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Compound Evidence InstituteEvidence synthesis · established 2023Graded assessments of compounds, trials, methods and supply
Document set current to 30 July 2026
Compound monograph · §2

Lixisenatide — pharmacology

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

Document identifier
CEI-MN-010/2
Series
Compound monograph
Version
3.1
Published
12 Oct 2024
Last reviewed
12 Apr 2025
Next review
12 Apr 2027
Identifier
10.71829/cei.mono.10
Certainty
Moderate
Cycle
2024 Q4

§2Pharmacology

§2.1Molecular targets

Table 2. Molecular targets recorded for Lixisenatide, with the character of the interaction and the potency where the Institute holds it.

TargetInteractionNote
GLP-1 receptor (GLP1R)Full agonistAffinity approximately four-fold higher than native GLP-1

§2.2Mechanism of action

A short-acting prandial GLP-1 receptor agonist. Its dominant pharmacodynamic effect is marked slowing of gastric emptying, which produces substantial postprandial glucose reduction with comparatively modest effects on fasting glucose and HbA1c. This makes it mechanistically complementary to basal insulin, which is the basis of the fixed-combination products.[1,2]

§2.3Pharmacokinetics

Terminal half-life
≈3 h
Time to maximum concentration
1–3.5 h
Volume of distribution
≈100 L
Plasma protein binding
≈55 %
Clearance
≈35 L/h
Bioavailability
not formally reported

Glomerular filtration with proteolytic degradation. Exposure rises with declining renal function and use is not recommended below an eGFR of 15 mL/min/1.73 m².

Reconstructed plasma concentration–time profilePlasma concentration plotted against time after dosing, reconstructed from published pharmacokinetic parameters.0.00.20.40.60.8024681012Time after first dose (hours)Relative concentrationt max ≈ 1 ht½ ≈ 3 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

  • Oral medicines requiring rapid absorption — administer at least 1 hour before lixisenatide
  • Sulfonylureas and basal insulin — hypoglycaemia

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. Pfeffer MA, Claggett B, Diaz R, Dickstein K, Gerstein HC, Køber LV, Lawson FC, Ping L, Wei X, Lewis EF, Maggioni AP, McMurray JJV, Probstfield JL, Riddle MC, Solomon SD, Tardif JC. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. New England Journal of Medicine 2015;373(23):2247–2257. doi:10.1056/NEJMoa1509225 · PMID 26630143
  2. Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metabolism 2018;27(4):740–756. doi:10.1016/j.cmet.2018.03.001 · PMID 29617641

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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