An update on the clinical pharmacology of the dipeptidyl peptidase 4 inhibitor alogliptin used for the treatment of type 2 diabetes mellitus

Clin Exp Pharmacol Physiol. 2015 Dec;42(12):1225-38. doi: 10.1111/1440-1681.12469.

Abstract

Alogliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor that is a class of relatively new oral hypoglycaemic drugs used in patients with type 2 diabetes (T2DM), can be used as monotherapy or in combination with other anti-diabetic agents, including metformin, pioglitazone, sulfonylureas and insulin with a considerable therapeutic effect. Alogliptin exhibits favorable pharmacokinetic and pharmacodynamic profiles in humans. Alogliptin is mainly metabolized by cytochrome P450 (CYP2D6) and CYP3A4. Dose reduction is recommended for patients with moderate or worse renal impairment. Side effects of alogliptin include nasopharyngitis, upper-respiratory tract infections and headache. Hypoglycaemia is seen in about 1.5% of the T2DM patients. Rare but severe adverse reactions such as acute pancreatitis, serious hypersensitivity including anaphylaxis, angioedema and severe cutaneous reactions such as Stevens-Johnson syndrome have been reported from post-marketing monitoring. Pharmacokinetic interactions have not been observed between alogliptin and other drugs including glyburide, metformin, pioglitazone, insulin and warfarin. The present review aimed to update the clinical information on pharmacodynamics, pharmacokinetics, adverse effects and drug interactions, and to discuss the future directions of alogliptin.

Keywords: DPP-4 inhibitor; adverse effect; alogliptin; combination therapy; pharmacokinetics; type 2 diabetes (T2DM).

Publication types

  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl Peptidase 4 / metabolism*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacokinetics
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Drug Interactions
  • Humans
  • Piperidines / adverse effects
  • Piperidines / pharmacokinetics
  • Piperidines / pharmacology*
  • Piperidines / therapeutic use
  • Uracil / adverse effects
  • Uracil / analogs & derivatives*
  • Uracil / pharmacokinetics
  • Uracil / pharmacology
  • Uracil / therapeutic use

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Piperidines
  • Uracil
  • Dipeptidyl Peptidase 4
  • alogliptin