Glycemic effects and safety of L-Glutamine supplementation with or without sitagliptin in type 2 diabetes patients-a randomized study

Dorit Samocha-Bonet, Donald J Chisholm, Fiona M Gribble, Adelle C F Coster, Kevin H Carpenter, Graham R D Jones, Jens J Holst, Jerry R Greenfield, Dorit Samocha-Bonet, Donald J Chisholm, Fiona M Gribble, Adelle C F Coster, Kevin H Carpenter, Graham R D Jones, Jens J Holst, Jerry R Greenfield

Abstract

Background and aims: L-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.

Methods: Type 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.

Results: HbA1c (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).

Conclusions: Daily 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 registration: ClincalTrials.gov NCT00673894.

Conflict of interest statement

Competing Interests: Carpenter KH, Coster ACF, and Jones GRD have nothing to declare; Chisholm DJ has been a board member for Astra Zeneca/Bristol Myer Squibb (Member/Chairman of Australian and International Advisory Board) and has received speaker honoraria from Astra Zeneca/Bristol Myers Squibb and MSD; Gribble FM is a board member of BioKier, consultant for Roche, and has received speaker honoraria from Novo Nordisk and Merck, and travel/accommodation expenses from Merck. Holst JJ is a consultant to NovoNordisk and holds grants from Novartis and Merck. Greenfield JR was a Principal Investigator on an Investigator-Initiated Studies Program grant from Merck and Co., awarded to the Garvan Institute of Medical Research, and Samocha-Bonet D was partly supported by this grant. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Figure 1. Flow of participants in the…
Figure 1. Flow of participants in the study.
*Other reasons include participant not able to take time off work or other engagements (n = 3), family not approving (n = 2), underlying disease (n = 3), weight unstable or actively trying to lose weight (n = 2), change of mind (n = 1) and inability to provide informed consent (n = 1).
Figure 2. Study timeline.
Figure 2. Study timeline.
The effect of glutamine with sitagliptin or placebo was assessed in a randomized crossover study. Each study period (A and B) was initiated with 2-weeks lead-in followed by L-glutamine (Gln) 15 g with breakfast and dinner with either sitagliptin (Sit; 100 mg) or placebo for 4 weeks. Participants visited the Clinical Research Facility at day 0 (Baseline) and 4-weeks of studies A and B for a meal challenge. Treatments were randomly assigned with a 4–6 week washout period between A and B studies.
Figure 3. The effect of glutamine +…
Figure 3. The effect of glutamine + sitagliptin and glutamine + placebo on postprandial circulating concentrations of glucose, insulin and glucagon-like peptide-1.
Postprandial circulating concentrations of blood glucose (A), serum insulin (B), insulin to glucose ratio (C) and plasma total and active GLP-1 (D and E, respectively) at baseline (day 0; empty symbols) and 4-weeks (dark symbols) of glutamine + sitagliptin (Gln + Sit; squares) and glutamine + placebo (Gln + Placebo; circles) in type 2 diabetes patients (n = 13). Data are means ± SEM. Significance of the repeated measure ANOVA with time (within subjects factor, **P<0.01) and the interaction of time with treatments (the between subjects factor, ##P≤0.01) in the AUC is given (n = 13).

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