Inhibition of DPP-4 with Vildagliptin Improved Insulin Secretion in Response to Oral as well as “Isoglycemic” Intravenous Glucose without Numerically Changing the Incretin Effect in Patients with Type 2 Diabetes

Abstract

DPP-4 inhibition augmented insulin secretory responses both after oral glucose and during isoglycemic iv glucose infusions, with no net change in the incretin effect. Thus, slight variations in basal incretin levels may be more important than previously thought. Or, DPP-4 inhibitor-induced change in the incretin-related environment of islets may persist overnight, augmenting insulin secretory responses to iv glucose as well. Alternatively, yet unidentified mediators of DPP-4 inhibition may have caused these effects.

Effects of Sitagliptin and Metformin Treatment on Incretin Hormone and Insulin Secretory Responses to Oral and “Isoglycemic” Intravenous Glucose

“…was given at 0 min. On day 6, 20% glucose was administered intravenously to copy the glycemic excursions obtained after the oral glucose ("isoglycemic" intravenous glucose infusion), as previously described (19). After basal blood specimens were drawn at -15 and 0 min, blood was taken at 15, 30, 45, 60, 90, 120, 180, and 240 min.…”

“…Therefore, it could be postulated that enhancement of endogenous intact incretin levels with DPP-4 inhibitors may ameliorate the defective incretin effect seen in type 2 diabetes. Despite the plausibility of this hypothesis, our previous study using vildagliptin treatment did not show any change in the numerical contribution of the incretin effect to insulin secretory responses after oral glucose challenges (19). A similar study, using mixed-meal stimulation of insulin secretion, also came to a similar conclusion (20).…”

“…Glucose, insulin, C-peptide, total GLP-1 (C-terminally directed assay), intact GLP-1 (sandwich ELISA), total GIP (C-terminally directed assay), intact GIP (N-terminally directed assay), and glucagon were determined as previously described (19).…”

“…Accordingly, it is possible that a combined treatment with metformin plus a DPP-4 inhibitor might result in a meaningful interaction at the level of L-cell (GLP-1) secretion. This was not explored in our previous study using vildagliptin treatment (19).…”

Liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the determination of Vildagliptin in rat plasma

“…The deactivation of DPP-4 is one of the currently used approaches for the treatment of type 2 diabetes [3,4]. Vildagliptin is a selective and reversible inhibitor of DPP-4: this inhibition of DPP-4 increases the levels of incretin hormones, resulting in a significant improvement of glucose homeostasis [5].…”