LEADER Trial results from the ADA
The results of the Liraglutide Effect and Action in Diabetes – Evaluation of Cardiovascular Outcome Results (LEADER) trial were presented during a special symposium at the American Diabetes Association meeting in New Orleans on 13th June 2016. LEADER is a cardiovascular safety trial, mandated for all new diabetes medications by the FDA, which began in 2010. 9,340 patients, recruited in 32 countries, were allocated either to liraglutide or placebo and followed for a minimum of 3.5 years. Most patients – 81.3% – had a prior cardiovascular (CV) event, whilst the remainder were at high CV risk.
The trial showed that liraglutide significantly reduced the primary end-point of major cardiovascular events (MACE) by 13%, compared with placebo. This was driven by a significant 22% reduction in cardiovascular death although the other MACE components (non-fatal MI and non-fatal stroke) were also trending downwards. All-cause mortality was also significantly lowered by 15% whilst there was no evidence of any increase in heart failure, which has been reported with other incretin anti-diabetes medications.
Liraglutide was associated with a small but significant reduction in HbA1c (0.4%) in-keeping with the trial design, which aimed for equivalent glycaemic control between the study arms. Despite this, the risk of severe and total hypoglycaemia was reduced in the liraglutide-treated patients. Subjects on active medication also lost an average of 2.3Kg weight, had a small reduction in systolic blood pressure (1.2mmHg) and a mean increase in pulse rate of 3 bpm.
Trial follow-up was incredibly high with over 99.5% in both treatment arms and liraglutide was well tolerated. There was no signal for an increase in pancreatitis and malignancies were balanced between the liraglutide and placebo groups. No other unexpected safety signals emerged in the study.
Professor Steve Bain