Section 01
What it's used for
Phase 3 Trial for Weight Loss
The Phase 3 REDEFINE program is testing cagrilintide plus semaglutide 2.4 mg (CagriSema) for weight loss. A Phase 2 trial found 15.6% weight loss at 32 weeks, but only in people with type 2 diabetes, not general obesity.
▸Clinical wording
The Phase 3 REDEFINE program is evaluating cagrilintide combined with semaglutide 2.4 mg (CagriSema) for weight management. In an earlier Phase 2 trial, co-administered cagrilintide and semaglutide 2.4 mg produced 15.6% weight loss at 32 weeks, but that trial enrolled people with type 2 diabetes, not a general obesity population. Weight-loss results in people with obesity without diabetes come from the ongoing Phase 3 REDEFINE program rather than this figure.
Phase 2: Weight Loss Alone
In a Phase 2 clinical trial, cagrilintide used by itself, without semaglutide, produced about 10% weight loss in participants, showing that it works as a treatment on its own, not just in combination with other drugs.
▸Clinical wording
Phase 2 data showed ~10% weight loss with cagrilintide alone, establishing independent efficacy.
Studied for Blood Sugar Control
Cagrilintide is being studied, in combination with the drug semaglutide, for its effect on blood sugar control, known medically as glycemic control, in people living with type 2 diabetes, a condition of chronically high blood sugar.
▸Clinical wording
Being studied for glycemic control in combination with semaglutide.
Section 02
Mechanism of Action
Turning on a separate fullness receptor
- The peptide activates the amylin receptor, built from a calcitonin receptor plus helper proteins.
- This receptor complex is distinct from the one targeted by GLP-1 drugs.
- Its fullness signal runs mainly through two centres in the brainstem.
▸Clinical wording
Amylin Receptor Complex Activation
Cagrilintide activates the amylin receptor — a heterodimer of the calcitonin receptor (CTR) with receptor activity-modifying proteins (RAMPs, primarily RAMP1-3). This receptor complex is distinct from GLP-1R, providing complementary satiety signaling primarily through the area postrema and nucleus tractus solitarius in the brainstem.
Two different fullness routes in the brain
- GLP-1 acts mainly on appetite centres in the hypothalamus.
- Amylin acts instead on fullness circuits in the brainstem, a fundamentally different neural route.
- Separate routes explain the additive weight loss reported for the two-drug combination.
▸Clinical wording
Satiety Through Distinct Pathways
While GLP-1 acts primarily on hypothalamic appetite centers, amylin acts on brainstem satiety circuits — a fundamentally different neural pathway. This explains the additive weight loss observed with CagriSema (cagrilintide + semaglutide) combination.
Section 03
Biological Pathways
- Amylin receptor complex activationCagrilintide activates the amylin receptor, a heterodimer of the calcitonin receptor (CTR) with RAMP1-3, coupled to cAMP signaling in area postrema neurons; this receptor complex is distinct from GLP-1R.
- Brainstem NTS satiety integrationArea postrema and nucleus tractus solitarius neurons integrate amylin receptor signaling with vagal afferent input, activating ERK1/2 in satiety-center neurons, complementing GLP-1R action.
- Vagal gastric emptying delayAmylin receptor activation drives vagal afferent activity that delays gastric emptying, a brainstem-based satiety mechanism distinct from the hypothalamic appetite pathways that GLP-1 engages primarily.
- Additive action with semaglutideBecause amylin signals through brainstem circuits distinct from GLP-1's hypothalamic appetite pathway, combining cagrilintide with semaglutide (CagriSema) produces additive weight loss in this combination.
Section 04
Dosage Information
Modified amylin analog with acylation for albumin binding| Route / system | Context | Range studied | Limitation |
|---|---|---|---|
| Subcutaneous — with semaglutide | Two phase 3 trials of the fixed combination | 2.4 mg cagrilintide plus 2.4 mg semaglutide weekly, 68 weeks. Weight −20.4% in 2108 adults, −13.7% in 904 with type 2 diabetes. | Placebo lost 3.0% and 3.4% in the same trials. That 20% belongs to two drugs together, not to cagrilintide, and no regulator has approved the pair. |
| Subcutaneous — cagrilintide alone | Comparator arm of a phase 3 trial, 68 weeks | 2.4 mg once weekly in 302 adults, the same dose as in the combination. Weight −11.5% at week 68, against −14.9% for semaglutide alone. | Placebo lost 3.0%. Cagrilintide alone was the weakest active arm in its own trial: a reference point, not a candidate — nobody has filed to approve it. |
| Subcutaneous — dose-finding | Phase 2 in overweight and obesity, 26 weeks | 0.3, 0.6, 1.2, 2.4 and 4.5 mg weekly in 706 adults: weight −6.0% at the lowest dose to −10.8% at the highest. | Placebo lost 3.0% and daily liraglutide 3.0 mg 9.0%. The best dose, 4.5 mg, never went to phase 3, which uses only 2.4 mg — so it has no long-term data. |
| Subcutaneous — self-administration | Step-up schedule circulating outside any trial | 0.25 mg weekly, then 0.5, 1.0 and 1.7 mg in four-week steps, reaching 2.4 mg at week 17 — 27–34 µg/kg at the top for 70–90 kg. | The schedule is copied from the trials, the material is not: cagrilintide is approved nowhere, vials carry no verified content, nobody watches the steps. |
Results
Syringe Fill Level (100u syringe)
Set positive values for: Recommended dose per kg.
Research Use Only. This information is for educational and research purposes only. Not intended for medical advice or self-medication.
Section 05
Protocols
No protocols featuring this peptide yet. Browse All Protocols
Section 06
Stability & Storage
Storing the product
Cagrilintide is an investigational compound intended for once-weekly subcutaneous injection. The C18 fatty acid acylation binds albumin in the bloodstream, extending its half-life. Investigational supply is kept at 2-8°C.
After opening
Once in use, the product continues to be kept refrigerated at 2-8°C, consistent with storage of the unopened supply. Specific in-use shelf life depends on the manufacturer's formulation and packaging, since this remains an investigational compound not yet standardised for consumer use. The albumin-binding fatty acid chain is what supports the extended half-life between doses.
Section 07
Side Effects & Precautions
GI effects (nausea 20-30%, vomiting, diarrhea) similar to other incretin-based therapies. Injection site reactions. The combination with semaglutide shows GI effects comparable to semaglutide alone, suggesting amylin agonism does not substantially add to GI burden.
Section 08
Regulatory Status
Novo Nordisk is instead seeking approval for a fixed-dose combination with semaglutide, CagriSema, and Phase 3 results for that combination against Eli Lilly's tirzepatide have been mixed.
FDA / United States
CagriSema's approval is pending
Novo Nordisk submitted a New Drug Application for once-weekly CagriSema (cagrilintide 2.4 mg with semaglutide 2.4 mg) on December 18, 2025, based on the REDEFINE 1 trial; a US decision is expected around the fourth quarter of 2026.
Clinical trials
Phase 3 REDEFINE results were mixed
REDEFINE 1 reported 22.7% average weight loss for CagriSema; REDEFINE 2 studied it in people with type 2 diabetes; in REDEFINE 4, CagriSema did not meet its non-inferiority goal against tirzepatide, losing on weight (20.2% vs 23.6% at 84 weeks).
Compounding
Not a legal ingredient on its own
Cagrilintide has never been approved as a standalone drug by any regulator, so it is not on the FDA's 503A bulk substances list; outside a registered clinical trial, any cagrilintide product on the market is an unapproved new drug.
WADA
Not on the Prohibited List
As an amylin-receptor agonist, cagrilintide is absent from both the S2 (peptide hormones) and S4 (hormone and metabolic modulators) sections of the 2026 list, and from the 2026 Monitoring Program, which tracks only semaglutide and tirzepatide markers.
Cagrilintide's own regulatory status depends entirely on what happens to CagriSema's pending applications — a positive Phase 3 result is not the same as an approval, and «research use only» cagrilintide sold online is not a legal substitute for either.
Section 09
Research Studies
- [1]Development of Cagrilintide, a Long-Acting Amylin AnalogueKruse T, Hansen JL, Dahl K, et al. · Journal of Medicinal Chemistry · 2021
- [2]AM833 Is a Novel Agonist of Calcitonin Family G Protein-Coupled Receptors: Pharmacological Comparison with Six Selective and Nonselective AgonistsFletcher MM, Keov P, Truong TT, et al. · Journal of Pharmacology and Experimental Therapeutics · 2021
- [3]A structural basis for amylin receptor phenotypeCao J, Belousoff MJ, Liang YL, et al. · Science · 2022
- [4]Amylin: Pharmacology, Physiology, and Clinical PotentialHay DL, Chen S, Lutz TA, Parkes DG, Roth JD · Pharmacological Reviews · 2015
- [5]Amylin brain circuitryBoccia L, Gamakharia S, Coester B, et al. · Peptides · 2020
- [6]A cross-species atlas of the dorsal vagal complex reveals neural mediators of the effects of cagrilintide on energy balanceLudwig MQ, Coester B, Gordian D, et al. · Nature Metabolism · 2026
- [7]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 trialLau DCW, Erichsen L, Francisco AM, et al. · The Lancet · 2021
- [8]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 trialEnebo LB, Berthelsen KK, Kankam M, et al. · The Lancet · 2021
- [9]Coadministered Cagrilintide and Semaglutide in Adults with Overweight or ObesityGarvey WT, Blüher M, Osorto Contreras CK, et al. · New England Journal of Medicine · 2025
Section 10
Frequently Asked Questions
Yes, but more weakly than the combination. In the head-to-head phase 3 arm, cagrilintide alone at 2.4 mg produced 11.5% weight loss over 68 weeks against 14.9% for semaglutide alone and 20.4% for the two combined; placebo lost 3.0%. It works through its own receptor pathway, but by itself it was the weakest active treatment tested in that trial.
Cagrilintide is a long-acting analog of amylin, a hormone normally co-released with insulin, and it acts through the amylin receptor — the calcitonin receptor paired with a RAMP protein — mainly on brainstem satiety circuits (the area postrema and nucleus tractus solitarius). Semaglutide is a GLP-1 analog acting mostly on hypothalamic appetite centres, a different receptor in a different part of the brain, which is why dosing the two together (CagriSema) produced additive weight loss in trials.
Reported effects are GI ones typical of incretin-based therapies — nausea in 20-30% of patients, plus vomiting and diarrhoea — along with injection-site reactions. In the combination trials, GI side effects with cagrilintide plus semaglutide were comparable to semaglutide alone, suggesting the amylin component doesn't add much extra GI burden on top of what semaglutide already causes.
Phase 3 trials use 2.4 mg once weekly, reached by gradual titration. An earlier phase 2 dose-finding trial tested 0.3 to 4.5 mg weekly, with weight loss ranging from 6.0% at the lowest dose to 10.8% at the highest — but that top dose was never carried into phase 3, which uses only 2.4 mg, so it has no long-term safety data. A step-up schedule circulating outside trials mimics that titration, but on unapproved, unverified material.
No. It is an investigational compound still in Phase 3 trials (the REDEFINE program), not approved by any regulatory authority. Novo Nordisk has said it plans regulatory submissions based on the Phase 3 data, but no approved product containing cagrilintide exists yet.
The available trial record covers cagrilintide combined with semaglutide (CagriSema) specifically. It does not include any published study combining cagrilintide with tirzepatide or retatrutide, so there is no trial evidence for those particular combinations.
As an investigational compound it is kept refrigerated at 2-8°C, both before and during use; the fatty acid chain that extends its action in the body doesn't change its storage needs. Specific in-use shelf life depends on the manufacturer's formulation, since it isn't yet standardised for consumer use.