langerhans. Endogenous amylin has a very short half-life (a few minutes); cagrilintide was designed to overcome this limitation.

Class: a dual agonist — of the amylin receptor (AMY3R) and the calcitonin receptor (CTR). Structural modifications (including fatty-acid acylation) extend the half-life to a once-weekly regimen.

The mechanism reported in the literature: slowed gastric emptying (prolonged satiety), appetite modulation via a central route (area postrema signalling), and an effect on body weight in preclinical models and early clinical studies.

Origin: developed by Novo Nordisk specifically for the combination with semaglutide. Cagrilintide as a monotherapy is not authorised as a medicine — it remains in the trial phase.

Characteristics of the Sema+Cagri 4mg+4mg blend

Total in the pen: 8 mg of peptides, pre-dissolved in a fixed 1:1 ratio. Cold chain 2–8°C. COA per batch with separate HPLC peaks for both peptides.

Mechanism of synergy — what the literature says

The CagriSema hypothesis rests on the complementarity of two parallel metabolic signalling pathways.

The GLP-1 axis (semaglutide). Activation of GLP-1R in pancreatic β cells increases cAMP and potentiates insulin secretion in response to glucose. In parallel, GLP-1R in the arcuate nucleus of the hypothalamus mediates satiety signalling; suppression of glucagon in α cells closes the loop of postprandial glycaemic control.

The amylin/calcitonin axis (cagrilintide). Activation of AMY3R and CTR acts in parallel: slowed gastric emptying prolongs satiety, while area postrema signalling modulates appetite via a route independent of the hypothalamic GLP-1 pathways.

CagriSema data: phase II reported body weight reduction of around 17% (in the context of Lau et al. 2024, NEJM; earlier phase 1b/2a data — Enebo, Lau 2021, Lancet). Phase III REDEFINE 1–4 is being conducted in the setting of obesity and T2D.

Methodological limitation. The clinical CagriSema data concern the injectable form in a controlled Novo Nordisk protocol in humans. There is no randomised evidence of synergy for the blend in the RUO pen format.

Sema+Cagri PEN RUO vs clinical CagriSema vs authorised medicines

The identity (or kinship) of the active substances does not remove the distinction between regulatory frames — the RUO pen, the peptide in a clinical protocol and the authorised medicine are three separate product categories.

Applications in scientific research

Sema+Cagri 4mg+4mg PEN as an RUO reagent finds use in several research directions.

Pharmacology of the GLP-1/amylin axis. Receptor-activity assays of two classes in parallel (GLP-1R + AMY3R/CTR) in cell cultures with cAMP and β-arrestin reporters — the blend in the pen makes it possible to compare the signalling of both axes in a single experiment.

Animal models of insulin resistance and obesity. DIO mice, ob/ob, db/db, Zucker rats. Endpoints: body weight, composition (DEXA, NMR), OGTT/ITT, HOMA-IR, lipid profile.

Comparative analyses of anti-obesity classes. Monoagonists (semaglutide, liraglutide), dual agonists (tirzepatide — GLP-1R/GIPR), GLP-1 + amylin combinations (CagriSema) and tri-agonists (retatrutide — GLP-1R/GIPR/GCGR).

Experiments on peptide combinations in solution. The stability of two acylated peptides in a single buffer, degradation profile, HPLC compatibility.

One Peptides quality specification

Each Sema+Cagri pen undergoes an analytical control process.

• HPLC ≥98% for each peptide — two separate peaks in the respective retention windows.
• MS confirmation — confirmation of the identity of both peptides (~4113 Da semaglutide, ~4500 Da cagrilintide).
• COA per batch with separate results for both peptides, the synthesis date and the batch number.
• Cold chain 2–8°C — a monitored refrigerated chain.
• Batch traceability — the batch number in three places: the pen label, the invoice and the COA.

Working with the pre-dissolved PEN in a laboratory protocol

A pre-dissolved pen — no reconstitution. Total concentration: 8 mg of peptides pre-dissolved in solution, in a fixed 1:1 ratio (4 mg semaglutide + 4 mg cagrilintide). The volume configuration may vary by batch — see the COA for details.

Drawing the solution. Under laboratory conditions, the solution is drawn with a syringe or a dedicated pen applicator, in line with the research team’s protocol. The solution should be clear — turbidity or sediment disqualifies the batch from further work.

Fixed 1:1 ratio — an experimental limitation. The Sema+Cagri PEN does not allow independent control of the semaglutide vs cagrilintide concentration. Every draw contains the two peptides in the ratio set by the formulation. Experiments requiring a variable ratio need separate monotherapy reagents.

Solution stability. After first opening, the pen typically retains activity for 14–28 days at 2–8°C (a conservative assumption for a blend of two acylated peptides in a single buffer). Longer storage requires assessment of HPLC drift for each of the peaks. Avoid freeze–thaw cycles.

For volume/peptide-mass calculations, teams use standard peptide calculators — accounting for the total mass of 8 mg.

Regulatory status and WADA

This product (Sema+Cagri 4mg+4mg PEN). Status: Research Use Only in the EU chemical-reagent trade. Label: “For research use only. Not for human use”. No authorisation as a medicine.

Semaglutide as a monotherapy medicine. Authorised — Ozempic, Wegovy, Rybelsus. Prescription only, under EMA/FDA oversight.

Cagrilintide as a monotherapy. Not authorised — in Novo Nordisk’s clinical-trial phase.

CagriSema (the combination). Not authorised — phase III, the REDEFINE 1–4 programme.

WADA. Peptides of the GLP-1 class and amylin analogues are not directly listed on the current Prohibited List as a separate category. Researchers should verify the current WADA list themselves with regard to general clauses.

FAQ

Is Sema+Cagri 4mg+4mg PEN the same as CagriSema (the Novo Nordisk medicine)?

No. CagriSema is the name of Novo Nordisk’s clinical programme for the semaglutide + cagrilintide combination, in phase III trials — without authorisation as a medicine. Sema+Cagri 4mg+4mg PEN in the One Peptides catalogue is an RUO research reagent containing the same two peptides in a 1:1 laboratory blend. Two separate regulatory frames and two separate intended uses.

How does the 4mg+4mg variant differ from the Sema+Cagri PEN 2mg+2mg?

Both forms are pre-dissolved RUO pens with a fixed 1:1 ratio — the difference is the peptide content. The 4mg+4mg variant has double the content (8 mg total versus 4 mg in the 2mg+2mg variant), which provides a larger pool of material for experimental series and longer protocols. The mechanism and the way of working are the same.

Can I control the semaglutide and cagrilintide concentrations separately?

No. The pen contains a blend in a fixed 1:1 ratio (4 mg + 4 mg). Every draw of the solution yields both peptides in the same ratio. Protocols requiring a variable ratio need separate monotherapy reagents.

Is there synergy between the mechanisms of semaglutide and cagrilintide?

The synergy hypothesis rests on the complementarity of two parallel metabolic signalling axes. Phase II CagriSema data reported body weight reduction of around 17%. The data concern the injectable form in a controlled clinical protocol by Novo Nordisk — there is no randomised evidence of synergy for the blend in the RUO pen format.

How long does the pen retain activity after first opening?

Conservatively: 14–28 days at 2–8°C for a blend of two acylated peptides in a single buffer. The exact time depends on storage conditions and is verified by assessing HPLC drift for each of the two peaks.

Is CagriSema on the WADA list?

Neither semaglutide nor cagrilintide is directly listed as a separate item on the current List. General clauses concerning substances with a related mechanism require independent verification of the current WADA list.

Bibliography

1. Wilding JPH et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP-1)
2. Lau J et al. (2015). Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide
3. Frias JP et al. (2021). Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2)
4. Marso SP et al. (2016). Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6)
5. Enebo LB et al. (2021). 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
6. Lau DCW et al. (2021). Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial

RUO disclaimer

Sema+Cagri 4mg+4mg PEN is a chemical reagent for research applications (Research Use Only). The product is not a medicine, a dietary supplement or a foodstuff. It is not intended for the diagnosis, treatment or prevention of disease in humans or animals. It is not subject to pharmaceutical regulation. CagriSema — the combination of semaglutide and cagrilintide — remains in phase III clinical trials at Novo Nordisk and is not authorised as a medicine in the EU and the USA. Cagrilintide as a monotherapy is not authorised. Semaglutide as a monotherapy is authorised in the form of Ozempic, Wegovy and Rybelsus and is available on prescription only, under medical supervision.