title: Sitagliptin: Profile of a novel DPP-4 inhibitor for the treatment of type 2 diabetes.
abstract: Novel therapeutic strategies for type 2 diabetes are needed, since the current treatment options neither address all pathophysiological mechanisms nor achieve the glycemic target goals. A general islet-cell dysfunction including insulin- and glucagon-secretion defects contributes to the pathophysiology of type 2 diabetes. Improving islet function by incretin hormone action is a novel therapeutic approach. Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) are important incretin hormones contributing to 50-70% of the stimulation of insulin secretion after a meal. Dipeptidyl-peptidase IV (DPP-4) inhibitors inhibit the degradation of GLP-1 and GIP as well as that of other regulatory peptides. Sitagliptin, a DPP-4 inhibitor, is orally active and has been shown to be efficacious and safe in clinical studies. Sitagliptin has received approval in Mexico, the United States and other countries. Like other DPP-4 inhibitors, sitagliptin reduces hemoglobin A1c (HbA1c), fasting and postprandial glucose by glucose-dependent stimulation of insulin secretion and inhibition of glucagon secretion. Sitagliptin is weight neutral. Indirect measures show a possible improvement of beta-cell function. Sitagliptin does not cause a higher rate of hypoglycemia in comparison to metformin or placebo. This article gives an overview of the mechanisms of action, pharmacology and clinical trial results of sitagliptin.
authors.affiliation: Department of Medicine IV, Eberhard-Karls-University, Tübingen, Germany. baptist.gallwitz@med.uni-tuebingen.de
authors.forename: Baptist
authors.initials: B
authors.lastname: Gallwitz
mesh_terms: D058892:Adenosine Deaminase Inhibitors; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D006023:Glycoproteins / Q000037:antagonists & inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000187:drug effects; D011719:Pyrazines / Q000494:pharmacology* / Q000627:therapeutic use*; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D058892:Adenosine Deaminase Inhibitors; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006023:Glycoproteins; D007004:Hypoglycemic Agents; D011719:Pyrazines; D014230:Triazoles; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4; D000068900:Sitagliptin Phosphate