Cagrilintide

NNC0174-0833, AM833; CagriSema = cagrilintide 2.4 mg + semaglutide 2.4 mg fixed-dose combination

Metabolic & weight

Awaiting medical reviewEN ES DE FR PT ZH+ Follow for updates

Note on this profile. Cagrilintide is an investigational medicine; CagriSema has completed Phase 3 trials and was submitted for regulatory approval in 2025–2026 but is not yet approved †. Neither is a research chemical with established community dosing. Anything sold under these names outside a clinical trial is unverified.

Summary

Class: Long-acting amylin analogue; 37-amino-acid synthetic peptide based on human amylin with stabilising substitutions and a C20 fatty-diacid side chain; acts at amylin receptors and calcitonin receptors (a "dual amylin and calcitonin receptor agonist", DACRA)
Mechanism: Mimics amylin, the hormone co-released with insulin, to increase fullness, slow gastric emptying and reduce food intake through brainstem and hypothalamic pathways that are distinct from GLP-1 — which is why the two combine well
Routes studied: Subcutaneous once-weekly (alone and co-administered or co-formulated with semaglutide)
Dose range reported: Phase 2 (cagrilintide alone): 0.3, 0.6, 1.2, 2.4 and 4.5 mg weekly after escalation. CagriSema Phase 3: escalation over 16 weeks to cagrilintide 2.4 mg + semaglutide 2.4 mg weekly. No approved dose
Half-life: ~7–8 days, supporting weekly dosing †
Storage: Trial product is a refrigerated solution (CagriSema is a single co-formulated pen). Grey-market lyophilised product: no public stability data
Regulatory status: Not approved anywhere. CagriSema regulatory submissions filed in the US and EU in 2025–2026 †; cagrilintide alone remains in trials

Doses are as reported in studies or by the community — never recommendations.

1What it is

Amylin is a natural hormone made by the same pancreatic beta cells that make insulin and released with it after meals. It tells the brain the meal is sufficient, slows the stomach and suppresses glucagon. Native amylin is unstable and clumps into fibrils (the amyloid deposits seen in type 2 diabetes), so it cannot be used as a drug; pramlintide (Symlin), a short-acting analogue approved in 2005 as an add-on to insulin, is injected with each meal.

Cagrilintide is Novo Nordisk's long-acting amylin analogue: the sequence was modified to prevent fibril formation and a fatty-diacid side chain was added for albumin binding, allowing once-weekly injection. It is synthetic. Because amylin and GLP-1 act on different brain circuits, Novo developed it mainly as a partner for semaglutide; the co-formulation is called CagriSema and is the company's intended successor to Wegovy. Cagrilintide alone is also being studied in people who do not tolerate GLP-1 drugs.

2How it's thought to work

Brainstem (area postrema). amylin receptors here signal satiety; activation reduces meal size and food intake. The area postrema is also where GLP-1 drugs act in part, but through separate receptors.

Hypothalamus and reward areas. amylin signalling appears to enhance leptin sensitivity and reduce food reward, which may help with the plateau that occurs on GLP-1 drugs alone.

Stomach and glucagon. slows gastric emptying and suppresses post-meal glucagon.

Calcitonin receptor activity. cagrilintide also activates the calcitonin receptor, which may contribute to weight effects and raises a theoretical question about bone and calcium effects not seen so far.

Complementarity with GLP-1. in Phase 1b, the combination produced more weight loss than either alone, consistent with additive mechanisms.

The amylin receptor is a calcitonin receptor paired with a RAMP partner protein. Activating it signals fullness through the brainstem and slows stomach emptying.Schematic — not to scale

3What the research shows

Graded A (Phase 2)

Cagrilintide alone

A 26-week dose-finding (n=706, overweight/obesity without diabetes) showed mean weight loss of 6.0–10.8% across doses 0.3–4.5 mg vs 3.0% with placebo and 9.0% with liraglutide 3.0 mg (Lau 2021, Lancet). Weight was still declining at 26 weeks. [1]

CagriSema Phase 1b and Phase 2

A 20-week Phase 1b study showed the combination produced ~17% weight loss vs ~10% for semaglutide alone over the same short period (Enebo 2021, Lancet). A 32-week Phase 2 trial in type 2 diabetes showed −15.6% weight with CagriSema vs −5.1% semaglutide and −8.1% cagrilintide alone, with HbA1c reduction of about 2.2 percentage points (Frias 2023, Lancet). [2][3]

Graded A (2025)

CagriSema Phase 3

REDEFINE 1 (n≈3,417, obesity without diabetes, 68 weeks): mean weight change −20.4% with CagriSema vs −14.9% semaglutide alone, −11.8% cagrilintide alone and −3.0% placebo in the treatment-policy analysis; ~22.7% among those adhering to treatment (Garvey 2025, NEJM). REDEFINE 2 (type 2 diabetes): −13.7% vs −3.4% placebo. The results were below the ~25% the sponsor had projected but still exceed semaglutide. REDEFINE 4 (head-to-head vs tirzepatide) and a cardiovascular outcomes trial (REDEFINE 3) are ongoing or reading out †. [4]

Glucose and cardiometabolic markers

Improvements in HbA1c, waist circumference, blood pressure and lipids across trials, broadly in proportion to weight loss.

Community use

No data; grey-market product cannot be assumed to be cagrilintide.

4Reported side effects and interactions

Literature-reported

Common (literature). nausea (the most frequent), vomiting, constipation, diarrhoea, decreased appetite, injection-site reactions, fatigue. In REDEFINE 1 gastrointestinal events were more common with CagriSema than semaglutide alone during escalation but were mostly mild to moderate and transient; discontinuation for adverse events was around 6%.

Of specific note. in the Phase 2 monotherapy trial, cagrilintide caused less nausea than liraglutide 3.0 mg at comparable weight loss, which supports its use in people intolerant of GLP-1 drugs. Heart rate changes were smaller than with GLP-1 .

Class-level and theoretical. gallbladder disease and pancreatitis as with any rapid weight loss; the GLP-1 component of CagriSema carries semaglutide's warnings (thyroid C-cell tumours in rodents, retinopathy signal, delayed gastric emptying); amylin analogues can cause hypoglycaemia when combined with insulin (pramlintide carries a boxed warning for this); calcitonin-receptor activity raises a theoretical bone/calcium question not borne out in data so far.

Muscle mass. body-composition data from the REDEFINE programme are limited; lean-mass loss alongside fat is expected.

Grey-market product risks. cagrilintide has never been commercially manufactured; vials sold online are of unknown identity and purity. Community "CagriSema" is usually two separate vials dosed together, which doubles the opportunity for milligram-level dosing errors.

Interactions. additive hypoglycaemia with insulin or sulfonylureas; slowed absorption of oral medicines; not for use in pregnancy. Full interaction data not yet published.

Markers researchers commonly monitor

Marker	Why it's watched
Body weight, waist circumference and body composition	primary trial endpoints; lean-mass tracking matters at this magnitude of loss.
HbA1c and fasting glucose	hypoglycaemia risk if combined with insulin or sulfonylureas, particularly given the amylin component.
Creatinine/eGFR and electrolytes	dehydration from GI effects.
Lipase/amylase	only with symptoms suggestive of pancreatitis.
Calcium and bone markers	a theoretical watch item from calcitonin-receptor activity; not routinely measured in trials.
Heart rate and blood pressure	smaller heart-rate effect than GLP-1 agonists; blood pressure typically falls.
Lipids and liver enzymes	generally improve.

Free for everyone. Safety information is never behind a paywall.

5Reconstitution and handling

No approved product exists. grey-market vials, if encountered, need the same milligram-level care as semaglutide: small volumes, high concentrations, easy ten-fold errors — and if combined with semaglutide, two separate calculations. Use the calculator and double-check units for each.

Open in calculator, pre-loaded →

6Commonly studied alongside

Semaglutide (the CagriSema combination is the primary development path); liraglutide (comparator in Phase 2); tirzepatide (comparator in REDEFINE 4). Novo is also studying cagrilintide with its next-generation agents (amycretin is a separate single-molecule GLP-1/amylin agonist, not a combination).

Informational cross-links. Not stack recommendations.

7Regulatory status by region

Region	Status (checked —)
United States	Investigational; not FDA-approved. CagriSema submission filed †
European Union	Investigational; CagriSema submission to EMA filed †
United Kingdom	Investigational; not licensed
Australia	Investigational; not approved
South Africa	Investigational; not registered
Sport (WADA)	Not specifically listed; as a non-approved substance falls under S0 †

8Open questions

Why REDEFINE 1 fell short of the weight loss projected from Phase 2, and whether flexible dosing protocols explain it.
How CagriSema compares with tirzepatide (REDEFINE 4) and whether amylin agonism preserves lean mass better than incretin drugs alone.
Long-term safety of chronic amylin/calcitonin receptor activation, including bone.
Whether cagrilintide alone becomes an option for people who cannot tolerate GLP-1 drugs.

9References

1Lau 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. Lancet. PubMed · DOI
2Enebo 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. Lancet. PubMed · DOI
3Frias JP et al. (2023). 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. PubMed · DOI
4Garvey WT et al. (2025). Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1). N Engl J Med. PubMed · DOI
5Kruse T et al. (2021). Development of cagrilintide, a long-acting amylin analogue. J Med Chem. PubMed · DOI
6Hay DL et al. (2015). Amylin: pharmacology, physiology, and clinical potential. Pharmacol Rev. PubMed · DOI
7Novo Nordisk (2025). REDEFINE 2 topline results announcement — press release, to be replaced with the peer-reviewed publication. PubMed

References are being resolved to PubMed/DOI identifiers; links search PubMed for the citation until then.

† Being confirmed by our reviewers against current sources.

10Community

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Self-reported side effects Phase 2

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11Page history

25 Oct 2026Profile published — awaiting medical review

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