Cagrilintide

For laboratory research use only. Not for human consumption or veterinary use.

Structural Overview

Cagrilintide (development code AM833) is a 37-amino-acid synthetic analog of human amylin (islet amyloid polypeptide, IAPP) engineered for selective activation of the AMY1R complex — the heterodimer formed by the calcitonin receptor (CTR) and receptor-activity-modifying protein 1 (RAMP1). The C-terminal fatty-acid acylation enables albumin binding and extends circulating half-life to ~7 days in published research-model pharmacokinetics. CAS 1415456-99-3; molecular weight 4409.01 g/mol.

Receptor Pharmacology

Native amylin is co-secreted from pancreatic β-cells with insulin and acts at AMY1R in the area postrema, nucleus tractus solitarius, and hypothalamic regions controlling satiety and gastric emptying. Cagrilintide preserves this receptor selectivity through engineered substitutions characterized by Kruse et al. (J Med Chem 2021, DOI 10.1021/acs.jmedchem.1c00565). The amylin pathway is mechanistically non-overlapping with the GLP-1 / GIP / glucagon incretin axis, which underlies the additive research-model effects observed when cagrilintide is studied in combination with incretin agonists.

Published Phase 2 and Phase 3 Research Outcomes

Phase 2 monotherapy dose-finding work (Lau DCW et al., The Lancet 2021, PMID 34798060) established once-weekly cagrilintide pharmacology. Phase 2 combination with semaglutide in T2DM (Frias JP et al., The Lancet 2023, PMID 37364590) demonstrated tolerability of the co-administration regimen. The Phase 3 REDEFINE-1 trial (Garvey WT et al., NEJM 2025, PMID 40544433) reported approximately 22.7% mean body-weight reduction with the co-administered cagrilintide + semaglutide combination (CagriSema) at 68 weeks. The regional Phase 3 REDEFINE-5 (Yamauchi T et al., Lancet Diabetes & Endocrinology 2026, PMID 42009015) extended these findings to Japanese and Taiwanese research populations. No human dosing, administration route, reconstitution, or therapeutic protocol is provided — these are reported research outcomes from published primary literature only.

Regulatory Status

Cagrilintide is not FDA-approved for any human indication as a standalone product. Novo Nordisk’s CagriSema combination filing is the active regulatory path, with PDUFA action anticipated in late 2026. Standalone cagrilintide has no approved marketing context. There is no 503A/503B compounding pathway for cagrilintide. For research use only.

Counter-Evidence and Safety Context (Disclosed Honestly)

Cagrilintide monotherapy efficacy is modest relative to the combination: Phase 2 monotherapy reached approximately 10–11% body-weight reduction; the headline ~22.7% figure is specifically for the CagriSema combination with semaglutide. Researchers comparing cagrilintide to GLP-1 monotherapy alone should expect substantially lower standalone effect sizes. Published Phase 2/3 trials (Frias PMID 37364590; Garvey PMID 40544433) document nausea, vomiting, and diarrhea as dose-related adverse events consistent with the broader incretin-class profile. REDEFINE-2 (T2DM) and REDEFINE-3 (head-to-head vs tirzepatide) are pending peer-reviewed publication at time of this writing.

Supply Chain Integrity

Cagrilintide is one of three peptides — with retatrutide and tirzepatide — currently subject to elevated grey-market quality risk per industry reports. Independent third-party testing from late 2024 through early 2026 documented widespread quality failures across a significant share of sampled vendors selling these three peptides. Each Artemis Labs vial ships with a lot-specific Certificate of Analysis from a named third-party laboratory, mass-spectrometric identity confirmation (MW 4409.01 g/mol target), HPLC purity chromatogram (≥99% target), residual-solvent assay, and chain-of-custody documentation from manufacture through shipping. See the reading a Certificate of Analysis guide for the verification framework.

For laboratory research use only. No human dosing, administration, therapeutic, diagnostic, or preventative claim is made. These statements have not been evaluated by the FDA.

Science & Research

Structural Pharmacology

Cagrilintide (AM833) is a 37-amino-acid synthetic analog of human amylin (islet amyloid polypeptide, IAPP). It carries C-terminal fatty-acid acylation that enables albumin binding and extends circulating half-life to approximately 7 days in published research-model pharmacokinetics. CAS 1415456-99-3; molecular weight 4409.01 g/mol. Structural and selectivity engineering is characterized in Kruse et al. (J Med Chem 2021, DOI 10.1021/acs.jmedchem.1c00565).

AMY1R Receptor Selectivity

Cagrilintide is engineered for preferential activation of the AMY1R complex — the heterodimer of the calcitonin receptor (CTR) and receptor-activity-modifying protein 1 (RAMP1). Native amylin is co-secreted from pancreatic β-cells with insulin and acts at AMY1R in the area postrema, nucleus tractus solitarius, and hypothalamic regions controlling satiety and gastric emptying. The CTR + RAMP1 selectivity engineering is intended to reduce calcitonin-receptor off-target signaling that would otherwise occur with non-selective amylin/calcitonin pharmacology. Reviewed in Khachaturov M et al. (Diabetes, Obesity & Metabolism 2026, PMID 42098899) within the broader amylin-analog and combination landscape.

Mechanistic Basis for Combination with Incretin Agonists

The published rationale for studying cagrilintide in combination with GLP-1 (semaglutide) is mechanistic non-overlap: amylin (AMY1R) and GLP-1 (GLP-1R) act through distinct G-protein-coupled receptor pathways and engage distinct neural circuits. AMY1R signaling proceeds primarily through Gαs / cAMP pathways in CTR-expressing satiety neurons; GLP-1R signaling also engages Gαs / cAMP but through anatomically and functionally distinct receptor populations. The published Phase 3 outcome (Garvey et al. 2025, PMID 40544433) reports the magnitude of additive effect across this co-administration in research populations.

Published Phase 2 and Phase 3 Research

• Phase 2 monotherapy — Lau DCW et al. (2021). “Once-weekly cagrilintide for weight management in people with overweight and obesity: a phase 2 trial.” The Lancet. PMID 34798060. Established dose-finding pharmacology.
• Phase 2 CagriSema in T2DM — Frias 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.” The Lancet. PMID 37364590. Combination tolerability in T2DM research populations.
• Phase 3 REDEFINE-1 — Garvey WT et al. (2025). “Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity.” NEJM. PMID 40544433. Approximately 22.7% mean body-weight reduction with CagriSema at 68 weeks.
• Phase 3 REDEFINE-5 (regional) — Yamauchi T et al. (2026). “Co-administered cagrilintide and semaglutide versus semaglutide alone.” Lancet Diabetes & Endocrinology. PMID 42009015. Regional Phase 3 evidence extending REDEFINE-1 to Japanese and Taiwanese populations.

Regulatory Status

Cagrilintide is not FDA-approved for any human indication as a standalone product. The CagriSema combination filing (Novo Nordisk) is the active regulatory path; PDUFA action anticipated late 2026. No 503A/503B compounding pathway applies. For research use only.

Counter-Evidence and Limitations (Disclosed Honestly)

• Monotherapy effect size is modest relative to combination (~10–11% Phase 2 monotherapy vs ~22.7% CagriSema Phase 3). Do not extrapolate combination figures to monotherapy contexts.
• GI adverse events (nausea, vomiting, diarrhea) consistent with broader incretin-class profile in the combination context (Frias 2023 PMID 37364590; Garvey 2025 PMID 40544433).
• REDEFINE-2 (T2DM) and REDEFINE-3 (head-to-head vs tirzepatide) are pending peer-reviewed publication; head-to-head class-comparator outcome data not yet available.
• Long-term safety data beyond Phase 3 trial durations is not yet published.

Reference List (verified PubMed citations)

1. Lau DCW et al. (2021). Once-weekly cagrilintide for weight management. The Lancet. PMID 34798060
2. Frias JP et al. (2023). Co-administered cagrilintide + semaglutide in T2DM (Phase 2). The Lancet. PMID 37364590
3. Garvey WT et al. (2025). REDEFINE-1 Phase 3 CagriSema in obesity. NEJM. PMID 40544433
4. Yamauchi T et al. (2026). REDEFINE-5 regional Phase 3. Lancet Diabetes Endocrinol. PMID 42009015
5. Khachaturov M et al. (2026). Multi-agonists, amylin analogues, and combination strategies. Diabetes Obes Metab. PMID 42098899
6. Chan ZH et al. (2026). Incretin-based dual and triple agonists meta-analysis. Cardiology in Review. PMID 41711462

For laboratory research use only. No human dosing, administration, therapeutic, diagnostic, or preventative claim is made. These statements have not been evaluated by the FDA.

Stacks

Stacking commentary below is restricted to in-vitro and pre-clinical research-design rationale. No dosing, frequency, route, or human protocol is provided.

Research-Design Rationale: Cagrilintide + Semaglutide (CagriSema mechanistic basis)

The published Phase 2/3 rationale for studying cagrilintide alongside semaglutide is mechanistic non-overlap. Amylin and GLP-1 are anatomically and pharmacologically distinct satiety pathways: amylin acts through AMY1R (CTR + RAMP1) in the area postrema, nucleus tractus solitarius, and hypothalamus; GLP-1 acts through GLP-1R in overlapping but distinct neural populations. The Phase 3 REDEFINE-1 trial (Garvey WT et al., NEJM 2025, PMID 40544433) is the published evidence base for the additive research-model effect.

Comparator Compounds in the Artemis Catalog

• Tirzepatide — Dual GIP + GLP-1 incretin agonist; parallel-pathway comparator in receptor-binding research.
• Retatrutide — Triple GIP + GLP-1 + glucagon agonist; parallel-comparator framing for amylin satiety pathway versus incretin-driven thermogenic agonism.
• AOD-9604 — HGH-fragment-derived lipolytic peptide; adipose-tissue research models contrasting amylin-mediated central satiety against non-GHR adipocyte signaling.

Comparator Summary Table

For deeper class context see the Complete Guide to Weight Loss Research Peptides (2026) and the Tirzepatide vs. Retatrutide Comparison.

For laboratory research use only.