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

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Cuthbertson, J, Patterson, S, O'Harte, FPM and Bell, PM (2009) Investigation of the effect of oral metformin on dipeptidylpeptidase-4 (DPP-4) activity in Type 2 diabetes. DIABETIC MEDICINE, 26 (6). pp. 649-654. [Journal article]

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DOI: 10.1111/j.1464-5491.2009.02748.x

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.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:6436
Deposited By:Professor Finbarr O'Harte
Deposited On:11 Jan 2010 10:35
Last Modified:27 Jun 2011 14:55

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