Dipeptidyl peptidase (DPP-IV) rapidly metabolises hormones such as glucagon-like peptide-1(7-36)amide. This study evaluated circulating DPP-IV activity in type 2 diabetic patients in relation to GLP-1 degradation and metabolic control. Blood samples were collected from type 2 diabetic patients in three main categories: good glycaemic control (HbA(1c) 9%). Age- and sex-matched non-diabetic subjects were used as controls. Circulating DPP-IV activity of healthy control subjects was 22.5 +/- 0.7 nmol/ml/min (n = 70). In the combined groups of type 2 diabetic subjects, circulating DPP-IV activity was significantly decreased at 18.1 +/- 0.7 nmol/ml/min (p <0.001, n = 54). DPP-IV activity was negatively correlated with both glucose (p <0.01) and HbA(1c) (p <0.01) in this population. Furthermore, DPP-IV activity was reduced 1.2-fold (p <0.01, n = 25), 1.3-fold (p <0.001, n = 19) and 1.3-fold (p <0.05, n =10) in good, moderate and poorly controlled diabetic groups, 18.7 +/- 1.0, 17.4 +/- 1.4 and 18.0 +/- 1.5 nmol/ml/min, respectively. Degradation of GLP-1 by in vitro incubation with pooled plasma samples from healthy and type 2 diabetic subjects revealed decreased degradation to the inactive metabolite, GLP-1(9-36), in the diabetic group. These data indicate decreased DPP-IV activity and GLP-1 degradation in type 2 diabetes. DPP-IV enzyme activity appears to be depressed in response to poor glycaemic control. (c). 2007 Elsevier Ireland Ltd. All rights reserved.