Abstract

Background and AimsL-glutamine is an efficacious glucagon-like peptide (GLP)-1 secretagogue in vitro. When administered with a meal, glutamine increases GLP-1 and insulin excursions and reduces postprandial glycaemia in type 2 diabetes patients. The aim of the study was to assess the efficacy and safety of daily glutamine supplementation with or without the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin in well-controlled type 2 diabetes patients.MethodsType 2 diabetes patients treated with metformin (n = 13, 9 men) with baseline glycated hemoglobin (HbA1c) 7.1±0.3% (54±4 mmol/mol) received glutamine (15 g bd)+ sitagliptin (100 mg/d) or glutamine (15 g bd) + placebo for 4 weeks in a randomized crossover study.ResultsHbA1c (P = 0.007) and fructosamine (P = 0.02) decreased modestly, without significant time-treatment interactions (both P = 0.4). Blood urea increased (P<0.001) without a significant time-treatment interaction (P = 0.8), but creatinine and estimated glomerular filtration rate (eGFR) were unchanged (P≥0.5). Red blood cells, hemoglobin, hematocrit, and albumin modestly decreased (P≤0.02), without significant time-treatment interactions (P≥0.4). Body weight and plasma electrolytes remained unchanged (P≥0.2).ConclusionsDaily oral supplementation of glutamine with or without sitagliptin for 4 weeks decreased glycaemia in well-controlled type 2 diabetes patients, but was also associated with mild plasma volume expansion.Trial RegistrationClincalTrials.gov NCT00673894

Highlights

  • Impaired insulin secretion contributes to hyperglycemia in type 2 diabetes

  • Enhancement of glucagon-like peptide (GLP)-1 secretion with meals has the advantage of increasing GLP-1 concentrations in the intestinal milieu, where it is believed to act on vagal neurons and mediate its central effects

  • Fasting active GLP-1 increased with both treatments (0.460.6 and 1.061.2 pmol/L with glutamine + placebo and 0.861.0 and 2.361.6 pmol/L with glutamine + sitagliptin at baseline and 4 weeks, respectively, P#0.001), without a significant time-treatment interaction (P = 0.1)

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Summary

Introduction

Impaired insulin secretion contributes to hyperglycemia in type 2 diabetes. Glucagon-like peptide (GLP)-1 is secreted from intestinal L-cells in response to nutrients and is rapidly degraded by dipeptidyl peptidase (DPP)-4. GLP-1 contributes to myriad of metabolic effects, including insulin secretion, beta cell proliferation, slowing of gastric emptying and increased satiety; all are desirable features of type 2 diabetes therapy [1,2,3]. GLP-1 receptor agonists and DPP-4 inhibitors are used to treat type 2 diabetes patients. When administered with a meal, glutamine increases GLP-1 and insulin excursions and reduces postprandial glycaemia in type 2 diabetes patients. The aim of the study was to assess the efficacy and safety of daily glutamine supplementation with or without the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin in well-controlled type 2 diabetes patients

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