Cagrilintide
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Long-acting acylated amylin analog that promotes satiety and weight loss via amylin receptor agonism in the brainstem, designed for once-weekly subcutaneous dosing.
Quick Facts
| Property | Value |
|---|---|
| Also Known As | NN9838, AM833 |
| Category | Metabolic / Weight Loss |
| Sequence | Modified amylin analog (acylated for albumin binding) |
| Molecular Weight | ~4026 Da |
| Molecular Formula | Modified peptide with C18 fatty diacid acylation |
| PubChem CID | 163314814 |
| Administration | SubQ (once weekly) |
| Typical Dose Range | 0.3-4.5 mg weekly (Phase 2); 2.4 mg weekly (Phase 3 CagriSema) |
| Half-Life | ~7 days (168 hours) |
| Storage | 2-8C; protect from light; do not freeze |
| FDA Status | Not approved as monotherapy; CagriSema combination in Phase 3 |
| WADA Status | Not specifically listed (metabolic modifier) |
Mechanism of Action
Cagrilintide is a long-acting analog of human amylin (islet amyloid polypeptide, IAPP), a 37-amino acid hormone co-secreted with insulin from pancreatic beta cells in response to meals. Native amylin has a very short half-life (~15 minutes) and tends to aggregate into amyloid fibrils. Cagrilintide overcomes both limitations through strategic amino acid substitutions (preventing fibrillation) and C18 fatty diacid acylation (enabling non-covalent albumin binding for sustained release).
Cagrilintide activates amylin receptors (AMY1, AMY2, AMY3) — heterodimers of the calcitonin receptor (CTR) with receptor activity-modifying proteins (RAMPs). These receptors are concentrated in the area postrema and nucleus of the solitary tract in the brainstem, key appetite-regulating regions. Activation produces satiety by slowing gastric emptying, reducing meal size, and modulating reward-based eating behavior. Recent research has confirmed that the weight-lowering effects are mediated through brain amylin receptors 1 and 3 specifically.
The mechanism is distinct from and complementary to GLP-1 receptor agonism, which is why the cagrilintide + semaglutide combination (CagriSema) produces additive weight loss effects (PMID: 33894838). In the Phase 1b study, the combination produced up to 17.1% weight loss over 20 weeks.
Key Research Areas
- Obesity treatment (monotherapy) — Phase 2 trial showed 6-11% weight loss over 26 weeks (PMID: 34798060)
- CagriSema combination — Cagrilintide + semaglutide for enhanced weight loss; Phase 3 program ongoing
- Type 2 diabetes — CagriSema improves glycemic control beyond GLP-1 agonist alone (PMID: 37364590)
- Amylin receptor pharmacology — Long-acting amylin analog design and receptor selectivity
- Satiety mechanisms — Brainstem-mediated appetite regulation distinct from GLP-1 pathway
Evidence Level Summary
| Evidence Type | Count | Notes |
|---|---|---|
| Human RCTs | 3 | Phase 2 monotherapy, Phase 1b combination, Phase 2 T2D |
| Human observational | 0 | N/A |
| Animal in vivo | 2+ | Receptor mechanism studies |
| In vitro | 1+ | Receptor binding characterization |
| Systematic reviews | 0 | Too early in development |
Clinical Applications
- Weight Management — Primary indication; significant weight loss as monotherapy or combination
- Fat Loss — Body composition improvement through sustained appetite suppression
- Type 2 Diabetes — Glycemic improvement when combined with semaglutide (CagriSema)
- Metabolic Syndrome — Secondary metabolic parameter improvements with weight loss
Protocols Using This Peptide
Ageless Peps Products
- AP-Cagrilintide-Vial — Cagrilintide Vial
Dosing Reference
Research Dosing Ranges (from literature)
| Route | Dose Range | Frequency | Duration | Source |
|---|---|---|---|---|
| SubQ | 0.3-4.5 mg | Once weekly | 26 weeks | PMID 34798060 (Phase 2) |
| SubQ | 2.4 mg | Once weekly | 20 weeks | PMID 33894838 (with semaglutide) |
| SubQ | 2.4 mg | Once weekly | 68 weeks | Phase 3 CagriSema (REDEFINE trials) |
Cycling
No cycling data available. Clinical trials used continuous dosing for 26-68 weeks. The long half-life (~7 days) supports weekly dosing with stable plasma concentrations. Discontinuation should be gradual given potential for weight regain.
Contraindications & Safety
- Contraindications: Personal or family history of medullary thyroid carcinoma (theoretical, extrapolated from GLP-1 class), multiple endocrine neoplasia type 2 (MEN2), pancreatitis history
- Common side effects: Nausea (most common), vomiting, diarrhea, constipation, injection site reactions, headache
- Drug interactions: May slow gastric emptying; caution with oral medications requiring rapid absorption; additive GI effects with GLP-1 agonists
- Pregnancy/nursing: Contraindicated (no reproductive safety data)
- Special populations: Not studied in severe renal or hepatic impairment; no pediatric data
Synergistic Combinations
- Semaglutide + Cagrilintide — The CagriSema combination; amylin + GLP-1 dual pathway produces greater weight loss than either alone
- AOD-9604 + Cagrilintide — Central appetite suppression + peripheral lipolysis
- MOTS-C + Cagrilintide — Metabolic energy balance + satiety signaling
Related Research
| PMID | Title | Year | Study Type |
|---|---|---|---|
| PMID-34798060 – Cagrilintide Phase 2 Weight Management Trial | Once-weekly cagrilintide for weight management | 2021 | RCT |
| PMID-33894838 – Cagrilintide Semaglutide Phase 1b PK and Safety | Cagrilintide with semaglutide Phase 1b | 2021 | RCT |
| PMID-34288673 – Development of Cagrilintide Long-Acting Amylin Analogue | Development of cagrilintide | 2021 | Narrative Review |
References
- PMID 34798060 — Lau et al., Lancet 2021 (Phase 2 dose-finding)
- PMID 33894838 — Enebo et al., Lancet 2021 (Phase 1b combination)
- PMID 34288673 — Lau et al., JCEM 2021 (development review)
Related
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