Endocrine Abstracts

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±S.E.M.), body mass index 30.0±7.5 kg/m², HbA1c 6.3±1.2%) received metformin 1 g orally or placebo together with a standard mixed meal (SMM) in a random crossover design. Six subjects reattended fasting and received metformin 1 g without a SMM.

Following SMM (n=10), DPP IV activity was not suppressed by metformin compared with placebo (area under curve AUC _0-4h 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 (AUC _0-4h 1494±9 vs 1578±4 μmol/min). Metformin plasma levels were significantly higher (P<0.03) after fasting than SMM (AUC _0-4h 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.