['To examine whether 12 weeks of treatment with a dipeptidyl peptidase-4 (DPP-4) inhibitor, sitagliptin, influences the insulin secretion induced by glucose, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) during a hyperglycaemic clamp in patients with type 2 diabetes (T2DM).', 'A randomized, double-blind, placebo-controlled study was conducted over 12 weeks, during which 25 patients with T2DM completed treatment with either sitagliptin (100\u2009mg once daily) or placebo as add-on therapy to metformin [sitagliptin group (n\u2009=\u200912): mean\u2009±\u2009standard error of the mean (s.e.m.) age 54\u2009±\u20092.5\u2009years, mean\u2009±\u2009s.e.m. HbA1c 7.8\u2009±\u20090.2%; placebo group (n\u2009=\u200913): mean\u2009±\u2009s.e.m. age: 57\u2009±\u20093.0\u2009years, mean\u2009±\u2009s.e.m. HbA1c 7.9\u2009±\u20090.2 %]. In weeks 1 and 12, the patients underwent three 2-h 15-mM hyperglycaemic clamp experiments with infusion of either saline, GLP-1 or GIP. β-cell function was evaluated according to first-phase, second-phase, incremental and total insulin and C-peptide responses.', 'In the sitagliptin group, the mean HbA1c concentration was significantly reduced by 0.9% (p\u2009=\u20090.01). The total β-cell response during GIP infusion improved significantly from week 1 to week 12, both within the sitagliptin group (p\u2009=\u20090.004) and when compared with the placebo group (p\u2009=\u20090.04). The total β-cell response during GLP-1 infusion was significantly higher (p\u2009=\u20090.001) when compared with saline and GIP infusion, but with no improvement from week 1 to week 12. No significant changes in β-cell function occurred in the placebo group.'] Does restoration of the insulinotropic effect of glucose-dependent insulinotropic polypeptide contribute to the antidiabetic effect of dipeptidyl peptidase-4 inhibitors?