AIMS: Glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone and major component of the enteroinsular axis. Its therapeutic potential in human diabetes is limited by rapid degradation and inactivation by the enzyme dipeptidylpeptidase-4 (DPP-4). We investigated the acute effects of metformin with and without food on DPP-4 activity in Type 2 diabetes. METHODS:Ten subjects with Type 2 diabetes (6 male/4 female, age 65.8 +/- 2.6 years, body mass index 30.0 +/- 1.2 kg/m2, glycated haemoglobin (HbA(1c)) 6.3 +/- 0.2%, mean +/- SEM) received metformin 1 g orally or placebo together with a standard mixed meal (SMM) in a random crossover design. Six subjects re-attended fasting and receivedmetformin 1 g without a SMM. RESULTS: Following SMM (n = 10), DPP-4 activity was not suppressed by metformin compared with placebo [area under curve (AUC)(0-4 h) 1574 +/- 4 vs. 1581 +/- 8 micromol/ml/min, respectively]. Plasma glucose, insulin and active GLP-1 were not different. However, DPP-4 activity was suppressed with metformin following fasting compared with a SMM (n = 6) (AUC(0-4 h) 1578 +/- 4 vs. 1494 +/- 9 micromol/min, P < 0.02). Metformin serum levels were significantly lower (P < 0.001) after SMM than fasting (AUC(0-4 h) 350 +/- 66vs. 457 +/- 55 mg/ml/min). CONCLUSION:Metformin inhibits DPP-4 activity in Type 2 diabetic patients in the fasting state but not when taken with a standard mixed meal. Metformin serum concentrations are lower if the drug is taken with food. These findings should be taken into account in establishing how to maximize efficacy of the drug.
RCT Entities:
AIMS: Glucagon-like peptide-1 (GLP-1) is an insulinotropic hormone and major component of the enteroinsular axis. Its therapeutic potential in humandiabetes is limited by rapid degradation and inactivation by the enzyme dipeptidylpeptidase-4 (DPP-4). We investigated the acute effects of metformin with and without food on DPP-4 activity in Type 2 diabetes. METHODS: Ten subjects with Type 2 diabetes (6 male/4 female, age 65.8 +/- 2.6 years, body mass index 30.0 +/- 1.2 kg/m2, glycated haemoglobin (HbA(1c)) 6.3 +/- 0.2%, mean +/- SEM) received metformin 1 g orally or placebo together with a standard mixed meal (SMM) in a random crossover design. Six subjects re-attended fasting and received metformin 1 g without a SMM. RESULTS: Following SMM (n = 10), DPP-4 activity was not suppressed by metformin compared with placebo [area under curve (AUC)(0-4 h) 1574 +/- 4 vs. 1581 +/- 8 micromol/ml/min, respectively]. Plasma glucose, insulin and active GLP-1 were not different. However, DPP-4 activity was suppressed with metformin following fasting compared with a SMM (n = 6) (AUC(0-4 h) 1578 +/- 4 vs. 1494 +/- 9 micromol/min, P < 0.02). Metformin serum levels were significantly lower (P < 0.001) after SMM than fasting (AUC(0-4 h) 350 +/- 66 vs. 457 +/- 55 mg/ml/min). CONCLUSION:Metformin inhibits DPP-4 activity in Type 2 diabeticpatients in the fasting state but not when taken with a standard mixed meal. Metformin serum concentrations are lower if the drug is taken with food. These findings should be taken into account in establishing how to maximize efficacy of the drug.
Authors: Chris P H Lexis; Iwan C C van der Horst; Erik Lipsic; Pim van der Harst; Anouk N A van der Horst-Schrivers; Bruce H R Wolffenbuttel; Rudolf A de Boer; Albert C van Rossum; Dirk J van Veldhuisen; Bart J G L de Smet Journal: Cardiovasc Drugs Ther Date: 2012-10 Impact factor: 3.727
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Authors: Jong Ho Kim; Sang Soo Kim; Hong Sun Baek; In Kyu Lee; Dong Jin Chung; Ho Sang Sohn; Hak Yeon Bae; Mi Kyung Kim; Jeong Hyun Park; Young Sik Choi; Young Il Kim; Jong Ryeal Hahm; Chang Won Lee; Sung Rae Jo; Mi Kyung Park; Kwang Jae Lee; In Joo Kim Journal: Diabetes Metab J Date: 2016-04-21 Impact factor: 5.376