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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
Author(s) -
Baranov Oleg,
Kahle Melanie,
Deacon Carolyn F.,
Holst Jens J.,
Nauck Michael A.
Publication year - 2016
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.12706
Subject(s) - vildagliptin , sitagliptin , incretin , medicine , metformin , endocrinology , glucagon like peptide 1 , gastric inhibitory polypeptide , glucagon , dipeptidyl peptidase 4 , sitagliptin phosphate , type 2 diabetes , insulin , hormone , dipeptidyl peptidase , diabetes mellitus , chemistry , biochemistry , enzyme
Aim To compare directly the clinical effects of vildagliptin and sitagliptin in patients with type 2 diabetes, with a special emphasis on incretin hormones and L ‐cell feedback inhibition induced by dipeptidyl peptidase ( DPP ‐4) inhibition. Methods A total of 24 patients (12 on a diet/exercise regimen, 12 on metformin) were treated, in randomized order, for 7‐9 days, with either vildagliptin (50 mg twice daily = 100 mg/d), sitagliptin (100 mg once daily in those on diet, 50 mg twice daily in those on metformin treatment = 100 mg/d) or placebo (twice daily). A mixed‐meal test was performed. Results Intact glucagon‐like peptide‐1 ( GLP ‐1) and glucose‐dependent insulinotropic polypeptide concentrations were doubled by both DPP ‐4 inhibitors. Meal‐related total GLP ‐1 responses were reduced by vildagliptin and sitagliptin treatment alike in the majority of patients (vildagliptin: p = 0.0005; sitagliptin: p = 0.019), but with substantial inter‐individual variation. L ‐cell feedback appeared to be more pronounced in those whose intact GLP ‐1 relative to total GLP ‐1 increased more, and who had greater reductions in fasting plasma glucose after DPP ‐4 inhibition. K ‐cell feedback inhibition overall was not significant. There were no differences in any of the clinical variables (glycaemia, insulin and glucagon secretory responses) between vildagliptin and sitagliptin treatment. Conclusions 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.