Abstract
Introduction: The association between glucose-lowering in subjects with diabetes mellitus and major cardiovascular (CV) outcomes is weak. Furthermore, some oral hypoglycaemic agents are associated with increased CV events. Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) are a new class of oral hypoglycemic agent that may have beneficial CV effects. Objectives: We undertook a systematic review to appraise the CV safety and efficacy of DPP-4 inhibitors. Methods: A comprehensive search for published and unpublished prospective trials comparing DPP4i with placebo and active comparators was performed. Trials were eligible for inclusion if they reported on at least one of the outcomes examined, recruited minimum 100 patients and follow-up was a minimum of 24 weeks. We performed a meta-analysis of the relative risk (RR) using the Mantel-Haenszel random effects model for mortality and major cardiovascular (CV) outcomes. Results: 50 trials met inclusion criteria, enrolling 55,232 patients with a mean follow-up of 42.8 weeks. When DPP4i were compared to all comparators (placebo and active), there was no difference in all-cause mortality (n1⁄451,073, RR 1.01, 95% CI 0.91-1.13, p1⁄40.81), CV mortality (n1⁄448,242 RR 0.98, 95% CI 0.85-1.12, p1⁄40.70, acute coronary syndrome (n1⁄453,125 RR 0.97, 95% CI 0.87-1.08, p1⁄40.61) or stroke (n1⁄442,737, RR 0.98, 95% CI 0.81-1.18, p1⁄40.80). There was statistically significant increase in heart failure outcomes (clinically significant HF and hospitalisations) (n1⁄434,573, RR 1.19, 95% CI 1.01-1.39, p1⁄40.03), also seen when DPP-4 inhibitors were compared to placebo (RR 1.20, 95% CI 1.02-1.40, p1⁄40.03). Conclusion: Treatment with DPP-4 inhibitors compared with placebo shows a nominally statistically significant trend towards increased risk of HF outcomes. Against active comparator, DPP-4 inhibitors demonstrated a reduction in ACS and stroke. It will be important to see if these findings are also observed in other large-scale CV outcome studies with these agents. Disclosure of Interest: None Declared
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