Abstract 12630: Cardiovascular Safety of Liraglutide: Pooled Analysis of Major Adverse Cardiovascular Events across Weight Management and Type 2 Diabetes Development Programs

The cardiovascular safety of liraglutide in individuals with overweight/obesity and those with type 2 diabetes (T2D) is unknown. A meta-analysis of five phase II/III liraglutide (dose up to 3.0 mg) weight management (WM) trials was performed. Additional sensitivity meta-analyses of 21 liraglutide T2D trials (dose up to 1.8 mg) and a pre-specified pooled analysis of all WM and T2D trials (27 trials; WM+T2D) were also conducted. The primary endpoint was first occurrence of adjudicated major adverse cardiovascular events (MACE) (non-fatal myocardial infarction, non-fatal stroke or cardiovascular death) with liraglutide (any dose) or pooled total comparator (placebo, active) and analysis was using a Cox proportional hazards model stratified by trial. Prospective adjudication (blinded, independent) was implemented in three of the WM trials; post-hoc adjudication was conducted for all other trials. For WM trials, the observation period was from the first drug dose to the last drug dose plus a 30-day follow-up; for the SCALE Obesity and Prediabetes trial, data to October 1, 2014 were included. For WM trials (liraglutide: n=3,872; comparator: n=2,036), baseline characteristics were: 71% women; history of CV disease, 9%; mean age, 47 yrs; mean BMI, 38 kg/m 2 . For T2D trials (liraglutide: n=5,511; comparator: n=2,748): 43% women; history of CV disease, 13%; mean age, 56 yrs; mean BMI, 30 kg/m 2 . In WM trials (n=20 events), the hazard ratio (HR) [95% confidence interval (CI)] for MACE (liraglutide/comparator) was 0.45 [0.18; 1.10] (Figure 1A). In T2D trials (n=49 events), the HR was 0.64 [0.35, 1.15] (Figure 1A). For the WM+T2D analysis (n=69 events), the HR was 0.57 [0.35, 0.94] (Figure 1B). In a pooled analysis of WM+T2D trials, MACE was significantly lower in patients treated with liraglutide. The dedicated cardiovascular outcomes trial, LEADER, will provide further insights into the cardiovascular safety of liraglutide.