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- Title
Effect of ingestion of food on the inhibition of DPPIV activity by oral metformin in type 2 diabetes.
- Authors
Cuthbertson, J.; Patterson, S.; O'Harte, F. P. M.; Bell, P. M.
- Abstract
The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) constitute the enteroinsular axis which promotes postprandial insulin secretion. The therapeutic potential of these hormones in diabetes is limited by their rapid inactivation by the enzyme dipeptidylpeptidase-IV (DPP-IV). Here we investigated the acute effects of metformin in the presence and absence of food on DPP-IV activity in type 2 diabetes Ten subjects with type 2 diabetes (6 male/4 female, age 65.8±15.8 years (mean±SEM), body mass index 30.0±7.5kg/m², HbA1c 6.3±1.2%) received metformin 1g orally or placebo together with a standard mixed meal (SMM) in a random crossover design. Six subjects reattended fasting and received metformin 1g without a SMM. Following SMM (n=10), DPP IV activity was not suppressed by metformin compared with placebo (area under curve AUC0-4h 1574±4 and 1581±8 µmol/min respectively). No differences were observed in plasma glucose, insulin and total GLP-1. After fasting (n=6), DPP IV activity was suppressed (P<0.02) when compared to those given metformin with a SMM (AUC0-4h 1494±9 vs 1578±4 µmol/min). Metformin plasma levels were significantly higher (P<0.03) after fasting than SMM (AUC0-4h 457±55 vs 350±66 mcg/ml). Thus metformin inhibits DPP IV activity in type 2 diabetic patients in the fasting state but not when taken with a standard mixed meal. Metformin plasma concentrations are lower if taken with food. Metformin may have potential for combination therapy with incretin hormones.
- Subjects
GLUCAGON; GLUCOSE; POLYPEPTIDES; METFORMIN; TYPE 2 diabetes; HORMONES
- Publication
Ulster Medical Journal, 2008, Vol 77, Issue 2, p136
- ISSN
0041-6193
- Publication type
Article