Diabetologie und Stoffwechsel 2016; 11 - P196
DOI: 10.1055/s-0036-1580943

Cardiovascular safety of liraglutide: Pooled analysis of Major adverse cardiovascular events across weight management and Type 2 Diabetes development programs

S Jacob 1, T Wehrhahn 2, I Caterson 3, S Bain 4, J Gross 5, J House 6, A Salisbury 6, 7, S Marso 8, F Baeres 9, M Donsmark 9
  • 1Praxis für Prävention und Therapie, Villingen-Schwenningen, Germany
  • 2Novo Nordisk Pharma GmbH, Mainz, Germany
  • 3Boden Institute, Charles Perkins Centre, University of Sydney, Sydney, Australia
  • 4Swansea University, Swansea, Wales, United Kingdom
  • 5Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
  • 6Saint Luke's Mid America Heart Institute, Kansas City, United States
  • 7University of Missouri-Kansas City School of Medicine, Kansas City, United States
  • 8University of Texas Southwestern Medical Center, Dallas, United States
  • 9Novo Nordisk A/S, Søborg, Denmark

A meta-analysis of five phase II/III liraglutide (up to 3.0 mg) weight management (WM) trials, additional sensitivity meta-analyses of 21 liraglutide type 2 diabetes (T2D) trials (up to 1.8 mg) and a pre-specified pooled analysis of WM+T2D trials (n = 27) were performed to assess liraglutide's cardiovascular safety in individuals with overweight/obesity and T2D.

The primary endpoint was first occurrence of adjudicated major adverse cardiovascular events (MACE) (non-fatal myocardial infarction, non-fatal stroke, cardiovascular death) with liraglutide (any dose) or pooled total comparator (placebo, active) using a Cox proportional-hazards model stratified by trial. Prospective adjudication (blinded, independent) was implemented in three WM trials; post-hoc adjudication was conducted for other trials. For WM trials, the observation period was from first to last drug dose plus 30-day follow-up; for SCALE Obesity and Prediabetes, data to 1October 2014 were included.

For WM trials (liraglutide: n = 3,872; comparator: n = 2,036), baseline characteristics were: 71% women; CV disease history, 9%; mean age, 47 years; mean BMI, 38 kg/m2. For T2D trials (liraglutide: n = 5,511; comparator: n = 2,748): 43% women; CV disease history, 13%; mean age, 56 years; 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]. In T2D trials (n = 49 events), HR was 0.64 [0.35, 1.15]. For the WM+T2D analysis (n = 69 events), HR was 0.57 [0.35, 0.94].

In this 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 liraglutide's cardiovascular safety.