A Protein Preload Enhances the Glucose-Lowering Efficacy of Vildagliptin in Type 2 Diabetes

Diabetes Care. 2016 Apr;39(4):511-7. doi: 10.2337/dc15-2298. Epub 2016 Jan 19.

Abstract

Objective: Nutrient "preloads" given before meals can attenuate postprandial glycemic excursions, at least partly by slowing gastric emptying and stimulating secretion of the incretins (i.e., glucagon-like peptide-1 [GLP-1] and glucose-dependent insulinotropic polypeptide [GIP]). This study was designed to evaluate whether a protein preload could improve the efficacy of the dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin to increase incretin concentrations, slow gastric emptying, and lower postprandial glycemia in type 2 diabetes.

Research design and methods: Twenty-two patients with type 2 diabetes treated with metformin were studied on four occasions, receiving either 50 mg vildagliptin (VILD) or placebo (PLBO) on both the evening before and the morning of each study day. The latter dose was followed after 60 min by a preload drink containing either 25 g whey protein (WHEY) or control flavoring (CTRL), and after another 30 min by a (13)C-octanoate-labeled mashed potato meal. Plasma glucose and hormones, and gastric emptying, were evaluated.

Results: Compared with PLBO/CTRL, PLBO/WHEY reduced postprandial peak glycemia, increased plasma insulin, glucagon, and incretin hormones (total and intact), and slowed gastric emptying, whereas VILD/CTRL reduced both the peak and area under the curve for glucose, increased plasma intact incretins, and slowed gastric emptying but suppressed plasma glucagon and total incretins (P < 0.05 each). Compared with both PLBO/WHEY and VILD/CTRL, VILD/WHEY was associated with higher plasma intact GLP-1 and GIP, slower gastric emptying, and lower postprandial glycemia (P < 0.05 each).

Conclusions: In metformin-treated type 2 diabetes, a protein preload has the capacity to enhance the efficacy of vildagliptin to slow gastric emptying, increase plasma intact incretins, and reduce postprandial glycemia.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adamantane / analogs & derivatives*
  • Adamantane / therapeutic use
  • Aged
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Double-Blind Method
  • Gastric Emptying / drug effects
  • Gastric Inhibitory Polypeptide / blood
  • Glucagon / blood
  • Glucagon-Like Peptide 1 / blood
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Incretins / therapeutic use
  • Insulin / blood
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Nitriles / therapeutic use*
  • Postprandial Period / drug effects
  • Pyrrolidines / therapeutic use*
  • Vildagliptin
  • Whey Proteins / administration & dosage*

Substances

  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Incretins
  • Insulin
  • Nitriles
  • Pyrrolidines
  • Whey Proteins
  • Gastric Inhibitory Polypeptide
  • Glucagon-Like Peptide 1
  • Glucagon
  • Metformin
  • Vildagliptin
  • Adamantane