Global healthcare company Novo Nordisk announced that Liraglutide 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% vs placebo (95% confidence interval [CI]: 0.78; 0.97, p=0.01), when added 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 vs placebo, both on top of standard of care, in a cardiovascular outcomes trial.
There was a significant 22% reduction in cardiovascular death with Liraglutide treatment vs 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).1, 2
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 vs placebo, both on top of 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.
Melvin D’souza, VP and GM of Novo Nordisk India, said: “I am excited about the positive outcomes of the LEADER trial related to cardiovascular safety. I am also confident that the LEADER trial outcome will make a significant difference in the lives of people with diabetes and the treating physicians in a big way in diabetes management.”
Prof Shashank R. Joshi, Endocrinologist, Lilavati & Bhatia Hospital, President Elect-Endocrine Society of India, said: “As per current edition of IDF Atlas, India is home to second largest number of people with diabetes in the world. As at least 68% people aged 65 or older with diabetes die from some form of heart disease, there is a strong correlation between cardiovascular disease and diabetes. Thus in management of type 2 diabetes, focus on reducing cardiovascular disease and its risk factors is a must. With this trial, I am positive that the treatment of diabetes will change for good”
Dr. V. Mohan, Chairman & Chief Diabetologist, Dr. Mohan's Diabetes Specialities Centre, President & Chief of Diabetes Research, Madras Diabetes Research Foundation, Chennai said “People with type 2 diabetes may have high blood pressure, abnormal cholesterol and high triglycerides and obesity, which can increase their risk of developing cardiovascular risk. With the LEADER trial results coming out positive, I can see diabetes treatment guidelines changing leading to improvement in diabetes care.”
Dr. Ambrish Mithal, Chairman and Head of Endocrinology and Diabetes division at Medanta, The Medicity, New Delhi, said: “Adults with diabetes are two to four times more likely to have heart disease or a stroke. With the announcement of these results, GLP-1 based therapies will have a major impact on present day diabetes management".
The proportion of adults experiencing adverse events was similar between the Liraglutide and the placebo groups (62.3% vs 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 1.8 mg) 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 comprised of lifestyle modifications, glucose-lowering treatments and cardiovascular medications.
LEADER 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.
Liraglutide is a human glucagon-like peptide-1 (GLP-1) analogue with an amino acid sequence 97% similar to endogenous human GLP-1. Liraglutide was launched in the EU in 2009 and is commercially available in more than 85 countries, treating more than 1 million people with type 2 diabetes globally.3, 4 In Europe, Liraglutide is indicated for the treatment of adults with type 2 diabetes to achieve glycaemic control as monotherapy, when metformin is considered inappropriate, and in combination with oral glucose-lowering medicinal products and/or basal insulin when these, together with diet and exercise, do not provide adequate glycaemic control.3 In the US, Liraglutide was approved in 2010 as an adjunct to diet and exercise to improve blood glucose control in adults with type 2 diabetes.
In India, Liraglutide was approved in 2010 and is indicated for the treatment of adults with T2D to achieve glycaemic control as monotherapy, when metformin is considered inappropriate, and in combination with oral glucose-lowering treatments and/or basal insulin when these, together with diet and exercise, do not provide adequate blood glucose control.