What Is Cagrilintide? The Long-Acting Amylin Analogue
Cagrilintide is a lipidated, long-acting amylin analogue acting on amylin and calcitonin receptors. Its design, mechanism and phase 2 data.
Cagrilintide is a long-acting analogue of amylin, the satiety hormone that pancreatic beta cells secrete together with insulin. It was engineered to solve two problems with native amylin, its strong tendency to form amyloid fibrils and its short half-life, and carries a fatty acid side chain for once-weekly exposure. It is studied alone and in combination with GLP-1 receptor agonists.
For laboratory research use only. The compounds discussed are not approved for human or veterinary use and are not drugs, foods or cosmetics. This article summarises published research and is not medical advice.
Key points
- Lipidated amylin analogue; non-selective amylin and calcitonin receptor agonist.
- C194H312N54O59S2, ~4409 g/mol (PubChem).
- Designed for stability against fibril formation and for once-weekly exposure.
- Phase 2: dose-related body-weight reductions vs placebo; the highest dose exceeded a liraglutide comparator.
- Studied with semaglutide as “CagriSema”.
Quick facts
| Property | Value |
|---|---|
| Class | Amylin analogue (dual amylin/calcitonin receptor agonist) |
| Molecular formula / weight | C194H312N54O59S2, ~4409 g/mol |
| Key modifications | Lipidation (fatty acid side chain); sequence changes to reduce fibrillation |
| Developer | Novo Nordisk |
| Status | Investigational at the time of the cited trials; check FDA/EMA for current status |
Our cagrilintide research peptide is available in 5 mg and 10 mg vials with lot-level HPLC and MS data.
Why amylin is hard to make into a drug
Amylin is a 37-residue peptide with a strong propensity to form amyloid fibrils, which makes it a difficult starting point for drug design. The first amylin analogue, pramlintide, is used as an adjunct to insulin but requires three daily injections because of its short half-life (Kruse et al., 2021). Any long-acting analogue therefore has to be both chemically stabilised against aggregation and protected from rapid clearance.
How cagrilintide was designed
Kruse and colleagues at Novo Nordisk reported structure–activity work that led to cagrilintide (compound 23 in their series): a stable, lipidated, long-acting amylin analogue selected for clinical development in obesity (Kruse et al., 2021). Lipidation provides albumin binding and extends exposure, the same strategy used for long-acting GLP-1 analogues (Müller et al., 2019). Sequence modifications reduce the fibrillation tendency of native amylin.
| Problem with native amylin | Cagrilintide solution |
|---|---|
| Amyloid fibril formation | Sequence changes that improve physical stability |
| Short half-life (pramlintide: thrice-daily dosing) | Fatty acid side chain for albumin binding |
| Receptor coverage | Non-selective agonism at amylin and calcitonin receptors |
Phase 2 trial endpoints
A dose-finding phase 2 trial randomised 706 adults without diabetes and with obesity or overweight to one of several weekly cagrilintide doses, 99 to liraglutide 3.0 mg daily and 101 to placebo, for 26 weeks (Lau et al., 2021).
| Endpoint (26 weeks) | Result |
|---|---|
| Mean body-weight change, cagrilintide (range across doses) | −6.0% to −10.8% |
| Placebo | −3.0% |
| Liraglutide comparator | −9.0% (highest cagrilintide dose −10.8%, difference 1.8%, p=0.03) |
| Most frequent adverse events | Gastrointestinal disorders and administration-site reactions |
A separate phase 2 trial in type 2 diabetes tested cagrilintide co-administered with semaglutide against each component (Frias et al., 2023). These are clinical trial results for an investigational medicine and do not apply to research material.
Cagrilintide in combination research
Amylin and GLP-1 act through different receptors and partly different brain regions, which is the rationale for studying them together. In the research catalogue, cagrilintide is often compared or paired with incretin agonists such as tirzepatide and retatrutide; see cagrilintide vs retatrutide and cagrilintide and tirzepatide.
Handling in the lab
- Store lyophilized powder at −20 °C, sealed and dark.
- As a lipidated, amylin-derived peptide, cagrilintide may be prone to self-association. Add solvent slowly, swirl gently and check for complete clarity.
- Store solutions at 2–8 °C; avoid freeze–thaw (storage guide).
- Calculate concentrations with the peptide reconstitution calculator; general method in how to reconstitute peptides.
Open questions
- How does the balance between amylin receptor and calcitonin receptor activity contribute to cagrilintide’s effects?
- What is the long-term profile of combined amylin and GLP-1 receptor agonism compared with either alone?
- How physically stable is reconstituted research-grade cagrilintide over weeks at 2–8 °C, given amylin’s tendency to aggregate?
For laboratory work, these questions mean that clarity checks after reconstitution and conservative in-use periods are especially important for cagrilintide.
Related research
Frequently asked questions
What is cagrilintide?
Cagrilintide is a synthetic, lipidated analogue of the pancreatic hormone amylin, developed by Novo Nordisk for once-weekly administration. It acts as a non-selective agonist of amylin and calcitonin receptors.
What does cagrilintide do?
Amylin is a satiety hormone co-secreted with insulin. In a phase 2 trial, once-weekly cagrilintide produced dose-related reductions in body weight compared with placebo over 26 weeks.
Why was cagrilintide developed instead of using pramlintide?
The existing amylin analogue pramlintide requires injections three times daily because of its short half-life. Native amylin is also highly prone to forming amyloid fibrils. Cagrilintide was designed to be stable and long-acting.
What is CagriSema?
CagriSema is the co-administration of cagrilintide with the GLP-1 receptor agonist semaglutide, studied in clinical trials to combine amylin and GLP-1 pathways.
What is cagrilintide's molecular weight?
About 4409 g/mol (C194H312N54O59S2) according to PubChem.
References
- Kruse T, et al. Development of Cagrilintide, a Long-Acting Amylin Analogue. J Med Chem. 2021. PMID: 34288673 https://pubmed.ncbi.nlm.nih.gov/34288673/
- Lau 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. 2021. PMID: 34798060 https://pubmed.ncbi.nlm.nih.gov/34798060/
- Frias 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. 2023. PMID: 37364590 https://pubmed.ncbi.nlm.nih.gov/37364590/
- PubChem Compound Summary for CID 171397054, Cagrilintide. National Center for Biotechnology Information. https://pubchem.ncbi.nlm.nih.gov/compound/171397054
- Müller TD, et al. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019. PMID: 31767182 https://pubmed.ncbi.nlm.nih.gov/31767182/
For laboratory research use only. The compounds discussed are not approved for human or veterinary use and are not drugs, foods or cosmetics. This article summarises published research and is not medical advice.
Sources
- Kruse T, et al. Development of Cagrilintide, a Long-Acting Amylin Analogue. J Med Chem. 2021. PMID: 34288673
- Lau 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. 2021. PMID: 34798060
- Frias 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. 2023. PMID: 37364590
- PubChem Compound Summary for CID 171397054, Cagrilintide. National Center for Biotechnology Information.
- Müller TD, et al. Glucagon-like peptide 1 (GLP-1). Mol Metab. 2019. PMID: 31767182