Treatment with liraglutide for type 2 diabetes (T2D) was not associated with an increased risk for hospitalization for heart failure (HF) or cardiovascular (CV) death in patients with vs without a history of HF, according to a study published in the Journal of the American College of Cardiology.
In the multinational, double-blind, randomized Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results trial (LEADER; ClinicalTrials.gov identifier: NCT01179048), 9380 patients with T2D (ages ≥50 years for patients with established CV disease or chronic kidney disease; ages ≥60 years for patients with ≥1 CV risk factor) were enrolled. Participants were randomly assigned to receive liraglutide (1.8 mg once-daily) and standard care (n=835 with HF; n=3833 without HF) or placebo and standard care (n=832 with HF; n=3840 without HF) and were followed for 3.5 to 5 years. The study’s primary endpoint was time from randomization to first occurrence of a composite of major adverse CV events (MACE; ie, CV death, nonfatal myocardial infarction, or nonfatal stroke).
There were fewer deaths in participants receiving liraglutide vs placebo, whether they had a history of HF (hazard ratio [HR], 0.89; 95% CI, 0.70-1.14) or no history of HF (HR, 0.83; 95% CI, 0.70-0.97; P =.63 for interaction).
Liraglutide had comparable effects on MACE in participants with vs without a history of HF (HR, 0.81; 95% CI, 0.65-1.02; and HR, 0.88, 95% CI, 0.78-1.00, respectively). In the liraglutide group, there were 275 first nonfatal myocardial infarction events and 152 first nonfatal stroke events, compared with 304 and 163 events, respectively, in the placebo group (P =.29 and P =.99, respectively). There was no increased risk for hospitalization for HF in either group.
Study limitations include a lack of information on the etiology of HF and insufficient statistical power to detect treatment interactions between subgroups. “When considering the effect of other glucose-lowering therapies on HF, the sodium-glucose cotransporter-2 inhibitors empagliflozin, canagliflozin, and dapagliflozin have been associated with early and significant decreases in the risk of HF outcomes vs placebo in people with T2D,” noted the study authors. “Further studies should investigate the effect of [glucagon-like peptide-1] analogs in patients with T2D and HF with reduced or preserved ejection fractions who are well characterized with respect to etiology and biomarkers, and clarify the mechanisms underlying the impact on clinical outcomes.”
Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.
Marso SP, Baeres FMM, Bain SC, et al. Effects of liraglutide on cardiovascular outcomes in patients with diabetes with or without heart failure. J Am Coll Cardiol. 2020;75(10):1128-1141.