Investigation of the effect of oral metformin on dipeptidylpeptidase-4 (DPP-4) activity in Type 2 diabetes

J Cuthbertson, S Patterson, FPM O'Harte, PM Bell

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Abstract

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. Ten subjects with Type 2 diabetes (6 male/4 female, age 65.8 +/- 2.6 years, body mass index 30.0 +/- 1.2 kg/m(2), 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. 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 mu mol/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 mu mol/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). 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.
LanguageEnglish
Pages649-654
JournalDiabetic medicine
Volume26
Issue number6
DOIs
Publication statusPublished - Jun 2009

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Metformin
Type 2 Diabetes Mellitus
Meals
Fasting
Area Under Curve
Glucagon-Like Peptide 1
Placebos
Food
Glycosylated Hemoglobin A
Serum
Pharmaceutical Preparations
Cross-Over Studies
Body Mass Index
Hormones
Insulin
Glucose
Enzymes

Cite this

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title = "Investigation of the effect of oral metformin on dipeptidylpeptidase-4 (DPP-4) activity in Type 2 diabetes",
abstract = "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. Ten subjects with Type 2 diabetes (6 male/4 female, age 65.8 +/- 2.6 years, body mass index 30.0 +/- 1.2 kg/m(2), 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. 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 mu mol/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 mu mol/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). 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.",
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Investigation of the effect of oral metformin on dipeptidylpeptidase-4 (DPP-4) activity in Type 2 diabetes. / Cuthbertson, J; Patterson, S; O'Harte, FPM; Bell, PM.

In: Diabetic medicine, Vol. 26, No. 6, 06.2009, p. 649-654.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Investigation of the effect of oral metformin on dipeptidylpeptidase-4 (DPP-4) activity in Type 2 diabetes

AU - Cuthbertson, J

AU - Patterson, S

AU - O'Harte, FPM

AU - Bell, PM

PY - 2009/6

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N2 - 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. Ten subjects with Type 2 diabetes (6 male/4 female, age 65.8 +/- 2.6 years, body mass index 30.0 +/- 1.2 kg/m(2), 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. 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 mu mol/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 mu mol/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). 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.

AB - 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. Ten subjects with Type 2 diabetes (6 male/4 female, age 65.8 +/- 2.6 years, body mass index 30.0 +/- 1.2 kg/m(2), 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. 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 mu mol/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 mu mol/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). 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.

U2 - 10.1111/j.1464-5491.2009.02748.x

DO - 10.1111/j.1464-5491.2009.02748.x

M3 - Article

VL - 26

SP - 649

EP - 654

JO - Diabetes Medicine

T2 - Diabetes Medicine

JF - Diabetes Medicine

SN - 0742-3071

IS - 6

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