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Not a GLP-1 at all: a lipidated human-amylin analogue with six substitutions, designed to pair with semaglutide.
Also known as: NN9838 · AM833 · long-acting amylin analogue · DACRA
Part of the Metabolic & GLP-1 peptides cluster
Overview
Cagrilintide is an investigational 37-amino-acid analogue of the pancreatic hormone amylin (C194H312N54O59S2, ≈4,409 Da). Six substitutions stop it forming amyloid fibrils, and a C20 fatty diacid on the N-terminal lysine binds albumin for a half-life of 7–8 days. It activates amylin and calcitonin receptors — not the GLP-1 receptor — which is why it is being developed in combination with semaglutide as CagriSema: −20.4% body weight at 68 weeks in the phase 3 REDEFINE 1 trial.
Source & context
Biological / chemical source: Synthetic amylin analog
Primary research or clinical context: Investigational; studied alone and co-administered with semaglutide as CagriSema (phase 3 REDEFINE programme)
What cagrilintide is
Cagrilintide is a long-acting analogue of amylin, the 37-residue hormone that pancreatic β-cells release alongside insulin. It was developed by Novo Nordisk (codes NN9838, AM833) as a once-weekly injection and is best known as the “Cagri” half of CagriSema, its fixed combination with semaglutide. Chemically it is a 37-amino-acid peptide with a molecular formula of C194H312N54O59S2 and an average molecular weight of about 4,409 Da — the two sulfurs are the disulfide bridge between cysteines 2 and 7 that all amylin-family peptides carry. It does not act on the GLP-1 receptor at all.
Amylin biology in one paragraph
Amylin is co-secreted with insulin after meals and signals satiety through receptors in the area postrema and hypothalamus; it also slows gastric emptying and suppresses glucagon. Its receptors are unusual: the calcitonin receptor becomes an amylin receptor (AMY1, AMY2 or AMY3) when it pairs with one of three receptor-activity-modifying proteins (RAMPs). Native amylin's problem as a drug is that human amylin aggregates into amyloid fibrils — the same deposits found in the pancreas in type 2 diabetes — and lasts only minutes in plasma. Pramlintide, approved in 2005, solved the fibrillation problem with three proline substitutions but still needed injection before every meal.
Sequence and the six substitutions
In one-letter code: K-C-N-T-A-T-C-A-T-Q-R-L-A-E-F-L-R-H-S-S-N-N-F-G-P-I-L-P-P-T-N-V-G-S-N-T-P-NH2, with a C20 fatty diacid attached through a γ-glutamate to the N-terminal lysine's α-amine — unusually, the lipid is on the N-terminus rather than a lysine side chain. Compared with human amylin (KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY-NH2), six residues are changed: Glu14, Arg17, Pro25, Pro28, Pro29 and Pro37. The three prolines at 25, 28 and 29 are the pramlintide substitutions that block fibril formation; Glu14 and Arg17 improve solubility; Pro37 replaces the C-terminal tyrosine and contributes to the molecule's calcitonin-receptor activity. The structure-activity work is described in Kruse et al. (J Med Chem 2021).
| Position | Human amylin | Pramlintide | Cagrilintide |
|---|---|---|---|
| 14 | Asn | Asn | Glu |
| 17 | Val | Val | Arg |
| 25 | Ala | Pro | Pro |
| 28 | Ser | Pro | Pro |
| 29 | Ser | Pro | Pro |
| 37 | Tyr | Tyr | Pro |
| N-terminus | Free | Free | C20 diacid-γGlu |
| Half-life | Minutes | ≈ 48 min | ≈ 7–8 days |
Why the prolines matter
Residues 20–29 of human amylin form the β-strand that nucleates amyloid fibrils; that segment is why native amylin cannot be formulated as a stable solution. Proline cannot sit inside a β-sheet, so inserting prolines at 25, 28 and 29 (first done in pramlintide, which copies rat amylin at those positions) makes fibrillation thermodynamically unfavourable. Cagrilintide keeps those three prolines and adds Glu14 and Arg17, which further raise solubility at the concentrations needed for a once-weekly product. The result is a peptide stable enough to be co-formulated in the same pen as semaglutide.
Half-life and once-weekly dosing
The C20 fatty diacid on the N-terminus binds albumin the same way semaglutide's and tirzepatide's side chains do. In the phase 1b co-administration study (Enebo et al., Lancet 2021), cagrilintide's half-life was 159–195 hours across the 0.16–4.5 mg dose range, with peak concentrations at 24–72 hours after injection; semaglutide's half-life in the same participants was 145–165 hours. The two peptides did not affect each other's exposure, which is what allows them to be dosed together once a week without an interaction problem.
Cagrilintide alone: phase 2 results
In the phase 2 monotherapy trial (Lau et al., Lancet 2021; 706 adults, 26 weeks), once-weekly cagrilintide produced dose-dependent weight loss up to about 10.8% at 4.5 mg, versus about 3.0% with placebo and 9.0% with once-daily liraglutide 3.0 mg as an active comparator. Gastrointestinal adverse events were the most common, mostly mild to moderate, and less frequent than typically seen with GLP-1 agonists at comparable weight loss — one of the reasons amylin agonism is attractive as a partner mechanism.
CagriSema: cagrilintide plus semaglutide
Because amylin and GLP-1 reduce appetite through partly separate pathways, combining them was expected to be additive. REDEFINE 1 (Garvey et al., NEJM 2025; 3,417 adults with overweight or obesity, 68 weeks) tested cagrilintide 2.4 mg plus semaglutide 2.4 mg once weekly: mean weight change was −20.4% versus −3.0% with placebo, with each component alone producing smaller reductions. Gastrointestinal adverse events occurred in 79.6% of the combination group versus 39.9% on placebo, mainly transient and mild to moderate. REDEFINE 2 in type 2 diabetes reported in 2026. The CagriSema guide linked below covers the programme in detail.
Regulatory status
Cagrilintide is investigational. It is not approved as a monotherapy anywhere, and CagriSema had not received marketing authorisation as of September 2026; Novo Nordisk has said regulatory submissions would follow the REDEFINE phase 3 programme. As with every peptide on this site, products sold online as “cagrilintide” are unlicensed material of unverified content, and this profile is educational rather than guidance on obtaining or using them.
Sequence
One-letter sequence commonly cited for Cagrilintide (educational; isoforms and modifications may differ):
KCNTATCATQRLAEFLRHSSNNFGPILPPTNVGSNTP
Residues plotted ~100° apart around an α-helix — clustering of one color reveals an amphipathic face.
Structure & chemistry
Molecular identity & reference confidence
Source-supported reference
Reference values are taken from the cited molecular record or curated profile. A database match is not independent laboratory verification; modifications, counter-ions, and formulations can change the measured mass.
- Molecular form
- Human amylin (IAPP), 37 residues, with six substitutions
- Species
- Not established by this molecular identity audit
- Termini (N / C)
- Not specified / Amide
Average reference mass
Reference policy updated: 2026-10-05
- IUPHAR/BPS source snapshot · 2026-10-01
- PubChem molecular record · 2026-10-01
(C20 diacid-γGlu)-K-C-N-T-A-T-C-A-T-Q-R-L-A-E-F-L-R-H-S-S-N-N-F-G-P-I-L-P-P-T-N-V-G-S-N-T-P-NH2, with a Cys2–Cys7 disulfide bridge
- Molecular formula
- C194H312N54O59S2
- Average reference mass
- ≈ 4,409
- Plasma half-life
- ≈ 7–8 days (159–195 h across doses in the phase 1b study)
- Receptors
- Amylin receptors (AMY1–3: calcitonin receptor + RAMP1–3) and the calcitonin receptor itself — a dual amylin/calcitonin receptor agonist (DACRA). No GLP-1 receptor activity
- Backbone
- Human amylin (IAPP), 37 residues, with six substitutions
- Lipidation
- Eicosanedioic acid (C20 fatty diacid) → γ-glutamate → α-amine of the N-terminal lysine (Lys1) — the lipid is on the N-terminus, not a side chain
- C-terminus
- Amide
- Status
- Investigational (phase 3, as CagriSema with semaglutide); not approved as of September 2026
| Position | Native | Analog | Purpose |
|---|---|---|---|
| Asn14 → Glu | N | E | Solubility; reduces aggregation |
| Val17 → Arg | V | R | Solubility and receptor selectivity |
| Ala25 → Pro | A | P | Breaks the amyloid-forming β-strand (as in pramlintide) |
| Ser28 → Pro | S | P | Prevents fibrillation |
| Ser29 → Pro | S | P | Prevents fibrillation |
| Tyr37 → Pro | Y | P | C-terminal stability; contributes to calcitonin receptor activity |
| N-terminus (Lys1) | Free amine | C20 diacid-γGlu | Albumin binding → once-weekly half-life |
- PubChem CID: 171397054
- IUPHAR ligand: 13768
- DrugBank: DB18887
- CAS RN: 1415456-99-3
- UNII: AO43BIF1U8
Chemistry values: curated profile, IUPHAR/BPS Guide to Pharmacology · fetched 2026-10-01.
Clinical development snapshot
ClinicalTrials.gov lists 44 registered studies with “Cagrilintide” as an intervention (snapshot 2026-10-01). A registry footprint is not evidence of efficacy or approval.
| NCT | Title | Phase | Status | Updated |
|---|---|---|---|---|
| NCT05567796 | A Research Study to See How Well CagriSema Helps People With Excess Body Weight Lose Weight | Phase 3 | active not recruiting | 2026-09-30 |
| NCT07011667 | A Research Study to Look at How Well CagriSema Helps People Living With Obesity Lose Weight and Maintain Weigh | Phase 3 | active not recruiting | 2026-09-30 |
| NCT07253285 | A Research Study on How Well Cagrilintide and CagriSema Work in Children and Adolescents With Excess Body Weig | Phase 3 | recruiting | 2026-09-30 |
| NCT06323174 | A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Placebo in People Wi | Phase 3 | completed | 2026-09-30 |
| NCT07817251 | Research Study on How People With Type 2 Diabetes Tolerate Switching From Semaglutide to Cagrisema | Phase 3 | recruiting | 2026-09-30 |
| NCT07564414 | A Research Study to Look at How Two Different Doses of CagriSema and One Dose of Semaglutide Help People Livin | Phase 3 | recruiting | 2026-09-30 |
The incretin & metabolic co-agonist class at a glance
| Peptide | Receptors | Length | Mass (Da) | Half-life | Status |
|---|---|---|---|---|---|
| GLP-1 | GLP-1R | 30 aa | ≈ 3,297.6 | ≈ 1–2 min (DPP-4 cleavage + renal clearance) | Endogenous hormone — not a product |
| Liraglutide | GLP-1R | 31 aa | ≈ 3,751.2 | ≈ 13 h (once-daily dosing) | Approved: Victoza (2010, T2D), Saxenda (2014, weight) |
| Semaglutide | GLP-1R | 31 aa | ≈ 4,113.6 | ≈ 7 days (≈ 145–165 h in clinical PK studies) | Approved: Ozempic (2017, T2D), Rybelsus (2019, oral T2D), Wegovy (2021, weight) |
| Tirzepatide | GIPR + GLP-1R | 39 aa | ≈ 4,813.5 | ≈ 5 days (≈ 117 h) | Approved: Mounjaro (2022, T2D), Zepbound (2023, weight; 2024, obstructive sleep apnoea) |
| Retatrutide | GIPR + GLP-1R + GCGR | 39 aa | ≈ 4,731 | ≈ 6 days | Investigational (phase 3) |
| Cagrilintide (this page) | Amylin / calcitonin | 37 aa | ≈ 4,409 | ≈ 7–8 days (159–195 h across doses in the phase 1b study) | Investigational (phase 3, as CagriSema with semaglutide) |
| Survodutide | GCGR + GLP-1R | 29 aa | ≈ 4,232 | Supports once-weekly dosing (published population estimates are on the order of several days) | Investigational (phase 3: SYNCHRONIZE obesity programme; MASH programme) |
| Mazdutide | GCGR + GLP-1R | 34 aa | ≈ 4,476 | Supports once-weekly dosing (published estimates are on the order of several days) | Approved in China (NMPA): chronic weight management (27 June 2025) and type 2 diabetes (2025) |
| Amycretin | GLP-1R + amylin | — | — | Supports once-weekly subcutaneous dosing | Investigational (phase 2 results published 2025; later-phase trials under way) |
Verified from PubChem, IUPHAR and the primary discovery papers cited on each profile. Half-lives are approximate population means from published pharmacokinetics.
Cagrilintide — reconstitution calculator
Enter how much peptide is in the vial and how much diluent (e.g. bacteriostatic water) is added. The tool returns the resulting solution concentration — and, for any amount you type, the volume it corresponds to. This is educational arithmetic, not a dosing recommendation.
Reference form: Human amylin (IAPP), 37 residues, with six substitutionsAverage reference mass: 4,409 Da
Enter an amount to see the volume it corresponds to.
Educational concentration mathematics only. This tool does not recommend a dose, amount, or protocol, and nothing here is medical advice. Many peptides are not authorized by Health Canada for human use — see our reconstitution and bacteriostatic-water guides for context.
Change log
Dated observations from the data pipeline (registry flags, trial footprints, identifiers) and editorial reviews of this profile.
- Trials1 registered study added on ClinicalTrials.gov (now 44).
- EditorialProfile content reviewed and updated by the editorial team.
FAQ about Cagrilintide
What is Cagrilintide?+
Cagrilintide is an investigational 37-amino-acid analogue of the pancreatic hormone amylin (C194H312N54O59S2, ≈4,409 Da). Six substitutions stop it forming amyloid fibrils, and a C20 fatty diacid on the N-terminal lysine binds albumin for a half-life of 7–8 days. It activates amylin and calcitonin receptors — not the GLP-1 receptor — which is why it is being developed in combination with semaglutide as CagriSema: −20.4% body weight at 68 weeks in the phase 3 REDEFINE 1 trial.
What Canadian product status is recorded for Cagrilintide?+
Canadian product status for Cagrilintide has not been verified in this profile. No verified record here does not mean no authorization exists. Status depends on the product, formulation and use; consult Health Canada's product records.
What is the typical length of Cagrilintide?+
Cagrilintide is commonly described as approximately 37 amino acids (Amylin analog (dual amylin / calcitonin receptor agonist)).
What is cagrilintide?+
An investigational once-weekly analogue of the hormone amylin, developed by Novo Nordisk. It is a 37-amino-acid lipidated peptide that activates amylin and calcitonin receptors to reduce appetite, and it is the cagrilintide half of CagriSema.
Is cagrilintide a GLP-1?+
No. Cagrilintide is an amylin analogue and has no GLP-1 receptor activity. That is exactly why it is paired with semaglutide (a GLP-1 agonist): the two act through different receptors.
What is the sequence of cagrilintide?+
KCNTATCATQRLAEFLRHSSNNFGPILPPTNVGSNTP-NH2 with a Cys2–Cys7 disulfide and a C20 fatty diacid-γGlu on the N-terminal lysine. It differs from human amylin at positions 14, 17, 25, 28, 29 and 37.
What is cagrilintide's half-life?+
About 7–8 days (159–195 hours measured in the phase 1b study), which supports once-weekly injection.
What is CagriSema?+
A once-weekly co-formulation of cagrilintide 2.4 mg and semaglutide 2.4 mg. In the phase 3 REDEFINE 1 trial it produced −20.4% body weight at 68 weeks versus −3.0% with placebo. It is not yet approved.
Cagrilintide vs semaglutide — which is more effective?+
As monotherapies, semaglutide 2.4 mg (−14.9% in STEP 1 at 68 weeks) outperformed cagrilintide 4.5 mg (about −10.8% at 26 weeks); the trials are not directly comparable. The point of cagrilintide is that combining the two produced more weight loss than either alone.
Further reading
- Metabolic peptidesCagriSema Explained: Cagrilintide + Semaglutide, Mechanism and REDEFINE Trial ResultsCagriSema combines cagrilintide (a long-acting amylin analogue) with semaglutide (a GLP-1 agonist) in one weekly injection. This guide explains why two receptors beat one, what REDEFINE 1 showed (−20.4% at 68 weeks), how it compares with tirzepatide and retatrutide, and where approval stands.
- Clinical evidenceCagrilintide Dosage and Side Effects: What the Phase 2 and REDEFINE Trials Used and ReportedThe once-weekly doses cagrilintide was tested at (0.3–4.5 mg alone; 2.4 mg with semaglutide as CagriSema), how the trials escalated, the weight loss each arm produced, and the adverse events reported — gastrointestinal effects and injection-site reactions above all. Descriptive, not prescriptive.
- Metabolic peptidesGLP-1 Peptides Explained: GLP-1, Semaglutide, Tirzepatide, RetatrutideFrom endogenous GLP-1 to dual and triple agonists—an educational map of incretin peptide science and metabolic drug design.
- PharmacologyGLP-1 and Incretin Peptide Half-Lives Compared: From 2 Minutes to 8 DaysA sourced table of the plasma half-lives of native GLP-1, exenatide, liraglutide, dulaglutide, semaglutide, tirzepatide, retatrutide, cagrilintide and the newer co-agonists — and the three engineering strategies (DPP-4 resistance, albumin binding, Fc fusion) that stretch minutes into a week.
Related peptides
References & further reading
- 1.Garvey et al. (2025). Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med
- 2.Lau 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
- 3.Frias 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
- 4.D'Ascanio et al. (2024). Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity. Cardiol Rev
- 5.Dutta et al. (2024). Efficacy and Safety of Cagrilintide Alone and in Combination with Semaglutide (Cagrisema) as Anti-Obesity Medications: A Systematic Review and Meta-Analysis. Indian J Endocrinol Metab
- 6.Enebo 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
- 7.Kruse et al. (2021). Development of Cagrilintide, a Long-Acting Amylin Analogue. J Med Chem
- 8.Carvas et al. (2025). Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3. EBioMedicine
- 9.PubChem — compound summary for Cagrilintide (CID 171397054)
- 10.Wikipedia — Cagrilintide