The study explores the temporal and subgroup disparities in the mediation effects of liraglutide and semaglutide on cardiovascular outcomes, specifically focusing on major adverse cardiovascular events (MACE). It examines how these effects vary over time and across different patient subgroups, including those with established cardiovascular diseases (CVDs) and those with an estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73 m2. The research utilizes data from the LEADER and SUSTAIN-6 trials, which involved a total of 9340 and 3297 subjects, respectively. The findings indicate that hemoglobin A1c (HbA1c) is the primary mediator of the effects of both liraglutide and semaglutide on MACE, with its influence increasing over time for liraglutide and remaining stable for semaglutide. However, the study also highlights that the mediation effects of HbA1c, urine albumin-to-creatinine ratio (UACR), and systolic blood pressure (SBP) on MACE vary across patient subgroups, particularly those with CVDs and those with eGFR < 60 ml/min/1.73 m2. These findings suggest that the underlying risk factors may play a significant role in the mediation effects of these medications.
