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

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.