Evidence regarding the effects of G

Evidence regarding the effects of GLP‐1RAs on CV outcomes has been mostly favourable72: two of the four CV outcome studies showed a significant reduction in a three‐point MACE (liraglutide in LEADER and semaglutide in SUSTAIN‐6), and two reported no significant change (exenatide in EXSCEL and lixisenatide in ELIXA; Table 2).73-76 The LEADER trial randomized 9340 patients with type 2 diabetes who were at high CV risk to placebo or liraglutide 0.6 to 1.8 mg/d for 3.1 years. The three‐point MACE was reduced by 13% in the liraglutide group, with a 22% reduction in CV death and a 15% reduction in total mortality. There was also a non‐significant numerical reduction in non‐fatal MI and non‐fatal stroke.74 The Kaplan–Meier curves for the three‐point MACE showed a separation of events between liraglutide‐ and placebo‐treated patients after 12 to 18 months, suggesting that the beneficial effect of liraglutide is not immediate and may be mediated by a reduction in atherosclerosis‐related events.