Objective: Pharmacologic inhibition with the dipeptidyl peptidase 4 (DPP-4) inhibitor, vildagliptin, prolongs the action of endogenously secreted incretin hormones leading to improved glycemic control in patients with type 2 diabetes mellitus (T2DM). We undertook a double-blinded, randomized-order, cross-over study to examine the vildagliptin mechanisms of action on islet function and glucose utilization.

Research Design and Methods: Participants with T2DM (n = 16) who had a baseline hemoglobin A_1c (HbA_1c) of 7.1 ± 0.2%, completed a cross-over study with 6 weeks of treatment with vildagliptin and 6 weeks with placebo. At the completion of each arm, participants had a study of postprandial metabolism and a 2-step glucose clamp performed at 20 and 80 mU/min-m² insulin infusions (LO and HI).

Results: Vildagliptin increased postprandial glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) by 3-fold and 2-fold, respectively, reduced fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) by 1.3 ± 0.3 mmol/l and 1.6 ± 0.3 mmol/l (both P <0.01), and improved glucoseresponsiveness of insulin secretion by 50% (P <0.01). Vildagliptin lowered postprandial glucagon by 16% (P <0.01). Examined by glucose clamp, insulin sensitivity and glucose clearance improved following vildagliptin (P <0.01).

Conclusions: Vildagliptin improves islet function in T2DM and improves glucose metabolism in peripheral tissues.