Abstract 16904: Cardiovascular Safety of Liraglutide: A Pooled Analysis from Phase II and III Liraglutide Clinical Development Studies
Introduction: Liraglutide is a human glucagon-like peptide-1 (GLP-1) analog approved for patients with type 2 diabetes. The US FDA currently recommends analysis of major adverse cardiovascular events (MACE) for new anti-diabetes drugs. Since liraglutide's NDA was submitted prior to this regulatory requirement, the objective of this work was to perform a retrospective MACE analysis of the liraglutide development studies.
Methods: Pooled analysis of patients in all completed intermediate/long-term randomized trials plus open label extensions of liraglutide drug development studies. Individuals with and without type 2 diabetes age 18-80, hemoglobin A1c 7-11% and BMI <45 kg/m2 exposed to liraglutide 0.045-3.0 mg/day, active control or placebo were included. MACE (death, MI or stroke) were retrospectively identified using medical dictionary for regulatory activities (MedDRA) terms with 3 search categories of varied sensitivity (broad, narrow and custom) that were based on the number of search terms associated with MI and stroke. MedDRA terms also identified as serious MACE by site investigators were adjudicated post hoc by an independent clinical event committee blinded to treatment.
Results: In 15 phase 2 and 3 trials including 6,638 patients (4,257 exposed to liraglutide), there were a total of 44, 43, and 32 serious MACE using broad, narrow and custom search criteria, respectively. After expert evaluation, 39, 39 and 31 serious MACE identified using broad, narrow and custom criteria, respectively, were adjudicated as MACE. The point estimate of the incidence ratio for MACE associated with liraglutide was <1.0 for each MedDRA search (Figure).
Conclusions: In each MACE analysis, the point estimates for liraglutide was <1.0 and upper 95% CI was <1.8, a specified upper bound in FDA guidance for new anti-diabetes drugs. Liraglatide will be prospectively evaluated in LEADERTM, a large scale, international, randomized controlled cardiovascular outcomes trial.
- © 2010 by American Heart Association, Inc.