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Weight management

CagriSema (Cagri + Sema)

The fixed combination of cagrilintide and semaglutide, two different satiety axes in one vial, with strong phase 3 data.

3 min read 14 sources

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CagriSema vial with white powder and the black TPD label on a white podium with a glowing light blue ring, next to two different blue 3D peptide chains in a bright lab
Combination in phase 3 · not approvedLab tested in the shop

Summary

At a glance

Sources checked on 26 Oct 2026

Body weight in REDEFINE 1
-20.4 %

after 68 weeks, all participants (placebo -3.0%)1

When taken as planned
-22.7 %

Semaglutide alone -16.1%, cagrilintide alone -11.8%, according to the manufacturer2

HbA1c in type 2 diabetes
-2.2 percentage points

Phase 2 after 32 weeks (semaglutide alone -1.8, cagrilintide alone -0.9)6

Phase 3 in the registry
18 trials

on the combination, 10 of them completed, as of 26 Oct 202612

  • CagriSema is the fixed combination of cagrilintide (amylin analogue) and semaglutide (GLP-1 agonist). Both act on satiety, but through different receptors.911
  • In the phase 3 trial REDEFINE 1 body weight fell by 20.4 percent on average after 68 weeks, by 3.0 percent on placebo. When taken as planned it was 22.7 percent according to the manufacturer.12
  • The combination came out ahead of the single compounds: semaglutide alone 16.1 and cagrilintide alone 11.8 percent (same analysis, manufacturer data).2
  • In type 2 diabetes long-term blood sugar HbA1c fell along with weight. Gastrointestinal effects were the most common, mostly mild to moderate and temporary.361
  • The combination is not approved (as of October 2026). The registry lists 18 phase 3 trials, 10 of them completed. Everything here is the state of research, not a recommendation.1312
Profile

Updated May 2026

Class
Amylin analog + GLP-1 agonist
Use
Subcutaneous

weekly

Ratio
half each

5+5 in the 10mg vial

WADA
not specifically listed
Sizes
5 to 20 mg

3 sizes in the shop

Contents 15 sections
  1. At a glance
  2. What is CagriSema?
  3. How it works
  4. What you need
  5. Reconstitution
  6. Dosing
  7. Injection
  8. What the research shows
  9. Research status
  10. Side effects
  11. Storage
  12. Related compounds
  13. FAQ
  14. Glossary
  15. Sources

What is CagriSema?

CagriSema is the fixed combination of two compounds you also find individually in the lexicon: cagrilintide (an amylin analog) and semaglutide (a GLP-1 agonist). Both dampen appetite but via different routes, together giving a stronger effect than either alone.

Our 10mg vial holds half of each (5mg cagrilintide + 5mg semaglutide). Novo Nordisk develops the fixed combination clinically as CagriSema.

Comparison

One, two or three receptors

Which receptors each compound targets, as stated in the TPD lexicon. Tap a card to open its entry.

GLP-1 agonist Semaglutide Amylin Calcitonin GLP-1 1 of 3 receptors Amylin agonist, selective Eloralintide Amylin Calcitonin GLP-1 1 of 3 receptors Amylin analogue Cagrilintide Amylin Calcitonin GLP-1 2 of 3 receptors
Combination CagriSema (Cagri + Sema) Amylin Calcitonin GLP-1 3 of 3 receptors

Simplified: more receptors does not automatically mean better, each path also brings its own effects. 914

How it works

Semaglutide acts at the GLP-1 receptor (incretin axis), cagrilintide at the amylin receptor, a different satiety axis. Because they engage two different systems, their effects on satiety and appetite add up. That is the appeal of the combination.

Details on the individual mechanisms are in the lexicon entries for semaglutide and cagrilintide.

Where it acts

Three receptor families, several organs

Tap a point or a card. Colour = receptor, grey = effect seen in trials.

  1. Brain

    Satiety via nerve cells, cagrilintide via the brainstem (shown in animal models)10

    AmylinCalcitoninGLP-1
  2. Stomach

    Gastric emptying slowed11

    AmylinGLP-1
  3. Pancreas

    HbA1c fell by 2.2 percentage points in 32 weeks in type 2 diabetes6

    Observed in trials
  4. Body weight

    On average -20.4% after 68 weeks (placebo -3.0%)1

    Observed in trials

Known targets9

Compound CHEMBL4802169 + CHEMBL2108724: four described targets, type of action on each card.

Amylin receptor 1 (AMY1)
Gene
CALCR + RAMP1
UniProt
P30988, O60894
ChEMBL
CHEMBL2111189
Action
Cagrilintide: agonist, binding shown in structural data
Amylin receptor 3 (AMY3)
Gene
CALCR + RAMP3
UniProt
P30988, O60896
ChEMBL
CHEMBL2111190
Action
Cagrilintide: agonist, binding shown in structural data
Calcitonin receptor (CTR)
Gene
CALCR
UniProt
P30988
ChEMBL
CHEMBL1832
Action
Cagrilintide: agonist, binding shown in structural data
GLP-1 receptor
Gene
GLP1R
UniProt
P43220
ChEMBL
CHEMBL1784
Action
Semaglutide: agonist, mechanism according to ChEMBL
Glass cell with two glowing docking sites, a different blue 3D peptide chain docking at each, a light blue arc of light between them
Symbolic image.

What you need

Supplies

2 things, numbered as in the picture

Tick off what you already have. Vial and BAC water are our real shop photos at the same size.

CagriSema vial and bacteriostatic water at the same size with the black TPD label, next to two U-100 insulin syringes, two alcohol swabs and a sharps container with a blue lid

  1. CagriSema vial

    The CagriSema vial (lyophilized powder, contains both compounds).

    In the shop

  2. Water and supplies

    Bacteriostatic water, U-100 insulin syringes, alcohol swabs.

    In the shop

Reconstitution

Use the peptide calculator. Since both compounds are in the same vial, the calculator always shows the total of both compounds: 1mg in the calculator is 0.5mg cagrilintide plus 0.5mg semaglutide. A 10mg vial with 2ml water gives 5mg per ml. Just add the water to the vial and let it dissolve.

Step by step

Dissolving the powder

Four steps, the same for every vial size.

  1. 1Wipe the cap

    Clean the rubber stopper with an alcohol swab.

  2. 2Add BAC water

    Just add it, it does not matter if it hits the powder directly.

  3. 3Swirl or shake

    Until everything has dissolved, both are fine.

  4. 4Draw up

    With the U-100 insulin syringe.

Less water higher concentration fewer units on the syringe Example: 10 mg + 2 ml = 5 mg/ml

Dosing

Dosing

Dosing, titration and syringe

Loading the dosing information …

  • Getting started and stepping up, drawn as a staircase
  • Units on the U-100 syringe for every step
  • How long one vial lasts

Injection

The injection is subcutaneous, into the fat layer under the skin. Common spots are the abdomen (keep about two finger-widths clear of the navel), the front and the inner side of the thigh, or the back of the upper arm.

The short version:

Injection

Where and at what angle

Pick a spot or switch the angle. Subcutaneous means: into the fat layer, not the muscle.

Rotate the spot each time, never the same one twice in a row.

90°More fat under the skin

Rule of thumb: where there is more fat under the skin, insert straight at 90 degrees. In lean people with little fat, 45 degrees, so the needle stays in the fat layer. Simplified diagram.

  1. Clean the spot with an alcohol swab and let it dry

  2. Pinch up a small fold of skin

  3. Insert the needle: at 90 degrees where there is more fat under the skin, at 45 degrees in lean people with little fat

  4. Inject slowly, wait a moment, then withdraw

  5. Put the needle straight into the sharps container

Rotate the site each time so the tissue does not get irritated. Never the same spot twice in a row.

CagriSema is injected once a week.

What the research shows

The phase 3 study REDEFINE 1 (NEJM, 2025) compared CagriSema with the individual compounds and placebo in 3,417 adults with overweight or obesity: after 68 weeks weight fell by 20.4 percent on average with CagriSema, versus 3.0 percent on placebo. According to the manufacturer it was 14.9 percent with semaglutide alone and 11.5 percent with cagrilintide alone. When taken as planned the manufacturer reports 22.7 percent for CagriSema (16.1 and 11.8 percent for the single compounds). That is strong evidence that the combination beats each of the two compounds alone.

Study results

What the trials measured

Interactive: switch tabs, tap points, show or hide arms. Arms are named relative to each other, no dosing advice.

Body weight after 68 weeks2

Mean change in percent, 3,417 participants without diabetes

All participants2 Treatment policy analysis
Placebo -3.0%
Cagrilintide alone -11.5%
Semaglutide alone -14.9%
Combination (CagriSema) -20.4%
When taken as planned2 Trial product analysis
Placebo -2.3%
Cagrilintide alone -11.8%
Semaglutide alone -16.1%
Combination (CagriSema) -22.7%

Combination and placebo in the first group are also in the trial abstract (-20.4 and -3.0 percent). The values of the single compounds and the second analysis come from the manufacturer's announcement of 20 Dec 2024.

Body weight in further trials346

Mean change in percent per trial

REDEFINE 2, 68 weeks3 Overweight with type 2 diabetes
Placebo -3.4%
Combination (CagriSema) -13.7%
REDEFINE 5, 68 weeks4 East Asia, compared with semaglutide alone
Semaglutide alone -11.9%
Combination (CagriSema) -18.4%
Phase 2, 32 weeks6 Type 2 diabetes, three groups without placebo
Cagrilintide alone -8.1%
Semaglutide alone -5.1%
Combination (CagriSema) -15.6%

Values as stated in the trial abstracts. The trials differ in population and duration and are not directly comparable.

Long-term blood sugar HbA1c65

Change in percentage points

Phase 2, 32 weeks6 92 participants
Cagrilintide alone -0.90 pp
Semaglutide alone -1.80 pp
Combination (CagriSema) -2.20 pp
REIMAGINE 2, 68 weeks5 Main comparison with semaglutide alone
Semaglutide alone -1.75 pp
Combination (CagriSema) -1.91 pp

In REIMAGINE 2 the difference from semaglutide alone was small at 0.16 percentage points but statistically significant (analysis when taken as planned).

Stainless steel lab cart seen from below, carrying a frosted glass stomach model and a glass brain model, a bright lab in the background
Symbolic image.

Research status

Where the research stands

From the design of the amylin analogue to the large phase 3 programmes REDEFINE and REIMAGINE: registered trials of the combination with status, participants and results. As of 26 Oct 2026. 12

  1. Preclinical Design of cagrilintide, cell assays and animals
  2. Phase 1 9 trials, 7 completed
  3. Phase 2 5 trials, 5 completed
  4. Phase 3 18 trials, 10 completed
  5. Approval not yet
22,944 participants in phase 3 Planned figures for running trials The combination is not approved yet. Semaglutide alone has been approved since 2017, ChEMBL lists cagrilintide with phase 3 as the highest phase and no approval.12
Show all 23 phase 2 and 3 trials on a timelineHide timeline 15 completed 8 running 5 with results
Phase 2
Phase 3

Bar: start to primary endpoint (planned for running trials). Green = completed, blue = progress until 26 Oct 2026. Phase 1: 9 trials on safety and pharmacokinetics, not shown as bars.

Side effects

  • Mainly gastrointestinal: nausea, fullness, constipation or diarrhea, especially when dosing up.
  • A slow ease-in keeps this small.
  • See the individual entries for semaglutide and cagrilintide.

Tolerability

Gastrointestinal effects and side effects

Out of 100 participants per group, how many had the event over 68 weeks.

40 of 100 Placebo
80 of 100 Combination (CagriSema)
Event PlaceboCombination (CagriSema)
Gastrointestinal, REDEFINE 11 40%80%
Gastrointestinal, REDEFINE 23 34%73%
Side effects overall, REIMAGINE 25 71%87%

Gastrointestinal effects were nausea, vomiting, diarrhoea, constipation or abdominal pain, mostly mild to moderate and temporary according to the trials.135

Storage

Before mixing the powder is robust, normal room temperature (around 20 to 25 degrees) is fine, ideally kept in the dark. After mixing, keep in the fridge (2 to 8 degrees), do not freeze. It stays good there for at least 4 to 6 months with barely any loss of potency, in practice considerably longer. Swirl or shake to mix, both are fine.

Shelf life

How long it keeps

Undissolved (powder) Room temperature, around 20 to 25 degrees, dark

Robust, no fridge needed.

Dissolved (mixed) Fridge, 2 to 8 degrees, do not freeze

At least 4 to 6 months with barely any loss of potency.

  • Keep it dark
  • Dissolved: 2 to 8 degrees
  • Note the mixing date on the vial
Nine vials with white powder and blue caps in the door shelf of a bright fridge
Powder dark at room temperature, once dissolved into the fridge (2 to 8 degrees), stable there for at least 4 to 6 months. Symbolic image.

Related

Related compounds

Same receptors or blends with CagriSema (Cagri + Sema): all in the TPD lexicon.

CagriSema (Cagri + Sema)
Cagrilintide Component: cagrilintide alone Semaglutide Component: semaglutide alone Reta + Cagri Blend Contains cagrilintide plus retatrutide Eloralintide Also amylin, prefers AMY1 Tirzepatide Different path: GLP-1 and GIP Retatrutide Different path: three receptors

FAQ

Common questions about CagriSema (Cagri + Sema)

Short answers, each backed by the sources below.

Is CagriSema approved?

No, the combination is not approved (as of 26 October 2026). Semaglutide alone has been approved since 2017, ChEMBL lists cagrilintide with phase 3 as the highest phase. ClinicalTrials.gov lists 18 phase 3 trials of the combination, 10 of them completed.131412

What does the combination add over the single compounds?

In REDEFINE 1 the combination came out ahead after 68 weeks. For all participants: -20.4 percent versus -14.9 (semaglutide alone), -11.5 (cagrilintide alone) and -3.0 (placebo). When taken as planned: -22.7 versus -16.1, -11.8 and -2.3 percent. The values of the single compounds come from the manufacturer's announcement, the abstract only reports combination and placebo.12

Why two compounds in one vial?

Because they act on different receptors. Cagrilintide binds to amylin and calcitonin receptors, semaglutide to the GLP-1 receptor. In rats cagrilintide worked through specific nerve cells in the brainstem that semaglutide did not need. The effects on satiety and the stomach thus add up.91011

What do the trials show in type 2 diabetes?

In REDEFINE 2 weight fell by 13.7 percent after 68 weeks (placebo 3.4), 73.5 percent reached an HbA1c of 6.5 percent or below (placebo 15.9). In phase 2 HbA1c fell by 2.2 percentage points in 32 weeks. In REIMAGINE 2 the combination was slightly but significantly ahead of semaglutide alone on HbA1c.365

How long do the compounds stay in the body?

In the first study of the combination the half-life of cagrilintide was 159 to 195 hours, that of semaglutide 145 to 165 hours, so both about one week. Cagrilintide did not change semaglutide blood levels. That is why the trials give the combination once a week.7

Which side effects were seen?

Mainly gastrointestinal effects such as nausea, vomiting, diarrhoea or constipation: in REDEFINE 1 in 79.6 percent (placebo 39.9), in REDEFINE 2 in 72.5 percent (placebo 34.4). According to the trials they were mostly mild to moderate and passed.13

How did the combination do directly against semaglutide?

In REDEFINE 5 in Japan and Taiwan weight fell by 18.4 percent with the combination after 68 weeks, by 11.9 percent with semaglutide alone. Gastrointestinal effects were similarly common in both groups (53 versus 51 percent).4

Glossary

Terms explained briefly

Dotted words in the text open these explanations directly.

Agonist
A substance that binds to a receptor and activates it, like the body's own messenger.
Amylin
Hormone that the pancreas releases together with insulin. It slows gastric emptying and signals fullness to the brain. Cagrilintide is a long-acting analogue.
Calcitonin receptor
Receptor that forms the amylin receptors together with a helper protein (RAMP). Cagrilintide activates both forms.
GLP-1
Glucagon-like peptide 1: gut hormone that releases insulin, slows gastric emptying and signals fullness in the brain. Semaglutide acts through this receptor.
Half-life
Time after which only half of a substance is left in the blood. At about one week one dose a week keeps the level steady.
HbA1c
Long-term blood sugar: reflects average blood sugar over the past eight to twelve weeks.
Lyophilisate
Freeze-dried powder. Without water a peptide keeps much longer.
Placebo
Dummy preparation without active substance. Comparing against it shows what is due to the substance itself.
Receptor
Protein on the cell surface that a messenger docks onto. Only then does the cell respond.
Subcutaneous
Into the fat layer just under the skin.
Trial phases
Phase 1 tests tolerability in a few people, phase 2 looks for the dose, phase 3 confirms benefit and safety in thousands. After that, approval can be requested.
Two analyses
Treatment policy counts all participants, including those who stopped. The analysis when taken as planned calculates as if everyone had taken the drug as intended and is therefore usually somewhat stronger.

Evidence

Sources

Show all 14 sourcesHide sources 10 Studies1 Trial registry3 Database checked 26 Oct 2026

Studies

  1. Phase 3 trial REDEFINE 1 in overweight without diabetes

    Garvey et al., New England Journal of Medicine, 2025

    DOI 10.1056/NEJMoa2502081 PMID 40544433 NCT05567796
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  2. Phase 3 trial REDEFINE 2 with type 2 diabetes

    Davies et al., New England Journal of Medicine, 2025

    DOI 10.1056/NEJMoa2502082 PMID 40544432 NCT05394519
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  3. Phase 3 trial REDEFINE 5 in East Asia

    Yamauchi et al., The Lancet Diabetes & Endocrinology, 2026

    DOI 10.1016/S2213-8587(25)00402-4 PMID 42009015 NCT05813925
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  4. Phase 3 trial REIMAGINE 2 in type 2 diabetes

    Buse et al., The Lancet Diabetes & Endocrinology, 2026

    DOI 10.1016/S2213-8587(26)00125-7 PMID 42251859 NCT06065540
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  5. Phase 2 trial in type 2 diabetes, combination versus single compounds

    Frias et al., The Lancet, 2023

    DOI 10.1016/S0140-6736(23)01163-7 PMID 37364590 NCT04982575
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  6. First study of the combination with half-lives (phase 1b)

    Enebo et al., The Lancet, 2021

    DOI 10.1016/S0140-6736(21)00845-X PMID 33894838 NCT03600480
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  7. Development of the long-acting amylin analogue cagrilintide

    Kruse et al., Journal of Medicinal Chemistry, 2021

    DOI 10.1021/acs.jmedchem.1c00565 PMID 34288673
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  8. Structures of binding to amylin and calcitonin receptors

    Cao et al., Nature Communications, 2025

    DOI 10.1038/s41467-025-58680-y PMID 40204768
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  9. Site of action in the brainstem (rat, mouse, macaque)

    Ludwig et al., Nature Metabolism, 2026

    DOI 10.1038/s42255-026-01539-3 PMID 42260119
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed
  10. Review of amylin and amylin analogues

    Alhazmi und le Roux, Diabetes, Obesity and Metabolism, 2026

    DOI 10.1111/dom.71074 PMID 42452898
    Checked 26 Oct 2026 via doi.org, Crossref, PubMed

Trial registry

  1. Trials on ClinicalTrials.gov

    ClinicalTrials.gov, U.S. National Library of Medicine

    Checked 26 Oct 2026 via ClinicalTrials.gov API v2

Database

  1. Company announcement on the results of REDEFINE 1

    Novo Nordisk, Unternehmensmitteilung vom 20.12.2024

    Checked 26 Oct 2026 via Website des Herstellers
  2. Cagrilintide in ChEMBL (highest phase 3)

    ChEMBL, EMBL-EBI (CHEMBL4802169)

    Checked 26 Oct 2026 via ChEMBL
  3. Semaglutide in ChEMBL (approved, target GLP-1 receptor)

    ChEMBL, EMBL-EBI (CHEMBL2108724)

    Checked 26 Oct 2026 via ChEMBL

In the shop

CagriSema (Cagri + Sema) in the catalog

Sizes, prices and shipping times are on the product page.

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