The impact of dipeptidyl peptidase 4 inhibition on incretin effect, glucose tolerance, and gastrointestinal-mediated glucose disposal in healthy subjects

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Nicolai Alexander Rhee, Signe Harring Østoft, Jens Juul Holst, Carolyn Deacon, Tina Vilsbøll, Filip Krag Knop

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.

Original languageEnglish
JournalEuropean Journal of Endocrinology
Volume171
Issue number3
Pages (from-to)353-362
Number of pages10
ISSN0804-4643
DOIs
Publication statusPublished - 16 Jun 2014

ID: 117850771