Antihyperglycemic agents and cardiovascular outcomes: recent insights.

PURPOSE OF REVIEW: To summarize cardiovascular outcome trials (CVOTs) with antihyperglycemic agents conducted since 2008 US Food and Drug Administration guidance.

RECENT FINDINGS: A 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).

SUMMARY: New-generation CVOTs are shifting the focus in the treatment of T2D to the prevention of cardiovascular morbidity and mortality.