The GLP-1 receptor analogue liraglutide (Victoza) significantly reduced the risk of the composite primary endpoint of cardiovascular (CV) death, non-fatal myocardial infarction (heart attack) or non-fatal stroke by 13% versus placebo, in addition to standard of care in 9,340 adults with type 2 diabetes at high CV risk.
The main results of the LEADER trial were presented at the American Diabetes Association's 76th Scientific Sessions (ADA 2016) and also published in the New England Journal of Medicine.
Liraglutide is the only approved GLP-1 receptor agonist to demonstrate a superior reduction of major CV events versus placebo, both in addition to standard of care, in a cardiovascular outcomes trial. There was a significant 22% reduction in cardiovascular death with liraglutide treatment versus placebo (95% CI: 0.66; 0.93, p=0.007) and reductions in non-fatal myocardial infarction (HR=0.88, 95% CI: 0.75; 1.03, p=0.11) and non-fatal stroke (HR=0.89, 95% CI: 0.72; 1.11, p=0.30).Professor Steve Bain, UK LEADER trial National Leader and Assistant Medical Director for Research & Development for ABM University Health Board and Clinical Lead for the Diabetes Research Unit, Wales, said: “Liraglutide is the first GLP-1 therapy that has been shown to significantly reduce the risk of major CV events and represents great progress in our understanding of liraglutide’s clinical profile. Given the important link between diabetes and CV complications, it is important to be able to trust that any diabetes treatment prescribed does not add to that risk. The study findings for liraglutide have surpassed our expectations in providing us with a tool that can effectively help to treat patients’ type 2 diabetes and control blood sugar levels, with the additional reassurance of reducing CV risk.”
All-cause death was significantly reduced by 15% with liraglutide compared to placebo (95% CI: 0.74; 0.97, p=0.02). The expanded CV endpoint was significantly reduced by 12% with liraglutide compared to placebo (95% CI: 0.81; 0.96, p=0.005). The expanded CV endpoint included the three components of the primary endpoint in addition to unstable angina leading to hospitalisation, coronary revascularisation and hospitalisation for heart failure.
From a mean baseline of 8.7% (both groups), there was a greater reduction in HbA1c with liraglutide versus placebo, in addition to standard of care, at three years (estimated treatment difference [ETD]: -0.40%, 95% CI: -0.45; -0.34). Weight loss was also sustained over three years with liraglutide treatment vs placebo (ETD: -2.3 kg, 95% CI: - 2.5; -2.0). Mean baseline weight was 91.9 kg and 91.6 kg, respectively.
The proportion of adults experiencing adverse events was similar between the liraglutide and the placebo groups (62.3% versus 60.8%, respectively). The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was non-significantly lower in the liraglutide group than in the placebo group.
LEADER was a multicentre, international, randomised, double-blind, placebo-controlled trial investigating the long-term effects of liraglutide up to 1.8mg compared to placebo, both in addition to standard of care, in people with type 2 diabetes at high risk of major cardiovascular events. Standard of care was defined as lifestyle modifications, selective glucose lowering treatments and cardiovascular medications. It was initiated in September 2010 and randomised 9,340 people with type 2 diabetes from 32 countries that were followed for 3.5–5 years. The primary endpoint was the first occurrence of a composite cardiovascular outcome comprising cardiovascular death, non-fatal myocardial infarction or non-fatal stroke.