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Dipeptidyl peptidase‐4 inhibitors and preservation of pancreatic islet‐cell function: a critical appraisal of the evidence
Author(s) -
van Genugten R. E.,
van Raalte D. H.,
Diamant M.
Publication year - 2012
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2011.01473.x
Subject(s) - incretin , islet , postprandial , medicine , dipeptidyl peptidase 4 , endocrinology , glucokinase , dipeptidyl peptidase , glucagon like peptide 1 , insulin , type 2 diabetes mellitus , type 2 diabetes , glucagon , vildagliptin , diabetes mellitus , biology , enzyme , biochemistry
Type 2 diabetes mellitus (T2DM) develops as a consequence of progressive β ‐cell dysfunction in the presence of insulin resistance. None of the currently‐available T2DM therapies is able to change the course of the disease by halting the relentless decline in pancreatic islet cell function. Recently, dipeptidyl peptidase (DPP)‐4 inhibitors, or incretin enhancers, have been introduced in the treatment of T2DM. This class of glucose‐lowering agents enhances endogenous glucagon‐like peptide 1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) levels by blocking the incretin‐degrading enzyme DPP‐4. DPP‐4 inhibitors may restore the deranged islet‐cell balance in T2DM, by stimulating meal‐related insulin secretion and by decreasing postprandial glucagon levels. Moreover, in rodent studies, DPP‐4 inhibitors demonstrated beneficial effects on (functional) β ‐cell mass and pancreatic insulin content. Studies in humans with T2DM have indicated improvement of islet‐cell function, both in the fasted state and under postprandial conditions and these beneficial effects were sustained in studies with a duration up to 2 years. However, there is at present no evidence in humans to suggest that DPP‐4 inhibitors have durable effects on β ‐cell function after cessation of therapy. Long‐term, large‐sized trials using an active blood glucose lowering comparator followed by a sufficiently long washout period after discontinuation of the study drug are needed to assess whether DPP‐4 inhibitors may durably preserve pancreatic islet‐cell function in patients with T2DM.