Cardiovascular Outcomes with Liraglutide: An Update following LEADER

Diabetes Mellitus is one of the most important causes of cardiovascular disease in the United States and worldwide. Few antidiabetic drugs (e.g. Rosiglitazone) have faced cardiovascular (CV) safety related controversies in the recent past. The FDA mandatory advisory states that the CV safety concerns of any new antidiabetic drug should be thoroughly addressed in a dedicated longitudinal outcome trial. Liraglutide, a long-acting GLP-1 agonist, approved as a 2nd line agent in the treatment of type 2 diabetes mellitus (DM), has shown some promising effects on the cardiovascular system in various preclinical and early clinical studies. In accordance with the FDA recommendation, a large, multicenter trial (LEADER) was undertaken in 2010 to look for long-term CV outcome data on liraglutide. Primary outcome (Death due to CV causes, nonfatal MI or, nonfatal stroke) occurred in significantly fewer patients in the liraglutide group, with a lower incidence of cardiovascular and all-cause mortality. Besides, a better glycemic control, fewer hypoglycemic events, significant weight loss, and beneficial effects on nephropathy were observed in patients on Liraglutide. ELIXA trial on Lixisenatide did not reveal any significant CV benefit. So, Results from the ongoing CV outcome trials on other GLP-1 agonists (EXSCEL for Exenatide, HARMONY for Albiglutide, and REWIND study for Dulaglutide) will guide us better to determine whether the observed benefit is indeed a class effect or a molecule effect. Here we have summarized all the cardiovascular outcome data so far available on liraglutide, with special reference to the recently published LEADER trial results.