The role of dipeptidyl peptidase-4 inhibitors

Type 2 diabetes is a progressive disease and greater treatment intensity is needed over time to control increasingly abnormal glucose concentrations.1 In the linked article (doi:10.1136/bmj.e1369), Karagiannis and colleagues present a systematic review and meta-analysis of the risks and benefits associated with one of the relatively new classes of oral hypoglycaemic drugs, the dipeptidyl peptidase-4 (DPP-4) inhibitors.2

DPP-4 inhibitors reduce the breakdown of the glucose responsive incretin hormones, mainly glucagon-like peptide 1 (GLP-1); they have multiple physiological effects that together normalise glucose homeostasis without increasing body weight.3 Because GLP-1 is released in response to raised rather than normal glucose concentrations, DPP-4 inhibitors may be less likely to cause hypoglycaemia than other oral hypoglycaemic agents.3 Increased GLP-1 activity is associated with favourable changes in cardiovascular risk parameters of weight, lipids, blood pressure, and ventricular function, but no trials of DPP-4 inhibitors that are powered to detect differences in cardiovascular events have been reported.4

Karagiannis and colleagues examined two potential roles of DPP-4 inhibitors in type 2 diabetes: as monotherapy (compared with metformin) and …