Hypoglycemia, Cardiovascular Outcomes, and Death: The LEADER Experience

OBJECTIVE: In the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) cardiovascular (CV) outcomes trial (NCT01179048), liraglutide significantly reduced the risk of CV events (by 13%) and hypoglycemia versus placebo. This post hoc analysis examines the associations between hypoglycemia and CV outcomes and death. RESEARCH DESIGN AND METHODS: = 9,340) were randomized 1:1 to liraglutide or placebo, both in addition to standard treatment, and followed for 3.5-5 years. The primary end point was time to first major adverse cardiovascular event (MACE) (1,302 first events recorded), and secondary end points included incidence of hypoglycemia. We used Cox regression to analyze time to first MACE, CV death, non-CV death, or all-cause death with hypoglycemia as a factor or time-dependent covariate. RESULTS: -interaction = 0.90). CONCLUSIONS: Patients experiencing severe hypoglycemia were at greater risk of CV events and death, particularly shortly after the hypoglycemic episode. While causality remains unclear, reducing hypoglycemia remains an important goal in diabetes management.