Antihyperglycemic agents and cardiovascular outcomes: recent insights

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Purpose of reviewTo summarize cardiovascular outcome trials (CVOTs) with antihyperglycemic agents conducted since 2008 US Food and Drug Administration guidance.Recent findingsA series of large CVOTs since 2008 have included patients with type 2 diabetes (T2D), who are otherwise treated according to standard of care. After the initial trials with incretin agents demonstrated cardiovascular safety, two recent CVOTs with currently available antihyperglycemic agents – EMPA-REG OUTCOME with empagliflozin and LEADER with liraglutide – show a significant reduction of the primary composite outcome, including a significant difference in the cardiovascular death end-point in both trials [EMPA-REG OUTCOME: hazard ratio = 0.62, confidence interval (CI) = 0.49–0.77, P < 0.001 and LEADER: hazard ratio = 0.78, CI = 0.66–0.93, P = 0.007]. Number needed to treat to prevent one cardiovascular death of 46 and 77 for empagliflozin and liraglutide, respectively, over 3 years is comparable with other currently employed evidence-based cardioprotective strategies. In addition, EMPA-REG OUTCOME trial had a robust reduction in hospitalization for heart failure (hazard ratio = 0.65, CI = 0.50–0.85, P = 0.002).SummaryNew-generation CVOTs are shifting the focus in the treatment of T2D to the prevention of cardiovascular morbidity and mortality.

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