Cagrilintide is a long-acting, lipidated analog of the pancreatic hormone amylin, developed by Novo Nordisk. It is a 37-residue peptide with an N-terminal C20 fatty diacid attached through a γ-glutamic acid linker, and it activates both amylin receptors and the calcitonin receptor without strong preference between them. It is investigational: it has been studied alone and as CagriSema, a fixed combination with semaglutide that is under FDA review, and it was not approved anywhere at the time of writing.
This profile covers amylin biology at the receptor level, the structural choices that turned a fibril-prone hormone into a stable reagent, what human trials have measured, and how cagrilintide is handled in the lab. It does not cover use in people or animals. In the Anhydrolabs catalog, it is listed as Cagrilintide.
Cagrilintide at a glance
| Property | Value |
|---|---|
| Name | Cagrilintide (INN) |
| Developer | Novo Nordisk |
| Class | Acylated amylin analog; amylin receptor and calcitonin receptor agonist |
| Main chain length | 37 amino acids, C-terminal amide |
| Parent molecule | Human amylin (islet amyloid polypeptide) |
| Disulfide bond | Cys2 to Cys7 |
| Lipidation | N-terminal C20 fatty diacid (19-carboxynonadecanoyl) through γ-Glu |
| Molecular formula | C194H312N54O59S2 |
| Molecular weight | About 4409 g/mol (PubChem) |
| CAS number | 1415456-99-3 |
| PubChem CID | 171397054 |
| Reported half-life in humans | 159 to 195 hours (Phase 1b) |
| Regulatory status | Investigational; combination with semaglutide submitted to the FDA in December 2025 |
Amylin: the parent hormone
Amylin, also called islet amyloid polypeptide (IAPP), is a 37-amino-acid peptide co-secreted with insulin by pancreatic β-cells. UniProt entry P10997 gives the mature human sequence:
KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY-NH2
It has a disulfide bond between Cys2 and Cys7 and an amidated C-terminal tyrosine. Human amylin is notorious in the lab for one reason: it forms amyloid fibrils readily in solution. The 2021 cagrilintide discovery paper names this "high propensity toward the formation of amyloid fibrils" as the central obstacle to making a usable analog.
The approved amylin analog pramlintide (Symlin) addressed fibril formation by replacing three residues with proline. According to its FDA label, pramlintide swaps Ala25, Ser28 and Ser29 for proline. The label gives its half-life as approximately 48 minutes, because it carries no albumin-binding group and about 40% circulates unbound. Cagrilintide keeps pramlintide's proline strategy and adds half-life extension.
Structure: what was changed and why
The published name of cagrilintide, as recorded in PubChem, spells out its full structure: an N-(19-carboxy-1-oxononadecyl) group, which is a C20 diacid, attached to γ-glutamic acid, which is joined to the N-terminal lysine of a 37-residue chain with a C-terminal prolinamide and a Cys2 to Cys7 disulfide.
Aligned against human amylin, cagrilintide differs at six positions:
| Position | Human amylin | Cagrilintide | Likely role |
|---|---|---|---|
| 14 | Asn | Glu | Removes an asparagine that can deamidate; adds negative charge |
| 17 | Val | Arg | Adds positive charge in the helical region |
| 25 | Ala | Pro | Anti-fibril proline, as in pramlintide |
| 28 | Ser | Pro | Anti-fibril proline, as in pramlintide |
| 29 | Ser | Pro | Anti-fibril proline, as in pramlintide |
| 37 | Tyr | Pro (amide) | C-terminal change recorded in the PubChem structure for cagrilintide |
The "likely role" column for positions 14 and 17 is our reading of the chemistry rather than a statement from the discovery paper, which describes a broad structure-activity campaign. Cagrilintide was compound 23 in that series. The three prolines at 25, 28 and 29 break up the β-sheet-prone segment that drives amylin aggregation.
The lipid chain
Unlike semaglutide or tirzepatide, which acylate a lysine side chain partway along the peptide, cagrilintide carries its fatty diacid at the N-terminus. The C20 diacid binds serum albumin, which is what extends its half-life from under an hour (pramlintide) to about a week. In the Phase 1b trial run with semaglutide, cagrilintide showed a half-life of 159 to 195 hours, roughly 6.6 to 8.1 days, across the range studied.
Albumin binding also matters in vitro. A 2025 study from Eli Lilly showed that adding 1% human serum albumin reduced cagrilintide's measured potency at human amylin and calcitonin receptors, while non-lipidated rat amylin and salmon calcitonin were unaffected.
Receptor pharmacology
Amylin does not have a single dedicated receptor gene. Its receptors are heterodimers of the calcitonin receptor (CTR, gene CALCR, UniProt P30988) with one of three receptor activity-modifying proteins (RAMPs):
| Receptor | Composition | Also activated by |
|---|---|---|
| AMY1 | CTR + RAMP1 | Amylin |
| AMY2 | CTR + RAMP2 | Amylin |
| AMY3 | CTR + RAMP3 | Amylin |
| CTR | Calcitonin receptor alone | Calcitonin |
All are class B GPCRs that couple to Gs and raise cyclic AMP, the same family as the GLP-1 receptor covered in our GLP-1 receptor agonist primer.
Cagrilintide is described as a non-selective agonist. It activates the amylin receptors and the calcitonin receptor without strong preference. That property is the main point of contrast with eloralintide, a later amylin analog from Eli Lilly that was designed to favor AMY1 over CTR. For assay design, this means cagrilintide will produce a cAMP signal in cells expressing CTR alone, and its activity cannot be read as amylin-receptor-specific unless RAMP expression is controlled.
A practical note: many common cell lines express one or more RAMPs endogenously. When characterizing an amylin analog, confirm which RAMPs your line expresses, or use a RAMP-null background with defined transfections.
Research context and trial status
Novo Nordisk developed cagrilintide for obesity. In animal work and human trials, it has been studied alone and together with semaglutide, the GLP-1 receptor agonist. The rationale is that amylin receptors and GLP-1R are distinct systems.
Human trials registered on ClinicalTrials.gov include:
| Phase | Registry number | Design |
|---|---|---|
| Phase 1b | NCT03600480 | Cagrilintide with semaglutide in adults with overweight or obesity; safety and pharmacokinetics |
| Phase 2 | NCT03856047 | Cagrilintide alone versus placebo and liraglutide over 26 weeks |
| Phase 3 (REDEFINE 1) | NCT05567796 | CagriSema in adults with obesity or overweight |
| Phase 3 (REDEFINE 2) | NCT05394519 | CagriSema in adults with type 2 diabetes and overweight or obesity |
| Phase 3 (RENEW 1) | NCT07220642 | Cagrilintide alone in adults with overweight or obesity |
The Phase 2 trial, published in the Lancet in 2021, used percentage change in body weight at 26 weeks as its primary end point. We list what trials measured, not their findings.
On December 18, 2025, Novo Nordisk announced that it had submitted a New Drug Application to the FDA for CagriSema, supported by REDEFINE 1 and REDEFINE 2. At the time of writing, the FDA had not announced a decision, and cagrilintide itself is not approved as a standalone product anywhere.
Cagrilintide in combination reagents
The catalog lists cagrilintide alone and in a Retatrutide / Cagrilintide blend with retatrutide, the investigational GIP, GLP-1 and glucagon receptor agonist described in what is retatrutide. The blend pairs an amylin-family ligand with a glucagon-family ligand at a fixed ratio. That is convenient for co-stimulation experiments, but it cannot separate the two components. Use single-compound vials when each ligand has to be titrated independently.
Laboratory handling
Cagrilintide combines two properties that call for care: an amylin backbone with some aggregation tendency, and a lipid chain that binds surfaces and proteins. The certificate of analysis for your lot takes precedence over these general notes.
- Storage of the powder. Keep the sealed vial at −20 °C or colder, dry and protected from light, and warm it to room temperature before opening. Our guide to storing peptides explains why moisture is the main risk to lyophilized material.
- Reconstitution. Dissolve in a slightly basic aqueous buffer. The C20 diacid and the acidic residues carry negative charge above neutral pH, which helps the peptide go into solution. Add solvent down the vial wall and swirl gently rather than vortexing, since agitation promotes aggregation of amyloidogenic sequences. Our walkthrough of reconstituting lyophilized peptides covers the concentration arithmetic.
- Keep the disulfide intact. Cys2 and Cys7 form a ring that is part of the pharmacophore. Do not add reducing agents such as DTT or TCEP to stock solutions, and avoid strongly basic buffers held for long periods, which encourage thiol exchange.
- Surfaces and aggregation. Use low-binding tubes and tips. Prepare working dilutions fresh, inspect solutions for haze, and centrifuge before use if anything is visible. Aggregates give irreproducible potency values.
- Aliquots. Freeze single-use aliquots and avoid repeated freezing and thawing.
- Analytics. Reversed-phase HPLC and a mass spectrum matching the expected formula weight are the two checks that matter most. Peptides with a free thiol from a broken disulfide often show as a separate signal close to the main component.
Anhydrolabs supplies cagrilintide as a lyophilized powder in vacuum-sealed vials and as 10-vial kits, with a certificate of analysis for each lot. All material is for laboratory research only; see research use and storage and handling.
What is still unknown
The discovery paper describes the structure-activity work that produced cagrilintide but does not publish a full receptor selectivity panel of the kind now reported for newer amylin analogs. Structural biology on amylin receptors is also younger than the equivalent work on GLP-1R, since a CTR-RAMP complex is harder to prepare than a single receptor. For researchers, that means selectivity claims about any amylin analog should be read together with the exact receptor composition and cell background used.
