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Document set current to 30 July 2026
Compound monograph · §2

CagriSema (cagrilintide with semaglutide) — pharmacology

Molecular targets, mechanism of action, pharmacokinetics and interactions as characterised in humans.

Document identifier
CEI-MN-006/2
Series
Compound monograph
Version
4.1
Published
24 May 2024
Last reviewed
24 Feb 2025
Next review
24 Feb 2027
Identifier
10.71829/cei.mono.6
Certainty
Moderate
Cycle
2024 Q2

§2Pharmacology

§2.1Molecular targets

Table 2. Molecular targets recorded for CagriSema (cagrilintide with semaglutide), with the character of the interaction and the potency where the Institute holds it.

TargetInteractionNote
GLP-1 receptor (GLP1R)Full agonist (semaglutide component)See semaglutide monograph
Amylin and calcitonin receptorsAgonist (cagrilintide component)See cagrilintide monograph

§2.2Mechanism of action

The combination pairs two complementary satiation mechanisms: GLP-1 receptor agonism acting on hypothalamic and hindbrain appetite circuits, and amylin receptor agonism acting principally at the area postrema to promote meal termination. Preclinical and early clinical data suggest additive rather than merely overlapping effects on energy intake.[1,2]

§2.3Pharmacokinetics

Terminal half-life
≈7 days for both components
Time to maximum concentration
1–3 days
Volume of distribution
as for each component
Plasma protein binding
>99 % for both
Clearance
as for each component
Bioavailability
as for each component

Each component follows its own route; no clinically significant pharmacokinetic interaction between the two has been reported.

Reconstructed plasma concentration–time profilePlasma concentration plotted against time after dosing, reconstructed from published pharmacokinetic parameters.0.00.51.01.50200400600800Time after first dose (hours)Relative concentrationt max ≈ 555 ht½ ≈ 168 h
Modelled profileSimulated observationsDose administration
Figure 2. Illustrative. Plasma concentration–time profile reconstructed by the Institute from the published half-life and time-to-maximum-concentration parameters using a one-compartment model with first-order absorption. The curve is not digitised from a published figure and its vertical scale is relative. It is published to convey the shape of the profile and the approach to steady state, not to supply a concentration at any time point.

§2.4Interactions

  • As for each component

References cited on this page

References are numbered in order of first citation in this document. Each superscript in the text links to its entry below.

  1. Frías JP, Deenadayalan S, Erichsen L, Knop FK, Lingvay I, Macura S, Mathieu C, Pedersen SD, Davies M. 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. The Lancet 2023;402(10403):720–730. doi:10.1016/S0140-6736(23)01163-7 · PMID 37364591
  2. Lau DCW, Erichsen L, Francisco AM, Satylganova A, le Roux CW, McGowan B, Pedersen SD, Pietiläinen KH, Rubino DM, Batterham RL. 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. The Lancet 2021;398(10317):2160–2172. doi:10.1016/S0140-6736(21)01751-7 · PMID 34798060

Identifiers are reproduced only where the Institute holds them. Where a digital object identifier or PubMed identifier is not shown, the Institute has recorded the journal and year and has not constructed an identifier.

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