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%. We report a total of 3334 CV events during 86,716 person-years of follow-up in 36,543 patients, when combining data from three trials with formal and prospectively assessed endpoints. Fixed-effect meta-analysis showed that, compared with placebo, DPP-4 inhibition did not increase the upper boundary of risk for the composite endpoint, nor for any individual component by >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.
Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK.
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http://orcid.org/0000-0001-9150-2142
AS
Abbas
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.
H-M
HM
Dehbi
Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK.
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KK
Ray
D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000139:chemically induced*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects*; D004341:Drug Evaluation; D005060:Europe; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000139:chemically induced*; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome; D014481:United States
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007004:Hypoglycemic Agents
DPP-IV inhibitor; antidiabetic drug; cardiovascular disease; meta-analysis