A Different Hormone Family Entirely
Cagrilintide is routinely filed alongside the incretin analogues and routinely misdescribed as one. It is not. Amylin is a separate pancreatic hormone, co-secreted with insulin by β-cells, and it signals through amylin and calcitonin receptors — a different receptor family from GLP-1, GIP and glucagon.
That is the whole point of the CagriSema pairing. Combining cagrilintide with semaglutide is not combining two incretins; it is combining two unrelated satiety signals, which is a genuinely different proposition from pairing GLP-1 with GIP or with glucagon.
Why Native Amylin Could Not Be Used
Human amylin has a practical problem: it aggregates into β-sheet amyloid fibrils readily and quickly. Amyloid deposits of islet amyloid polypeptide — amylin's other name — are a recognised feature of type 2 diabetic pancreatic tissue. A peptide that does that cannot be formulated as a long-acting agent.
Kruse and colleagues addressed it with a set of substitutions, reported in the Journal of Medicinal Chemistry in 2021. Prolines at positions 25, 28 and 29, borrowed from rat amylin — which does not fibrillate — suppress β-sheet formation. Substitutions at 14 and 17 create a salt bridge that stabilises the central helix. A C-terminal proline change improves potency, particularly at the calcitonin receptor. An eicosanedioic (C20) diacid is conjugated at the N-terminal lysine through a γGlu linker for albumin binding.
The result, compound 23 in that paper, is cagrilintide: a 37-residue core with a Cys–Cys disulfide, a C-terminal amide and a half-life measured in days rather than minutes.
Amylin and Calcitonin Receptors Together
Cagrilintide is described as a non-selective agonist at amylin (AMY) and calcitonin (CT) receptors. Calcitonin-receptor engagement is part of its reported pharmacology rather than an off-target liability — and that is not an accident of the chemistry, since amylin receptors are themselves calcitonin receptors complexed with receptor activity-modifying proteins.
For experimental design that matters: an assay system expressing calcitonin receptors without the modifying proteins will report cagrilintide activity, but not amylin-receptor activity. Knowing which complex your system presents is the difference between a meaningful result and an uninterpretable one.
The Sequence Nobody Has Published
There is no reliably published one-letter sequence for cagrilintide. Vendor pages that appear to give one are usually quoting native human amylin — KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY — which lacks every substitution that makes cagrilintide what it is.
It is possible to reconstruct a plausible string by applying the published substitutions to the amylin backbone. We do not publish such a reconstruction as fact, and neither should a supplier. What is firmly established is CAS 1415456-99-3, formula C194H312N54O59S2 and a free-base mass of 4409.01 g/mol — and that the CAS number 1949357-25-1, which also circulates, does not appear in any primary source.
Sources also disagree on whether the disulfide is numbered Cys2–Cys7 or Cys3–Cys8. Both describe the same bond; the difference is whether the fatty-acid–γGlu unit is counted as residue 1.
What the Co-Formulation Looks Like
Our cagrilintide and semaglutide blend is co-lyophilised at 10 mg of each per 20 mg vial. Both components are acylated peptides with similar solubility behaviour, which is why they share a vial without difficulty.
They resolve separately under reverse-phase HPLC, so a batch certificate reports purity and content per component rather than one combined figure — worth checking when you look the lot up in the COA verification hub.
The practical limitation of any co-lyophilised blend is that the ratio is fixed at manufacture. If the contribution of one component is your question, single-compound vials are the right choice — semaglutide on its own is the obvious control.
Study-Design Notes
Do not use a GLP-1R assay. Cagrilintide will look inert, because it is — at that receptor. This is the most common way to waste a cagrilintide experiment.
Account for the salt form. Free base and acetate salt are both sold. The free base is C194H312N54O59S2 at 4409.01; acetate listings run around 4469.06. A molar calculation from the wrong one is off by more than a percent.
Treat aggregation as a live variable. The proline substitutions suppress fibrillation; they do not abolish the underlying tendency of the amylin fold. Avoid vortexing, avoid repeated freeze–thaw, and follow the handling in our peptide storage guide.
Reconstitute conservatively. Volumes and technique are in the peptide reconstitution guide; bacteriostatic water is the standard diluent.
Frequently Asked Questions
Is cagrilintide a GLP-1 analogue?
No. It is an amylin analogue and acts on amylin and calcitonin receptors, which are a different receptor family. It is frequently studied alongside semaglutide, a GLP-1 analogue, and the two are co-formulated as CagriSema — but the two compounds do unrelated things.
Why is there no published sequence?
Novo Nordisk has not released one. Kruse et al. (J Med Chem 2021;64:11183-94) describe the substitutions relative to human amylin — 14E, 17R, 25P, 28P, 29P, a C-terminal proline change and an N-terminal C20 fatty acid — without publishing the resulting string. Vendor pages that show a sequence are usually quoting native amylin.
What does the amylin arm add to a GLP-1?
A second, unrelated satiety signal. Amylin is co-secreted with insulin and acts through its own receptor family, so combining it with a GLP-1 agonist is mechanistically different from combining two incretins such as GLP-1 and GIP.
Which CAS number is correct?
1415456-99-3. The number 1949357-25-1 also circulates but does not appear in primary sources. Confirm against the batch certificate rather than a catalog listing.
References & Further Reading
Kruse T et al., J Med Chem 2021;64:11183-11194; Lau DCW et al., Lancet 2021; Enebo LB et al., Lancet 2021; Westermark P et al., Physiol Rev 2011 (islet amyloid polypeptide).