In patients with type 2 diabetes and high cardiovascular (CV) risk, long-term use of liraglutide may decrease risk of death from CV events, as well as risk of nonfatal stroke and nonfatal myocardial infarction, a recent study found.
The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial randomized 9,340 patients ages 50 years and older to 1.8 mg of liraglutide per day via injection or placebo in addition to standard care. Results of the double-blind, multinational trial, which was funded by Novo Nordisk and the National Institutes of Health, were published online on June 13 by the New England Journal of Medicine.
Each cohort had a follow-up period of a median of 3.8 years. About 81% of all patients had established CV disease, chronic kidney disease of stage 3 or higher, or both. At baseline, the mean duration of diabetes was 12.8 years, and the mean glycated hemoglobin level was 8.7%.
The primary composite outcome was first occurrence of death from CV causes, nonfatal (including silent) myocardial infarction, or nonfatal stroke. This outcome occurred in fewer patients in the liraglutide group (608 of 4,668 patients [13.0%]) than in the placebo group (694 of 4,672 patients [14.9%]) (hazard ratio [HR], 0.87; 95% CI, 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority).
In addition, death from CV causes occurred in fewer patients in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 patients [6.0%]) (HR, 0.78; 95% CI, 0.66 to 0.93; P=0.007). The rate of death from any cause was also lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (HR, 0.85; 95% CI, 0.74 to 0.97; P=0.02).
Although the occurrence of nonfatal myocardial infarction and nonfatal stroke was also lower in the liraglutide group than in the placebo group, the differences were not statistically significant. Patients in the liraglutide group were more likely than those receiving placebo to experience adverse events (mostly gastrointestinal) and discontinue the treatment regimen (difference, 2.2 percentage points).
The study authors noted limitations to their work, such as how patients were only followed for 3.5 to 5.0 years and how the trial recruited patients at high risk for CV events who had a baseline glycated hemoglobin level of 7% or more, which may reduce the applicability of these findings to patients at lower risk.
Most other trials of newer medications for type 2 diabetes have not shown similar results, and differences among the participants do not fully explain this divergence, noted an accompanying editorial. “We are left with differences that appear encouraging, yet are not a ‘home run’ with regard to the management of diabetes,” the editorialist wrote, stressing the need for “controlled and comparative effectiveness trials that uniformly combine newer agents with older agents.”