Cagrilintide Explained: The Long-Acting Amylin Analogue and Its Early Trials

Amylin is a pancreatic hormone that induces satiety, and cagrilintide is a long-acting analogue of it (Lau 2021). That makes it the odd one out among the incretin-style peptides covered here: it targets the amylin pathway rather than GLP-1 alone. This Vial Post explainer reviews the structure listed in PubChem and how its first published trials were designed.

Nothing here is guidance on use in people or animals. The Vial Post covers cagrilintide only as a subject of laboratory and literature research.

At a Glance

• Class: long-acting amylin analogue (Lau 2021; Enebo 2021).
• Formula and mass: PubChem gives C194H312N54O59S2 and a molecular weight of about 4409 g/mol under CID 171397054 (PubChem: Cagrilintide).
• Structure notes: the PubChem systematic name describes an N-terminal 19-carboxynonadecanoyl (fatty diacid) group, a C-terminal prolinamide and a cyclic (3->8) disulfide (PubChem: Cagrilintide).
• Identifiers: CAS number 1415456-99-3 and the code NN0174-0833 (PubChem: Cagrilintide).

The two sulfur atoms in the formula belong to the cysteines that form that disulfide ring.

Phase 1b With Semaglutide

Enebo and colleagues ran a randomised, placebo-controlled, multiple-ascending-dose phase 1b trial at a single US centre (NCT03600480). Adults aged 18 to 55 with a BMI of 27.0 to 39.9 who were otherwise healthy were enrolled in six sequential overlapping cohorts and randomised 3:1 to once-weekly cagrilintide or placebo, each combined with once-weekly semaglutide. The primary endpoint was the number of treatment-emergent adverse events; pharmacokinetic and pharmacodynamic measures were secondary or exploratory. Ninety-six people were randomised (Enebo 2021).

Phase 2 Dose-Finding

Lau and colleagues ran a multicentre, randomised, double-blind, placebo-controlled and active-controlled phase 2 trial at 57 sites in ten countries (NCT03856047). It compared five once-weekly cagrilintide arms with once-daily liraglutide and placebo over a 26-week treatment period. The primary endpoint was percentage change in body weight from baseline to week 26 (Lau 2021).

The authors reported greater weight reduction than placebo in every cagrilintide arm, and named gastrointestinal disorders and administration-site reactions as the most frequent adverse events (Lau 2021). The Vial Post does not restate administered amounts; see the primary papers below.

Reader Questions

Is cagrilintide a GLP-1 drug? No. It is described as an amylin analogue; semaglutide was the GLP-1 analogue it was paired with in the phase 1b study (Enebo 2021).

Why the fatty acid chain? PubChem's name shows a long-chain diacid on the N-terminus (PubChem: Cagrilintide). The trial papers call cagrilintide long-acting, and it was given once weekly (Lau 2021).

Who funded the phase 2 trial? Novo Nordisk A/S is listed as the funder (Lau 2021).

Lab Note

With a disulfide bridge and a lipid group, cagrilintide's identity check should rely on mass spectrometry, with HPLC for purity. Our explainers on HPLC versus mass spec and reading a Certificate of Analysis cover both.

For research and educational use only. This article is not medical advice and does not describe dosing or human use.