Overview
Cagrilintide is a long-acting amylin analogue developed by Novo Nordisk, engineered using fatty acid acylation technology (the same approach used in semaglutide) to extend its half-life to approximately once-weekly dosing. Amylin is a hormone co-secreted with insulin by pancreatic beta cells that contributes to satiety, slows gastric emptying, and suppresses glucagon secretion. Cagrilintide research is directed at reproducing and extending these effects for use in obesity and, in combination, type 2 diabetes research.
The compound has been most prominently studied as part of "CagriSema," a fixed-dose combination of cagrilintide and semaglutide (a GLP-1 receptor agonist), on the basis that amylin and GLP-1 pathways act on complementary, partially non-overlapping appetite and satiety circuits, offering a rationale for combined-pathway research beyond what either agent achieves alone. This guide is for educational and research purposes only. Not medical advice.
Clinical & Research Status
| Evidence Type |
Status |
| Human RCT |
✔ |
| Observational |
✗ |
| Animal Studies |
✔ |
| In Vitro |
✔ |
| Regulatory Approval |
✗ (not yet approved; under regulatory review as part of CagriSema as of the compound's most recent trial data) |
Mechanism of Action
Cagrilintide acts as an agonist at amylin receptors (formed from calcitonin receptor core proteins complexed with receptor activity-modifying proteins), as well as showing some activity at calcitonin receptors. Amylin receptor activation in the area postrema and hypothalamus contributes to reduced food intake through mechanisms distinct from, but complementary to, GLP-1 receptor signalling — including slowed gastric emptying and reduced meal size via central satiety pathways.
The fatty acid acylation used in cagrilintide's design (analogous to the modification used in semaglutide) allows the peptide to bind reversibly to albumin in the bloodstream, protecting it from rapid renal clearance and enzymatic degradation, and extending its half-life to support once-weekly subcutaneous dosing. In the CagriSema combination, cagrilintide's amylin-pathway effects on satiety and gastric emptying are researched as additive to semaglutide's GLP-1-mediated effects on appetite and insulin secretion.
Research Areas & Reported Effects
Monotherapy Weight Management Trials
Phase II trials of cagrilintide as a standalone agent reported dose-dependent weight loss in people with obesity, with higher doses (2.4 mg weekly) associated with meaningfully greater weight reduction than placebo over 26 weeks in published trial data.
CagriSema Combination (Cagrilintide + Semaglutide)
The REDEFINE Phase 3 trial programme evaluated CagriSema in people with obesity and overweight, including participants with and without type 2 diabetes. Published REDEFINE 1 results (2024) reported average weight loss of approximately 20.4% over 68 weeks in participants without diabetes on CagriSema, compared with a smaller reduction on semaglutide alone and placebo, though the results in participants with type 2 diabetes (REDEFINE 2) showed a smaller magnitude of weight loss than had been anticipated, prompting continued research interest in optimising the combination and dosing strategy.
Glycaemic and Metabolic Parameters
Trials assessing CagriSema in populations with type 2 diabetes have reported reductions in HbA1c alongside weight loss, consistent with the complementary glucagon-suppressing and satiety-enhancing mechanisms of amylin and GLP-1 receptor pathways studied together.
Research Data Summary
| Study / Model |
Reported Effect |
| Phase Ib/II Monotherapy Trial (Lau DCW et al., Lancet 2021) |
Reported dose-dependent weight loss with cagrilintide monotherapy versus placebo over 26 weeks, with favourable tolerability at studied doses. |
| REDEFINE 1 Phase 3 (2024, NEJM/company disclosure) |
CagriSema reported approximately 20.4% mean weight loss at 68 weeks in adults with obesity/overweight without diabetes, versus semaglutide alone and placebo comparator arms. |
| REDEFINE 2 Phase 3 (2024, type 2 diabetes population) |
Reported weight loss and HbA1c reduction in participants with type 2 diabetes, though weight-loss magnitude was reported as below internal expectations, prompting continued analysis. |
| Preclinical Rodent Amylin Receptor Studies |
Confirmed amylin/calcitonin receptor agonism and reduced food intake in rodent obesity models, supporting the translational rationale for human trials. |
Stack Combinations Studied
- Cagrilintide + Semaglutide (CagriSema) → Research rationale: The primary studied combination — pairing an amylin receptor agonist with a GLP-1 receptor agonist to target complementary appetite and satiety pathways, studied extensively in the Phase 3 REDEFINE programme.
- Cagrilintide monotherapy → Research rationale: Studied independently in earlier Phase Ib/II trials to characterise the isolated effect of amylin receptor agonism prior to combination trials.
⚠️ Stack combinations listed for research reference only. Not safety or efficacy guidance.
Research Protocol Reference
experimental research protocols only — not dosing recommendations.
| Protocol |
Dose (experimental model only) |
Duration (experimental model only) |
Frequency (experimental model only) |
Research Context |
| Low-Dose Titration Protocol (as trialled) |
0.25-0.5 mg |
4-week titration steps |
Once weekly, subcutaneous |
Dose escalation to minimise gastrointestinal tolerability issues, matching REDEFINE trial design. |
| Standard Trial Protocol (as trialled) |
Up to 2.4 mg (monotherapy) or CagriSema fixed-dose equivalent |
68 weeks (REDEFINE 1) |
Once weekly, subcutaneous |
Matches Phase 3 REDEFINE trial dosing for weight management research. |
Observed Side Effects in Research
- Gastrointestinal effects (nausea, vomiting, diarrhoea, constipation) — most common, consistent with amylin/GLP-1 pathway agents
- Injection site reactions
- Reduced appetite (expected pharmacological effect)
- Discontinuation due to gastrointestinal adverse events reported in a subset of trial participants, similar in pattern to other incretin/amylin-pathway agents
Reported safety profile across REDEFINE trials was broadly consistent with the known tolerability profile of GLP-1 and amylin receptor agonists as a drug class; no unexpected safety signals specific to cagrilintide were highlighted in published Phase 3 data as of the most recent trial readouts.
Compound Data
- CAS Number
- 1849590-01-9
- Molecular Formula
- C217H358N48O66 (approximate, long-acting acylated amylin analogue)
- Molecular Weight
- Approximately 4691 g/mol
- Half-Life
- Approximately 7 days (supports once-weekly subcutaneous dosing), due to fatty-acid albumin-binding modification
- Synonyms
- NNC0174-0833, Cagrilintide (INN), component of CagriSema (with semaglutide)
- Research Classification
- Long-Acting Amylin Analogue, Amylin/Calcitonin Receptor Agonist
Scientific References
- [Lau DCW 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. — The Lancet — [Human RCT]
- [Novo Nordisk, REDEFINE 1 Trial Results 2024] — CagriSema in adults with overweight or obesity: Phase 3 results. — New England Journal of Medicine / company disclosure — [Human RCT]
- [Novo Nordisk, REDEFINE 2 Trial Results 2024] — CagriSema in adults with type 2 diabetes and overweight or obesity: Phase 3 results. — Company clinical trial disclosure — [Human RCT]
- [Enebo LB et al. 2021] — Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management. — The Lancet — [Human RCT, Phase Ib]
Research base note: Cagrilintide has a well-documented Phase 2 and Phase 3 clinical trial record, primarily as part of the CagriSema combination, published in high-impact peer-reviewed journals and company disclosures. As of the most recent published data, cagrilintide/CagriSema had not yet completed full regulatory approval; readers should check current regulatory status independently before treating any approval-related claim as final.
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