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.
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.



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.



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.



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.
Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany.
Oleg
O
Baranov
Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany.|Division of Diabetology, Medical Department I, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany.
Melanie
M
Kahle
Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Carolyn F
CF
Deacon
Department of Biomedical Sciences, Panum Institute, University of Copenhagen, Copenhagen, Denmark.
Jens J
JJ
Holst
Diabeteszentrum Bad Lauterberg, Bad Lauterberg im Harz, Germany. michael.nauck@rub.de.|Division of Diabetology, Medical Department I, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany. michael.nauck@rub.de.
Michael A
MA
Nauck
D000218:Adamantane / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D000368:Aged; D003131:Combined Modality Therapy; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000628:therapy; D003927:Diet, Diabetic; D054873:Dipeptidyl-Peptidase IV Inhibitors; D004311:Double-Blind Method; D015536:Down-Regulation / Q000187:drug effects; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000009:adverse effects; D005081:Exercise Therapy; D025461:Feedback, Physiological / Q000187:drug effects*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D006801:Humans; D008297:Male; D062407:Meals / Q000502:physiology*; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D011759:Pyrrolidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D000068900:Sitagliptin Phosphate / Q000008:administration & dosage* / Q000009:adverse effects; D000077597:Vildagliptin
D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles; D011759:Pyrrolidines; D052216:Glucagon-Like Peptide 1; D008687:Metformin; D000077597:Vildagliptin; D000218:Adamantane; D000068900:Sitagliptin Phosphate

DPP-4 inhibitor; 
GIP
; 
GLP-1; glucose metabolism; sitagliptin; vildagliptin