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/m2. 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/m2.
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.
Author Disclosures: I.D. Caterson: Research Grant; Modest; Novo Nordisk, Pfizer, Bristol-Myers Squibb, SFI. Speakers Bureau; Modest; Servier Laboratories, Novo Nordisk, Ache, Pfizer. Consultant/Advisory Board; Modest; Exscel Trial Operations Committee, SCOUT Trial, Sansom Institute for Health Research, University of SA, Children’s Medical Research Institute. Other; Modest; Chair of Executive Management Committee of the bariatric surgical register, Obesity Surgery Society of Australia and New Zealand. S.C. Bain: Consultant/Advisory Board; Modest; AstraZeneca, Boerhinger Ingelheim, Bristol Myers-Squibb, Janssen, Eli Lilly & Co, Merck Sharp & Dohme, Novo Nordisk, Omnia-Med, Sanofi, Glycosmedia. J. Gross: Research Grant; Modest; Boehringer Ingelheim, Eli Lilly & Co, GlaxoSmithKline, Mannkind Corporation, Novo Nordisk. Consultant/Advisory Board; Modest; Boehringer Ingelheim, Eli Lilly & Co, Novo Nordisk. J. House: Consultant/Advisory Board; Modest; Washington University, Saint Louis, MO. A.C. Salisbury: Other; Modest; Novo Nordisk. F.M. Baeres: Employment; Significant; Novo Nordisk. Ownership Interest; Significant; Novo Nordisk. M. Donsmark: Employment; Significant; Novo Nordisk. Ownership Interest; Significant; Novo Nordisk. S.P. Marso: Research Grant; Significant; Novo Nordisk, The Medicines Company, AstraZeneca, Bristol-Myers Squibb. Consultant/Advisory Board; Significant; Novo Nordisk, St Jude Medical.
- © 2015 by American Heart Association, Inc.