On Combination Therapy of Diabetes With Metformin and Dipeptidyl Peptidase IV Inhibitors

Recently, data were presented showing that metformin increased plasma active glucagon-like peptide (GLP)-1[7–36NH2] concentrations in obese nondiabetic male patients (1), and it was suggested that metformin was a direct dipeptidyl peptidase (DP) IV inhibitor. Contradiction of this hypothesis is simply found by examining the modes of action of metformin and of the DP IV inhibitors. Although the specific molecular target of metformin is still unknown, biguanides generally act to sensitize peripheral tissues to insulin action (particularly, skeletal muscle) and inhibit hepatic gluconeogenesis and glycogenolysis (2,3,4). In contrast, DP IV inhibitors act to enhance the insulin response to a meal, via preservation of …