Dipeptidyl peptidase 4 inhibition with sitagliptin: a new therapy for type 2 diabetes

Expert Opin Investig Drugs. 2007 Apr;16(4):533-45. doi: 10.1517/13543784.16.4.533.

Abstract

Sitagliptin is a once-daily, orally active, competitive and fully reversible inhibitor of dipeptidyl peptidase 4, the enzyme that is responsible for the rapid degradation of the incretin hormone glucagon-like peptide-1. It is the first in this new class of antihyperglycaemic agents to gain regulatory approval for the treatment of Type 2 diabetes, both as a monotherapy and for use in combination with metformin or a thiazolidinedione. In clinical trials of < or = 1-year duration, sitagliptin improves glycaemic control by reducing both fasting and postprandial glucose concentrations, leading to clinically meaningful reductions in glycosylated haemoglobin levels. It is safe and well tolerated, with a side-effect profile that is similar to that of the placebo, a low incidence of hypoglycaemia and body weight neutrality. Further clinical experience with sitagliptin will reveal its long-term durability, safety and efficacy.

Publication types

  • Review

MeSH terms

  • Adenosine Deaminase / metabolism
  • Adenosine Deaminase Inhibitors*
  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / enzymology*
  • Dipeptidyl Peptidase 4 / metabolism
  • Dipeptidyl-Peptidase IV Inhibitors*
  • Drugs, Investigational / pharmacology
  • Drugs, Investigational / therapeutic use*
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Glycoproteins / antagonists & inhibitors*
  • Glycoproteins / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology
  • Hypoglycemic Agents / therapeutic use
  • Pyrazines / pharmacology
  • Pyrazines / therapeutic use*
  • Sitagliptin Phosphate
  • Triazoles / pharmacology
  • Triazoles / therapeutic use*

Substances

  • Adenosine Deaminase Inhibitors
  • Dipeptidyl-Peptidase IV Inhibitors
  • Drugs, Investigational
  • Enzyme Inhibitors
  • Glycoproteins
  • Hypoglycemic Agents
  • Pyrazines
  • Triazoles
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • Adenosine Deaminase
  • Sitagliptin Phosphate