This article is more than 5 years old. Information may no longer be current.
LEADER: Baseline CVD medication use does not explain liraglutide CV benefit
Click Here to Manage Email Alerts
SAN DIEGO — Further analyses of results from the LEADER trial revealed that baseline HbA1c, cardiovascular medication use and antihypgerglycemic medication use at study entry could not explain the cardiovascular benefit of liraglutide over placebo in adults with type 2 diabetes.
The primary outcome of the original Liraglutide Effect and Action in Diabetes — Evaluation of Cardiovascular Outcome Results (LEADER) trial aimed to determine the effect of the glucagon-like peptide 1 receptor agonist liraglutide (Victoza, Novo Nordisk) compared with placebo on CV outcomes including CV death, nonfatal myocardial infarction and nonfatal stroke. Results showed that liraglutide reduced the risk for 3-point major adverse cardiac events by 13%, risk for all-cause death by 15% and risk for CV death by 22% vs. placebo, while lowering HbA1c and body weight.
“It’s almost a year ago, to the date, when we presented the results of the LEADER study at the [American Diabetes Association 2016 Scientific Sessions],” Richard E. Pratley, MD, senior investigator at the Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, said during a presentation. “It was a culmination of a huge effort. There were a lot of people involved in making LEADER a success. I don’t think you can underestimate the amount of work that goes into a trial like this to get to this endpoint.”
In the additional analyses, presented here, the researchers examined the occurrence of all CV events — instead of just first events — and the amount was still lower in the liraglutide group vs. the placebo group (725 events vs. 870 events; HR = 0.86; 95% CI, 0.78-0.95).
When participants were entered into the LEADER trial, all were very well treated at baseline: more than 90% were on statins and hypertensive therapy, three-quarters were on lipid-lowering drugs, two-thirds were on platelet aggregation inhibitors.
“The question rises, does any of this make a difference for the outcomes? So, we analyzed that with a series of studies,” Pratley said. “The data show there were not significant effects on the overall HR, so the benefits of liraglutide treatment aren’t affected by background CV medication.”
Further, a larger number of participants were on antihyperglycemic medications at baseline; 75% were on metformin, half were on sulfonylureas and 45% or so were on insulin.
“Now the question is, would any of these have an impact on CV results? So, we examined whether not the primary outcomes were affected by insulin use at baseline and the answer is that for people who were on and who were not on insulin [the risk] was very similar,” Pratley said. “Presence of insulin at baseline did not affect the benefit seen with liraglutide.”
According to Pratley, some benefits of GLP-1 receptor agonists have been shown in clinical models, but “the bottom line is, in humans, we don’t actually know what the mechanism is for liraglutide’s benefit.”
Steven E. Nissen, MD, MACC, chairman of the Robert and Suzanne Tomsich Department of Cardiovascular Medicine at Cleveland Clinic’s Sydell and Arnold Miller Family Heart and Vascular Institute, added that results from trials like LEADER, combining diabetes populations and risks for CV events, give some perspective on benefits and risks of diabetes medications and CV events.
“We take care of the same patients,” he said. “Now more than 50% of the patients with coronary diseases are diabetic. So, coming together, these two communities — cardiovascular medicine and diabetes — to determine how best to treat these patients is an incredibly important societal priority. I am just so delighted that over the last decade we have really emerged with, what I think is now a triumph of evidence-based medicine. For the first time, we really have the evidence we need to understand these drugs and how they can impact the most important cause of morbidity and mortality in patients that we both are treating.” – by Amber Cox
Reference:
Pratley RE, et al. New Learnings from the Results of the Liraglutide Effect and Action in Diabetes — Evaluation of Cardiovascular Outcome Results (LEADER) trial. Presented at: American Diabetes Association 77th Scientific Sessions; June 9-13, 2017; San Diego.
Disclosures: Nissen reports various financial ties with AbbVie, Amgen, AstraZeneca, Cerenis Therapeutics, Eli Lilly and Company, Esperion Therapeutics, Medtronic, Orexigen Therapeutics, Pfizer and The Medicines Company. Pratley reports various financial ties with AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, GlaxoSmithKline, Hanmi Pharmo Co. Ltd., Janssen Pharmaceuticals, Lexicon Pharmaceuticals, Ligand Pharmaceuticals, Merck, Novo Nordisk, Sanofi Aventis, Takeda Development Center Americas Inc. and Takeda Pharmaceutical Company Limited.