The impact of dipeptidyl peptidase 4 inhibition on incretin effect, glucose tolerance, and gastrointestinal-mediated glucose disposal in healthy subjects
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Objective Inhibition of dipeptidyl peptidase 4 (DPP-4), is thought to intensify the physiological effects of the incretin hormones. We investigated the effects of DPP-4 inhibition on plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), the incretin effect, glucose tolerance, gastrointestinal-mediated glucose disposal (GIGD) and gastric emptying in healthy subjects. Design Randomised, controlled, open-label. Methods Ten healthy subjects (6 women) (age: 40±5 years (mean±SEM); BMI: 24±3 kg/m2, fasting plasma glucose: 5.1±0.2 mmol/l; HbA1c: 34±1 mmol/mol [5.3±0.1%]) were randomised to two paired study days comprising a 4h 50 g-OGTT with paracetamol (A) and an isoglycaemic i.v. glucose infusion (IIGI) (B), with (A1+B1) and without (A2+B2) preceding administration of the DPP-4 inhibitor sitagliptin. Results Isoglycaemia was obtained in all subjects on the paired study days. Significant increases in fasting levels and OGTT-induced responses of active GLP-1 and GIP were seen after DPP-4 inhibition. No significant impact of DPP-4 inhibition on fasting plasma glucose (5.1±0.1 vs 4.9±0.1 mmol/l, p=0.3), glucose tolerance (AUC for plasma glucose: 151±35 vs 137±26 mmol/l×min, p=0.7) or peak plasma glucose during OGTT (8.5±0.4 vs 8.1±0.3 mmol/l, p=0.3) was observed. Neither incretin effect (40±9 (without DPP-4 inhibitor) vs 40±7% (with DPP-4 inhibitor), p=1.0), glucagon responses (1,395±165 vs 1,223±195 pmol/l×min, p=0.41), GIGD (52±4 vs 56±5%, p=0.40) nor gastric emptying (Tmax for plasma paracetamol: 86±9 vs 80±12 min, p=0.60) changed following DPP-4 inhibition. Conclusions These results suggest that acute increases in active incretin hormone levels do not affect glucose tolerance, GIGD, incretin effect, glucagon responses or gastric emptying in healthy subjects.
|Journal||European Journal of Endocrinology|
|Number of pages||10|
|Publication status||Published - 16 Jun 2014|