title: Dipeptidyl peptidase-IV inhibitors: a major new class of oral antidiabetic drug.
abstract: Exploiting the incretin effect to develop new glucose-lowering treatments has become the focus of intense research. One successful approach has been the development of oral inhibitors of dipeptidyl peptidase-IV (DPP-IV). These drugs reversibly block DPP-IV-mediated inactivation of incretin hormones, for example, glucagon-like peptide 1 (GLP-1) and also other peptides that have alanine or proline as the penultimate N-terminal amino acid. DPP-IV inhibitors, therefore, increase circulating levels and prolong the biological activity of endogenous GLP-1, but whether this is sufficient to fully explain the substantial reduction in haemoglobin A(1c) (HbA(1c)) and associated metabolic profile remains open to further investigation. DPP-IV inhibitors such as vildagliptin and sitagliptin have been shown to be highly effective antihyperglycaemic agents that augment insulin secretion and reduce glucagon secretion via glucose-dependent mechanisms. This review summarizes the major clinical trials with DPP-IV inhibitors as monotherapy and as add-on therapy in patients with type 2 diabetes. The magnitude of HbA(1c) reduction with DPP-IV inhibitors depends upon the pretreatment HbA(1c) values, but there seems to be no change in body weight, and very low rates of hypoglycaemia and gastrointestinal disturbance with these agents. DPP-IV inhibitors represent a major new class of oral antidiabetic drug and their metabolic profile offers a number of unique clinical advantages for the management of type 2 diabetes.
authors.affiliation: Department of Diabetes and Endocrinology, Sherwood Forest Hospitals NHS Trust, Mansfield, UK. richard.donnelly@nottingham.ac.uk
authors.forename: Iskandar
authors.initials: I
authors.lastname: Idris
authors.forename: Richard
authors.initials: R
authors.lastname: Donnelly
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018849:Controlled Clinical Trials as Topic; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000201:enzymology; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D051379:Mice; D011480:Protease Inhibitors / Q000627:therapeutic use*; D051381:Rats
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents; D011480:Protease Inhibitors; D018819:Dipeptidyl Peptidase 4