Impact of DPP4 inhibition on incretin effect

In recent years, inhibitors of the ubiquitous enzyme dipeptidyl peptidase 4 (DPP4), have been developed for the treatment of type 2 diabetes. Under normal circumstances, DPP4  degrades and inactivates the insulinotropic gut incretin hormones:  glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP1). The incretin effect leading to an increase in plasma insulin levels following oral glucose load is thought to be dependent on the incretin hormone levels. These hormones are secreted in response to meal ingestion and are rapidly terminated by DPP4-induced degradation.

Rhee et al. investigated the impact of DPP4 inhibition on the incretin effect  in healthy, normal-glucose tolerant subjects. They also studied the impact of DPP4 inhibitor-induced elevations of plasma levels of active incretin hormones on gastric emptying and gastrointestinal-mediated glucose disposal (GIGD).

Their study shows that  elevated plasma levels of intact active incretin hormones (attained through ‘acute’ inhibition of DPP4) have no effect on incretin effect, fasting plasma glucose, glucose tolerance, GIGD, glucagon responses to oral or i.v. glucose or gastric emptying following OGTT in healthy subjects.

Read full article at Rhee et al. European Journal of Endocrinology 171 (3) 353-362. DOI: 10.1530/EJE-14-0314