Dipeptidyl peptidase-IV inhibitors can restore glucose homeostasis in type 2 diabetics via incretin enhancement.
Incretin levels approach normal physiological values following treatment with dipeptidyl peptidase (DPP)-IV inhibitors. This is in contrast to incretin levels resulting from the exogenous administration of glucagon-like peptide (GLP)-1 and its analogs, which can reach super-physiological values. This review describes the role of DPP-IV inhibitors as incretin enhancers in the regulation of glucose homeostasis in type 2 diabetic patients. The roles of incretins and the effect of DPP-IV on their actions are described, as are new therapeutic interventions based on the restoration of impaired incretin secretion in type 2 diabetic patients and obese individuals. In addition, the relevance of DPP-IV inhibition for weight control, its potential influence on beta-cell mass, and possible new indications are discussed, as are the implications of the currently available clinical data.
Mest
Hans-Juergen
HJ
Lilly Forschung GmbH, Lilly Research Laboratories, Essener Bogen 7, 22419 Hamburg, Germany. hj.mest@t-online.de
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001835:Body Weight / Q000187:drug effects; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D005749:Gastric Inhibitory Polypeptide / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000473:pathology; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*
D001786:Blood Glucose; D011480:Protease Inhibitors; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4