Will LEADER change the way we treat diabetes?

By Lisa Foster-McNulty, MSN, RN, CDE

At the American Diabetes Association (ADA) 2016 Scientific Sessions meeting held in June in New Orleans, there was huge interest in the results of the Liraglutide Effect and Action in Diabetes:  Evaluation of Cardiovascular Outcome Results (LEADER) trial of the glucose-lowering drug liraglutide.  You may be more familiar with this drug, made by Novo Nordisk, under its trade name of Victoza.  The FDA mandated cardiovascular safety study for a diabetes drug to show cardiovascular benefit, as opposed to mere lack of harm.  This was the first study on a glucagon-like peptide 1 (GLP1) receptor agonist medication.  The cardiovascular effect of liraglutide when added to standard care in patients with type 2 diabetes was not known.

This was a double blind study of patients with type 2 diabetes and high cardiovascular risk, and participants were assigned to receive liraglutide or placebo.  The primary endpoint/outcome of the study was the first occurrence of what the researchers called the three-point major adverse cardiac event (MACE) components, which were cardiovascular death, nonfatal heart attack, and nonfatal stroke.  The researchers expected that liraglutide would be noninferior to placebo with regard to the primary outcome, meaning that they thought that participants in the liraglutide group wouldn’t have any more cardiovascular problems than the participants in the placebo group.

There were 9340 participants randomized to either the treatment group or the placebo group, and they were followed for about 3.8 years on average.  The primary outcome happened in significantly fewer patients in the liraglutide group (608 of 4668 patients, or 13%) versus the placebo group (694 of 4672, or 14.9%).  In the group treated with Liraglutide, fewer (219, or 4.7%) patients died from cardiovascular causes than in the placebo group (278, or 6%), representing a 22% lower rate of cardiovascular death in the liraglutide group.  The death rate from any cause was lower in the liraglutide group (381 patients, 8.2%) compared to the placebo group (447 patients, 9.6%).  Although it was not statistically significant, the rates of nonfatal heart attack, nonfatal stroke, and hospitalization for heart failure were lower in the liraglutide group than the placebo group.  Additionally, the incidence of pancreatitis was lower in the liraglutide group than in the placebo group, although this did not reach statistical significance.

While this study focused on Type 2 diabetes, it’s important to remember that ALL people with diabetes have elevated risk for cardiovascular disease.  Moreover, some people with Type 1 diabetes use a GLP-1 drug such as Victoza off label.  Might there also be a benefit to that population in using Victoza?  We don’t know but it raises an interesting question.

It’s exciting to see that there was actually a statistically significant reduction in the rates of major adverse cardiovascular events in type 2 diabetes patients at elevated cardiovascular risk.  It would be so beneficial  to have medications that not only manage high blood glucose levels with diabetes but also have the potential to modify risk for cardiovascular disease and death!