Sitagliptin

Class Oral hypoglycaemic
Chemistry

Dipeptidyl peptidase (DPP-4) inhibitor

Routes of administration

Oral only

Absorption

Completely absorbed, oral bioavailability 87%

Solubility

pKa=8.7; good water solubility

Distribution

VOD= 3-4 L/kg; 38% protein bound

Metabolism

Hepatic metabolism plays a minor role in the elimination

Elimination

79% excreted renally as unchanged drug

Time course of action

Half life 8-14 hrs

Target receptor

Dipeptidyl peptidase (DDP-4), an endothelial enzyme that normal breaks down regulatory peptides glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1(GLP-1).

Mechanism of action

By decreasing the degradation of GLP-1, DPP-4 inhibitors produce an increase in insulin secretion. GLP-1 binds to its G-protein-coupled receptors on pancreatic β-cells, where it increases intracellular cAMP, and therefore the availability of intracellular calcium that drives insulin exocytosis

Clinical effects

Hypoglycaemia, but also:
- headache
- nasopharyngitis

Literature reference

Baetta & Corsini (2011).

CICM details of understanding Not specifically listed in the CICM syllabus
Mentioned around Deranged Physiology
Related SAQs