Findings from a post-hoc analysis of the LEADER cardiovascular (CV) outcomes trial showed that treatment with liraglutide resulted in similar reductions in the risk of major CV events in people with type 2 diabetes (T2DM) at high CV risk, regardless of whether or not they experienced an episode of severe hypoglycemia during the trial. Results were presented yesterday at the American Diabetes Association 77th Scientific Sessions.

For the overall LEADER population, regardless of treatment group, people who experienced a severe hypoglycemic episode were at a significantly greater risk of major CV adverse events (CV death, non-fatal myocardial infarction (MI) or non-fatal stroke), CV-death or non-CV death. The risk of a CV event was far greater within 60 days of a severe hypoglycemic episode occurring. At the same time, people treated with liraglutide experienced significantly fewer episodes of severe hypoglycemia when compared to placebo, both in addition to standard of care.

"It appears that patients who experience severe hypoglycemia are at an increased risk of cardiovascular events," said Steven P. Marso, medical director for Cardiovascular Services at HCA Midwest Health Heart and Vascular Institute, Kansas City, TX, US and co-chair of the LEADER Steering Committee. "While the lower incidence of severe hypoglycemia with liraglutide could contribute to the observed beneficial effect on major cardiovascular events in LEADER, this new analysis indicates that the results cannot be explained by these differences in hypoglycemia."

Liraglutide is a human glucagon-like peptide-1 (GLP-1) analogue with an amino acid sequence 97% similar to endogenous human GLP-1. LEADER was a multicenter, international, randomized, double-blind, placebo-controlled trial investigating the long-term (3.5-5 years) effects of liraglutide (up to 1.8 mg) compared to placebo, both in addition to standard of care, in people with T2DM at high risk of major CV events. Standard of care consisted of lifestyle modifications, glucose-lowering treatments and CV medications. LEADER was initiated in September 2010 and randomized 9,340 people with T2DM from 32 countries. The primary endpoint was the first occurrence of a composite CV outcome comprising CV death, non-fatal MI or non-fatal stroke.

Over a median follow-up of 3.8 years, liraglutide significantly reduced the risk of the composite primary endpoint by 13% vs placebo. There was a significant 22% reduction in CV death with liraglutide treatment vs placebo and non-significant reductions in non-fatal MI and non-fatal stroke.

In Europe, liraglutide is indicated for the treatment of adults with T2DM to achieve glycemic 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 glycemic control. In the US, liraglutide was approved in 2010 as an adjunct to diet and exercise to improve blood glucose control in adults with T2DM.

Source: Press release Novo Nordisk, June 13 2017