Aims
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).
Methods
A randomized, double‐blind, placebo‐controlled study was conducted over 12 weeks, during which 25 patients with T2DM completed treatment with either sitagliptin (100 mg once daily) or placebo as add‐on therapy to metformin [sitagliptin group (n = 12): mean ± standard error of the mean (s.e.m.) age 54 ± 2.5 years, mean ± s.e.m. HbA1c 7.8 ± 0.2%; placebo group (n = 13): mean ± s.e.m. age: 57 ± 3.0 years, mean ± s.e.m. HbA1c 7.9 ± 0.2 %]. 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.
Results
In the sitagliptin group, the mean HbA1c concentration was significantly reduced by 0.9% (p = 0.01). The total β‐cell response during GIP infusion improved signficantly from week 1 to week 12, both within the sitagliptin group (p = 0.004) and when compared with the placebo group (p = 0.04). The total β‐cell response during GLP‐1 infusion was significantly higher (p = 0.001) 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.
Conclusions
Treatment with the DPP‐4 inhibitor sitagliptin over 12 weeks in patients with T2DM partially restored the lost insulinotropic effect of GIP, whereas the preserved insulinotropic effect of GLP‐1 was not further improved. A gradual enhancement of the insulinotropic effect of GIP, therefore, possibly contributes to the antidiabetic actions of DPP‐4 inhibitors.