Cagriniltide
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Research Use Only
These products are for laboratory research only and not intended for medical use. They are not FDA-approved to diagnose, treat, cure, or prevent any disease. By purchasing, you certify they will be used solely for research and not for human or animal consumption.
Research Summary
19 PubMed CitationsResearch Overview Cagriniltide (AM833/NN1213) is a long-acting acylated analogue of human amylin — a 37-amino acid pancreatic hormone co-secreted with insulin that regulates satiety and glucose homeostasis. Native human amylin is unstable, prone to amyloid fibril formation, and has a very short half-life. The first-generation analogue, pramlintide, requires multiple daily injections.[2] Cagriniltide overcomes these limitations through C20 fatty diacid acylation (via γ-glutamic acid spacer at Lysine 1), which binds serum albumin, extending the half-life to 159–195 hours and enabling once-weekly dosing. Proline substitutions (Pro21, Pro27) and specific amino acid changes (N14E, V17R) prevent fibril formation and stabilize the peptide's alpha-helix.[3] The primary therapeutic strategy involves co-administration with semaglutide (branded as CagriSema). While GLP-1 agonists target incretin pathways, cagriniltide targets distinct amylin and calcitonin receptors in the hindbrain, activating non-overlapping satiety pathways for synergistic weight loss of up to 22.7% — significantly exceeding either monotherapy.[5][11]
Cagriniltide — Research Data at a Glance
| Property | Value |
|---|---|
| PubMed Citations Referenced | 19 |
| Contributing Researchers | 3 |
| Storage Conditions | Lyophilized: -80°C (2 years) or -20°C (1 year); Reconstituted: -80°C (6 months) or -20°C (1 month); aliquot to prevent degradation. |
| Purity Standard | ≥99% (HPLC verified, 3rd-party COA) |
| Research Use Only | Not for human consumption. RUO only. |
Overview
Research Overview
Cagriniltide (AM833/NN1213) is a long-acting acylated analogue of human amylin — a 37-amino acid pancreatic hormone co-secreted with insulin that regulates satiety and glucose homeostasis. Native human amylin is unstable, prone to amyloid fibril formation, and has a very short half-life. The first-generation analogue, pramlintide, requires multiple daily injections.[2]
Cagriniltide overcomes these limitations through C20 fatty diacid acylation (via γ-glutamic acid spacer at Lysine 1), which binds serum albumin, extending the half-life to 159–195 hours and enabling once-weekly dosing. Proline substitutions (Pro21, Pro27) and specific amino acid changes (N14E, V17R) prevent fibril formation and stabilize the peptide's alpha-helix.[3]
The primary therapeutic strategy involves co-administration with semaglutide (branded as CagriSema). While GLP-1 agonists target incretin pathways, cagriniltide targets distinct amylin and calcitonin receptors in the hindbrain, activating non-overlapping satiety pathways for synergistic weight loss of up to 22.7% — significantly exceeding either monotherapy.[5][11]
Mechanism of Action
Mechanism of Action
Cagriniltide functions as a non-selective dual agonist of both calcitonin receptors (CTR) and amylin receptors (AMY1R, AMY2R, AMY3R) — heterodimers of CTR with RAMPs 1, 2, or 3.[3][12]
Receptor Targets & Binding
| Target | Interaction | Evidence |
|---|---|---|
| Calcitonin Receptor (CTR) | Non-selective agonist; class B1 GPCR; EC50 62 pM | Kruse et al. (2021); Cao et al. (2025) cryo-EM[3][9] |
| AMY1R (CTR+RAMP1) | Potent agonist; "bypass" conformation binding | RAMP1/3 KO abolishes weight-loss effects[8] |
| AMY3R (CTR+RAMP3) | Potent agonist; EC50 49 pM (hAMY3R) | Carvas et al. (2025): essential for efficacy[8][13] |
| CGRPR / AM1R / AM2R | No or very low activity — selective for amylin/calcitonin axis | Fletcher et al. (2021)[12] |
Downstream Signaling
| Pathway | Effect | Consequence |
|---|---|---|
| Gs / Adenylyl Cyclase / cAMP | Gs-protein activation → adenylyl cyclase → intracellular cAMP accumulation | Primary signaling cascade for satiety[9] |
| Neuronal cFos (AP/NTS/LPBN) | Induces cFos expression in area postrema, nucleus of solitary tract, lateral parabrachial nucleus | Satiety signaling; 57% fewer AP neurons in RAMP1/3 KO[8] |
| Gastric Emptying | Delays gastric emptying → prolonged postprandial fullness | Reduced caloric intake; may affect oral drug absorption |
| Glucagon Suppression | Suppresses postprandial glucagon from pancreatic α-cells | Improved glycemic control without hypoglycemia risk[6] |
Unique Binding Characteristics
| Property | Cagriniltide | Salmon Calcitonin |
|---|---|---|
| Receptor Conformation | "Bypass" (stabilized by ionic lock N14E–V17R) | "CT-like" conformation |
| Residence Time | 3–6 minutes (rapid dissociation) | 45–60 minutes (slow dissociation) |
| Desensitization | Prevents receptor downregulation → sustained weight loss | Causes receptor downregulation → weight regain |
RAMP Dependence: Carvas et al. (2025) demonstrated that the weight-lowering and anorectic effects of cagriniltide are strictly dependent on AMY1R and AMY3R — knockout of RAMP1 and RAMP3 completely abolished drug efficacy, with 57% fewer neurons activated in the area postrema.[8]
Research Applications
Research Applications
Cagriniltide is currently evaluated in late-stage clinical trials across 4+ research domains:
- Obesity & Weight Management — CagriSema (cagriniltide + semaglutide) achieved 20.4–22.7% weight loss in Phase 3 REDEFINE 1 trial (n=3,417), significantly outperforming semaglutide monotherapy (15–16%) and cagriniltide monotherapy (11.8%). Targets the "weight loss plateau" seen with single-agent GLP-1 therapy.[5]
- Type 2 Diabetes — REIMAGINE 2 trial (n=2,728) demonstrated HbA1c reduction of 1.91% with CagriSema vs 1.76% with semaglutide alone (superiority); 73.5% achieved HbA1c <6.5%. Phase 2 data showed HbA1c reduction of -2.2%.[6][4]
- Cardiovascular Risk Reduction — REDEFINE 1 post-hoc analysis showed systolic blood pressure decreased -10.9 mmHg with CagriSema vs -2.1 mmHg placebo. Significant reduction in hsCRP inflammatory markers. Dedicated REDEFINE 3 MACE outcomes trial is ongoing.[7]
- Combination Therapy for Resistant Phenotypes — Research explores utility for patients failing GLP-1 monotherapy or requiring bariatric-surgery-level weight management. Theoretical combinations with triple agonists (e.g., retatrutide) under investigation.[14]
- Receptor Pharmacology — Cryo-EM structural biology of dual AMYR/CTR agonism; RAMP-dependent signaling; "bypass" vs "CT-like" receptor conformations; rapid-dissociation kinetics preventing desensitization.[9][10]
Biochemical Characteristics
| Property | Value |
|---|---|
| Molecular Formula | C₁₉₄H₃₁₂N₅₄O₅₉S₂ |
| Molecular Weight | 4409.01 Da |
| CAS Number | 1415456-99-3 |
| PubChem CID | 171397054 |
| Sequence (1-Letter) | K(Eicosanedioic acid-γ-Glu)-CNTATCATQRLAEFLRHSSNNFGPILPPTNVGSNTP-NH₂ |
| Sequence (3-Letter) | {Eicosanedioic acid-γ-Glu}-Lys-Cys-Asn-Thr-Ala-Thr-Cys-Ala-Thr-Gln-Arg-Leu-Ala-Glu-Phe-Leu-Arg-His-Ser-Ser-Asn-Asn-Phe-Gly-Pro-Ile-Leu-Pro-Pro-Thr-Asn-Val-Gly-Ser-Asn-Thr-Pro-NH₂ |
| Structure | 37-amino acid lipidated amylin analogue; C20 fatty diacid via γ-Glu spacer at Lys1; Cys2–Cys7 disulfide bridge; Pro21/Pro27 anti-fibrillation substitutions; N14E/V17R ionic lock |
| Origin | Engineered from human amylin scaffold by Novo Nordisk A/S |
| Classification | Long-Acting Amylin Analogue / DACRA / Research Peptide |
| Half-Life | ~159–195 hours (human); ~24h (rat), ~50h (rabbit), ~76h (dog), ~115h (minipig) |
| Bioavailability | ~40% subcutaneous (rat) |
Identifiers
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| InChI Key | |
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Preclinical Research Summary
Preclinical Research Summary
Key Preclinical Studies
| Study | Model | Key Findings | Ref |
|---|---|---|---|
| Carvas et al. (2025) | 129S2/SvEv mice — WT vs RAMP1/3 KO; 3–300 nmol/kg SC | 30 nmol/kg: 24h food intake ↓51%; WT lost -3.4g (-6.6%), KO had no effect; 57% fewer AP neurons activated in KO | [8] |
| Kruse et al. (2021) | Male SD rats — 0.1–30 nmol/kg SC; PK: 10 nmol/kg IV/SC | Food intake reduced for several days at 1–10 nmol/kg; T½ 20h (IV), 27h (SC) | [3] |
| Dahl et al. (2024) | Rats — 30 nmol/kg single SC injection | Food intake reduced 85% at 0–24h and 84% at 24–48h; EC50: hAMY3R 49 pM, hCTR 62 pM | [13] |
Clinical / Human Studies
| Trial | Design | Key Results | Outcome |
|---|---|---|---|
| REDEFINE 1 NCT05567796 | Phase 3; n=3,417; 68-week RCT; CagriSema 2.4/2.4mg vs sema vs cagri vs placebo | Weight loss: 22.7% (CagriSema) vs 15–16% (sema) vs 11.8% (cagri); SBP -10.9 mmHg; GI AEs 79.6% | SUCCESS[5] |
| REDEFINE 2 NCT05394519 | Phase 3; n=1,206; 68-week RCT in T2D; CagriSema vs placebo | Weight loss: 13.7% vs 3.4%; 73.5% achieved HbA1c <6.5% vs 15.9% | SUCCESS[6] |
| REIMAGINE 2 NCT06065540 | Phase 3; n=2,728; 68-week active-controlled; CagriSema vs sema 2.4mg | HbA1c: -1.91% vs -1.76% (superiority); weight: 14.2% vs 10.2% | SUCCESS |
| Phase 2 T2D | n=92; 32-week; CagriSema vs sema vs cagri | HbA1c: -2.2% (CagriSema) vs -1.8% vs -0.9%; weight: -15.6% vs -5.1% vs -8.1% | SUCCESS[4] |
| Phase 2 Obesity | n=706; 26-week dose-finding; cagri (0.3–4.5mg) vs liraglutide vs placebo | 4.5mg: 10.8% loss; 2.4mg: 8.9%; liraglutide 3.0mg: 9.0% | SUCCESS[2] |
| Phase 1b | n=95; 20-week; cagri 2.4mg + sema 2.4mg | Weight loss: 17.1% vs 9.8% (sema alone) | SUCCESS[1] |
The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body. These products are not medicines or drugs and have not been approved by the FDA to prevent, treat or cure any medical condition, ailment or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law.
For Laboratory Research Only. Not for human use, medical use, diagnostic use, or veterinary use.
ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY.
Authors & Attribution
✍️ Article Author
Thomas Kruse
Thomas Kruse is a lead scientist at Novo Nordisk A/S in Måløv, Denmark. He played a central role in the chemical development and structural engineering of cagriniltide, leading the structure-activity relationship (SAR) efforts to create a long-acting, stable amylin analog that activates both amylin receptors and the calcitonin receptor while overcoming the instability and fibrillation issues of native human amylin. His key publications include "Development of Cagrilintide, a Long-Acting Amylin Analogue" (2021, Journal of Medicinal Chemistry) and "NN1213 – A Potent, Long-Acting, and Selective Analog of Human Amylin" (2024, Journal of Medicinal Chemistry). Thomas Kruse is being referenced as one of the leading scientists involved in cagriniltide research. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor.
View Full Researcher Profile →🎓 Scientific Journal Author
W. Timothy Garvey, MD
W. Timothy Garvey, MD is a professor in the Department of Nutrition Sciences at the University of Alabama at Birmingham. He served as principal investigator for the pivotal Phase 3 REDEFINE program evaluating cagriniltide combined with semaglutide (CagriSema) for weight loss. His landmark trial demonstrated 22.7% weight loss with CagriSema in 3,417 adults with overweight or obesity, along with significant cardiovascular benefits including 10.9 mmHg systolic blood pressure reduction. His key publications include "Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity" (2025, New England Journal of Medicine) and "CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1" (2026, Hypertension). W. Timothy Garvey is being referenced as one of the leading scientists involved in cagriniltide research. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor.
View Full Researcher Profile →W. Timothy Garvey, MD is being referenced as one of the leading scientists involved in the research and development of Cagriniltide. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor. The purpose of citing the doctor is to acknowledge, recognize, and credit the exhaustive research and development efforts conducted by the scientists studying this peptide.
🔬 Contributing Researcher
David C.W. Lau, MD, PhD
David C.W. Lau, MD, PhD is based at the Julia McFarlane Diabetes Research Centre and Libin Cardiovascular Institute of Alberta, University of Calgary Cumming School of Medicine. He led the Phase 2 dose-finding study and Phase 1b safety/tolerability trials that established the dose-dependent weight loss effects of cagriniltide monotherapy and its safety profile when co-administered with semaglutide. His key publications include "Once-weekly cagrilintide for weight management in people with overweight and obesity" (2021, The Lancet) and "Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of cagrilintide with semaglutide" (2021, The Lancet). David C.W. Lau is being referenced as one of the leading scientists involved in cagriniltide research. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor.
View Full Researcher Profile →David C.W. Lau, MD, PhD is being referenced as one of the leading scientists involved in the research and development of Cagriniltide. In no way is this doctor/scientist endorsing or advocating the purchase, sale, or use of this product for any reason. There is no affiliation or relationship, implied or otherwise, between Pure US Peptide and this doctor. The purpose of citing the doctor is to acknowledge, recognize, and credit the exhaustive research and development efforts conducted by the scientists studying this peptide.
Referenced Citations
Enebo LB, et al. 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, 397(10286), 1736-1748, 2021.
PubMedLau DCW, et al. 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, 398(10317), 2160-2172, 2021.
PubMedKruse T, et al. Development of Cagrilintide, a Long-Acting Amylin Analogue. Journal of Medicinal Chemistry, 64(15), 11183-11194, 2021.
PubMedFrias JP, et al. 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, 402(10403), 720-730, 2023.
PubMedGarvey WT, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine, 393(7), 635-647, 2025.
PubMedDavies MJ, et al. Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. New England Journal of Medicine, 393(7), 648-659, 2025.
PubMedVerma S, et al. CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1. Hypertension, 83(2), e26055, 2026.
PubMedCarvas AO, et al. Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3. EBioMedicine, 118, 105836, 2025.
PubMedCao J, et al. Structural and dynamic features of cagrilintide binding to calcitonin and amylin receptors. Nature Communications, 16, 3389, 2025.
PubMedGu YM, et al. Structural and mechanistic insights into dual activation of cagrilintide in amylin and calcitonin receptors. Acta Pharmacologica Sinica, 47(1), 162-172, 2026.
PubMedWang Y, Feng Z, Yu L. The next frontier in metabolic health: Cagrilintide-Semaglutide and the evolving landscape of therapies. The Innovation Medicine, 3(3), 100150, 2025.
PubMedFletcher MM, et al. AM833 Is a Novel Agonist of Calcitonin Family G Protein-Coupled Receptors: Pharmacological Comparison with Six Selective and Nonselective Agonists. JPET, 377(3), 417-440, 2021.
PubMedDahl K, et al. NN1213 – A Potent, Long-Acting, and Selective Analog of Human Amylin. Journal of Medicinal Chemistry, 67(14), 11688–11700, 2024.
PubMedBecerril S, Frühbeck G. Cagrilintide plus semaglutide for obesity management. Lancet, 397(10286), 1687-1689, 2021.
PubMedD'Ascanio AM, et al. Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity. Cardiology in Review, 32(1), 83-90, 2024.
PubMedMikhail N, Wali S. Cagrilintide Combined with Semaglutide: A New Approach for Treatment of Obesity and Type 2 Diabetes. Clinical Trials and Clinical Research, 2(5), 2023.
PubMedHales CM. Expanding the Treat-to-Target Toolbox for Obesity and Diabetes Care. New England Journal of Medicine, 393(7), 712-714, 2025.
PubMedGadde KM, Allison DB. Long-acting amylin analogue for weight reduction. Lancet, 398(10317), 2132-2134, 2021.
PubMedDehestani B, et al. Amylin as a Future Obesity Treatment. Journal of Obesity & Metabolic Syndrome, 30(4), 320-325, 2021.
PubMedRUO Disclaimer
For Research Use Only (RUO). This product is intended solely for in-vitro research and laboratory experimentation. It is not a drug, food, cosmetic, or medical device and has not been approved by the FDA for any human or veterinary use. It must not be used for therapeutic, diagnostic, or any other non-research purpose. Pure US Peptide does not condone or encourage the use of this product for anything other than strictly defined research applications. Users assume full responsibility for compliance with all applicable regulations and guidelines.
Certificate of Analysis (COA)
Every batch is strictly tested by accredited third-party laboratories (ISO 17025) to ensure 99%+ purity.
Latest Lab Report
Storage & Handling
Summary
Lyophilized: -80°C (2 years) or -20°C (1 year); Reconstituted: -80°C (6 months) or -20°C (1 month); aliquot to prevent degradation.
Lyophilized Powder
Store at -80°C for up to 2 years or -20°C for up to 1 year. Keep sealed, away from moisture and light, preferably under inert gas (N₂).
Reconstituted Solution
Store at -80°C for up to 6 months or -20°C for up to 1 month. Aliquot stock solutions to prevent freeze-thaw cycles which degrade the peptide.
Handling
White to off-white powder. Purity: ≥95–99.97% by HPLC/UPLC. Identity: LC-MS (~4409.01 Da). Physical stability: Thioflavin T (ThT) assay confirms >40 hours fibril-free under stress conditions.
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