Feedback suppression of meal‐induced glucagon‐like peptide‐1 (GLP‐1) secretion mediated through elevations in intact GLP‐1 caused by dipeptidyl peptidase‐4 inhibition: a randomized, prospective comparison of sitagliptin and vildagliptin treatment

Abstract

Vildagliptin and sitagliptin affected incretin hormones, glucose concentrations, insulin and glucagon secretion in a similar manner. Inter-individual variations in L-cell feedback inhibition may indicate heterogeneity in the clinical response to DPP-4 inhibition.

Addition of a dipeptidyl peptidase‐4 inhibitor, sitagliptin, to ongoing therapy with the glucagon‐like peptide‐1 receptor agonist liraglutide: A randomized controlled trial in patients with type 2 diabetes

“…A recent study from our group studying similar patients on metformin and using a similar meal challenge found intact and total GLP‐1 and GIP concentrations very similar to those observed in the present study (Table S4, Appendix S1) . Nevertheless, in the absence of a GLP‐1 receptor agonist, sitagliptin induced a more obvious reduction in plasma glucose than observed in the present study, i.e. on a background of metformin and liraglutide.…”

“…Previous studies of sufficient sample size have clearly shown reductions in post‐meal glycaemic excursions with DPP‐4 inhibitor treatment in participants not receiving treatment with a GLP‐1 receptor agonist . A recent study from our group studying similar patients on metformin and using a similar meal challenge found intact and total GLP‐1 and GIP concentrations very similar to those observed in the present study (Table S4, Appendix S1) . Nevertheless, in the absence of a GLP‐1 receptor agonist, sitagliptin induced a more obvious reduction in plasma glucose than observed in the present study, i.e.…”

Persistent whole day meal effects of three dipeptidyl peptidase‐4 inhibitors on glycaemia and hormonal responses in metformin‐treated type 2 diabetes

“…This is probably a feedback inhibition by the incretin hormone of their own secretion from K‐ and L‐cells. This has previously been suggested for GIP and GLP‐1 . The current study shows this feedback inhibition after each meal during a whole day.…”

Effects on the glucagon response to hypoglycaemia during DPP‐4 inhibition in elderly subjects with type 2 diabetes: A randomized, placebo‐controlled study

“…This confirms a previous report on the effect of sitagliptin on total GIP levels after meal ingestion in healthy subjects and in patients with type 2 diabetes . Also, 2 other studies have shown a trend for a feedback inhibition by DPP‐4 inhibition on GIP secretion in type 2 diabetes, although of lesser magnitude than feedback inhibition of GLP‐1 secretion . These results are at variance with another previous study and further studies are warranted.…”

“…This measurement involves both the intact and degraded products of the hormones, and therefore reflects the total secretion of the hormones . The secretion of GLP‐1 has been demonstrated previously to be reduced by DPP‐4 inhibition, which is explained by a feedback inhibition by intact GLP‐1 on GLP‐1 secretion . We confirm this feedback in the present study as the concentrations of total GLP‐1 were lower after sitagliptin than after placebo during the clamp procedure and after the lunch meal, with a trend also after the breakfast meal.…”