Cagrilintide

peptide · endocrine · digestive · Subcutaneous

Cagrilintide, a peptide. Long-acting acylated amylin analogue — a 37-residue peptide with a cyclic 3-to-8 disulfide, a C-terminal… Subcutaneous half-life 6.6 d.

Long-acting acylated amylin analogue — a 37-residue peptide with a cyclic 3-to-8 disulfide, a C-terminal prolinamide, and a C20 fatty diacid on a gamma-Glu/Lys linker that binds albumin and is the designed half-life mechanism. Acts as a dual agonist at the amylin receptors (AMY1-3, calcitonin receptor core plus a RAMP) and at the calcitonin receptor itself, a class its developers call a DACRA. Amylin signalling slows gastric emptying and drives satiation through the area postrema, a mechanism ORTHOGONAL to GLP-1 — which is why it is developed as a partner for semaglutide rather than a competitor, and why the combination is more than additive on weight.

PubChem CID 171397054 (C194H312N54O59S2). ALL HUMAN PK IS COMBINATION PK — there is no cagrilintide monotherapy dataset in any indexed abstract. Enebo 2021 (PMID:33894838), phase 1b, six cohorts of 12 (11 at 4.5 mg), BMI 27.0-39.9, dosed once-weekly SC together with semaglutide 2.4 mg. HALF-LIFE 159 h is the LOWER ENDPOINT of the verbatim "Cagrilintide 0.16-4.5 mg had a half-life of 159-195 h", a range across dose groups; the endpoint rather than the midpoint, per the standing rule. ka 0.1525 /h IS A BACK-DERIVATION AND SAYS SO: it reproduces the verbatim lower-endpoint "median tmax of 24-72 h" against that half-life, by solving tmax = ln(ka/ke)/(ka-ke) with ke = ln2/159. It is authored rather than omitted because resolvePk would otherwise substitute 1.0 /h and put the peak of a once-weekly peptide at 5.4 h, 4 to 13x early. Two caveats travel with it: the Tmax is a median across dose groups, and it is a STEADY-STATE median, which is not exactly the single-dose quantity that formula inverts. NO VOLUME, AND THE REASON IS A DATE. The abstract prints Cmax 6.14-170 nmol/L and AUC0-168h 926-24 271 nmol*h/L, which look like one division from a V/F, but the PK endpoints were "assessed from day of last dose (week 19) to end of treatment (week 20)" — after 16 weeks of co-escalation and 4 weeks at target, so they are steady-state. At this half-life on a weekly interval the accumulation ratio is about 2, so the naive single-dose arithmetic (4.5 mg / 0.7495 mg/L = 6.0 L) and the accumulation-corrected version (about 12 L) differ twofold, and the abstract does not print what would settle it. A 2x fork is not a measurement. The record therefore runs on the 0.5 L/kg default of 35 L, which for an albumin-bound acylated peptide is likely 3-6x too high (semaglutide's measured total volume is 7.7 L) and makes concentrations read low; full text of the phase 1b would close it. MEASURED THROUGH THE SOLVER RATHER THAN ASSUMED: resolved through pkParamsForRoute and evaluated at a single 4.5 mg dose, this record peaks at 24 nmol/L at t = 24.006 h. The tmax confirms the ka does what it was derived to do. The peak is 7.1x below the 170 nmol/L the paper reports at that dose — but that published figure is STEADY-STATE, so roughly 2x of the gap is accumulation a single-dose curve is correct to omit, leaving about 3.5x attributable to the defaulted volume. That is the measured size of the missing V_L, and it points the same way as the 6-12 L estimate above. Clearance and volume are reported only as "similar across treatment groups", with no numbers. The renal and hepatic impairment study (PMID:42228334) publishes AUC RATIOS only. Kruse 2021 (PMID:34288673) is the discovery paper and its abstract carries no numeric cagrilintide PK at all — its only half-life belongs to pramlintide. SEARCH TRAP: PubMed auto-translates AM833 to fleroxacin and does not index NN9838; use the INN. Mechanism reference PMID:40847076 (cryo-EM of the AMY1R-Gs and CTR-Gs complexes).

Pharmacokinetics

Related compounds

Sources: PMID:33894838, PMID:34288673, PMID:40847076, PMID:42228334