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

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.

• Authors: Oleg Baranov, Melanie Kahle, Carolyn F Deacon, Jens J Holst, Michael A Nauck
• Journal: Diabetes, obesity & metabolism (Diabetes Obes Metab) Vol. 18 Issue 11 Pg. 1100-1109 (11 2016) ISSN: 1463-1326 [Electronic] England
• PMID: 27300579 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial)
• Copyright: © 2016 John Wiley & Sons Ltd.

Chemical References

• Dipeptidyl-Peptidase IV Inhibitors
• Nitriles
• Pyrrolidines
• Glucagon-Like Peptide 1
• Metformin
• Vildagliptin
• Adamantane
• Sitagliptin Phosphate

Topics

• Adamantane (administration & dosage, adverse effects, analogs & derivatives, pharmacology)
• Aged
• Combined Modality Therapy
• Cross-Over Studies
• Diabetes Mellitus, Type 2 (drug therapy, metabolism, therapy)
• Diet, Diabetic
• Dipeptidyl-Peptidase IV Inhibitors
• Double-Blind Method
• Down-Regulation (drug effects)
• Drug Administration Schedule
• Drug Therapy, Combination (adverse effects)
• Exercise Therapy
• Feedback, Physiological (drug effects)
• Female
• Glucagon-Like Peptide 1 (metabolism)
• Humans
• Male
• Meals (physiology)
• Metformin (administration & dosage, adverse effects)
• Middle Aged
• Nitriles (administration & dosage, adverse effects, pharmacology)
• Pyrrolidines (administration & dosage, adverse effects, pharmacology)
• Sitagliptin Phosphate (administration & dosage, adverse effects)
• Vildagliptin