Cardiovascular and non‐cardiovascular safety of dipeptidyl peptidase‐4 inhibition: a meta‐analysis of randomized controlled cardiovascular outcome trials

Abstract

The full licensing of dipeptidyl peptidase-4 (DPP-4) inhibitors in the USA and Europe requires demonstration of cardiovascular (CV) safety with an upper boundary of harm of 30%. Relative risks (RRs) were: 0.99 [confidence interval (CI) 0.93-1.06] for composite CV-specific death, non-fatal myocardial infarction (MI) and non-fatal stroke; 1.01 (CI 0.91-1.12) for CV-specific death; 0.98 (CI 0.89-1.09) for non-fatal MI; and 1.00 (CI 0.86-1.16) for non-fatal stroke. The risk of acute pancreatitis was increased (RR 1.79; CI 1.13-2.81), equating to 5.5 extra cases/10,000 patients/year (weighted mean) and a number needed to harm of 1940/year. These data provide reassurance about the safety of DPP-4 inhibitors with regard to individual atherothrombotic events and a safety signal for pancreatitis.