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

TY - JOUR

T1 - The impact of dipeptidyl peptidase 4 inhibition on incretin effect, glucose tolerance, and gastrointestinal-mediated glucose disposal in healthy subjects

AU - Rhee, Nicolai Alexander

AU - Østoft, Signe Harring

AU - Holst, Jens Juul

AU - Deacon, Carolyn

AU - Vilsbøll, Tina

AU - Knop, Filip Krag

PY - 2014/9/1

Y1 - 2014/9/1

N2 - Objective: Inhibition of dipeptidyl peptidase 4 (DPP4) is thought to intensify the physiological effects of the incretin hormones. We investigated the effects of DPP4 inhibition on plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP1), incretin effect, glucose tolerance, gastrointestinal-mediated glucose disposal (GIGD) and gastric emptying in healthy subjects.Design: A randomised, controlled and open-labelled study.Methods: Ten healthy subjects (six women; age, 40±5 years (mean±S.E.M.); BMI, 24±3 kg/m; fasting plasma glucose, 5.1±0.2 mmol/l and HbA1c, 34±1 mmol/mol (5.3±0.1%)) were randomised to two-paired study days comprising a 4-h 50g oral glucose tolerance test (OGTT) with paracetamol (A) and an isoglycaemic intravenous (i.v.) glucose infusion (B), with (A1CB1) and without (A2CB2) preceding administration of the DPP4 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 GLP1 and GIP were seen after DPP4 inhibition. No significant impact of DPP4 inhibition on fasting plasma glucose (5.1±0.1 vs 4.9±0.1 mmol/l, P=0.3), glucose tolerance (area under the curve (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 DPP4 inhibitor) vs 40±7% (with DPP4 inhibitor), P=1.0), glucagons responses (1395±165 vs 1223±195 pmol/l×min, P=0.41), GIGD (52±4 vs 56G5%, P=0.40) nor gastric emptying (Tmax for plasma paracetamol: 86±9 vs 80±12 min, P=0.60) changed following DPP4 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.

AB - Objective: Inhibition of dipeptidyl peptidase 4 (DPP4) is thought to intensify the physiological effects of the incretin hormones. We investigated the effects of DPP4 inhibition on plasma levels of glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP1), incretin effect, glucose tolerance, gastrointestinal-mediated glucose disposal (GIGD) and gastric emptying in healthy subjects.Design: A randomised, controlled and open-labelled study.Methods: Ten healthy subjects (six women; age, 40±5 years (mean±S.E.M.); BMI, 24±3 kg/m; fasting plasma glucose, 5.1±0.2 mmol/l and HbA1c, 34±1 mmol/mol (5.3±0.1%)) were randomised to two-paired study days comprising a 4-h 50g oral glucose tolerance test (OGTT) with paracetamol (A) and an isoglycaemic intravenous (i.v.) glucose infusion (B), with (A1CB1) and without (A2CB2) preceding administration of the DPP4 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 GLP1 and GIP were seen after DPP4 inhibition. No significant impact of DPP4 inhibition on fasting plasma glucose (5.1±0.1 vs 4.9±0.1 mmol/l, P=0.3), glucose tolerance (area under the curve (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 DPP4 inhibitor) vs 40±7% (with DPP4 inhibitor), P=1.0), glucagons responses (1395±165 vs 1223±195 pmol/l×min, P=0.41), GIGD (52±4 vs 56G5%, P=0.40) nor gastric emptying (Tmax for plasma paracetamol: 86±9 vs 80±12 min, P=0.60) changed following DPP4 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.

U2 - 10.1530/EJE-14-0314

DO - 10.1530/EJE-14-0314

M3 - Journal article

C2 - 24935932

SN - 0804-4643

VL - 171

SP - 353

EP - 362

JO - European Journal of Endocrinology

JF - European Journal of Endocrinology

IS - 3

ER -