LEADER: Hypoglycaemia, but not CVD history, may eclipse liraglutide’s CV benefits
The protective effects of liraglutide against the risks of cardiovascular (CV) events and deaths may be reduced in patients with type 2 diabetes (T2D) who experienced severe hypoglycaemia, but were independent of patient’s history of CV events at baseline, according to post hoc analyses of the LEADER* trial.
Previously, primary analysis of the LEADER trial has demonstrated that liraglutide led to reduced risks of major adverse cardiac events (MACE; a composite of myocardial infarction [MI], stroke, or CV-related death) and all-cause mortality. The risk of severe hypoglycaemia was also lower with liraglutide than placebo (rate ratio [RR], 0.69). [N Engl J Med 2016;375:311-322]
In the current studies presented at IDF 2017, the investigators explored if certain conditions, such as severe hypoglycaemia or prior CV events, were associated with CV outcomes in two separate post hoc analyses.
Compared with participants without severe hypoglycaemia, those who experienced severe hypoglycaemia were significantly more likely to experience MACE (RR, 5.4; p<0.01), CV death (RR, 9.5; p<0.01), and death from any cause (RR, 8.6; p<0.001) within 15 days of a hypoglycaemic episode. [IDF 2017, abstract OP-0007]
The increases in risks for MACE, CV death, and all-cause mortality were also observed within 30 days of a hypoglycaemic episode, and up to 60 days of follow-up compared with those without severe hypoglycaemia (RR, 3.1; p<0.01 for MACE, 6.7; p<0.0001 for CV death, and 8.9; p<0.0001 for all-cause death).
“Patients experiencing severe hypoglycaemia were at greater risk of CV events and death, particularly early after the hypoglycaemic episode. Reducing severe hypoglycaemia remains a cornerstone of diabetes management,” according to the researchers.
The CV benefits conferred by liraglutide were unchanged after excluding patients with severe hypoglycaemia (constituting 5 percent of all MACE) from the analysis.
Another post hoc analysis was performed to assess the association between existing CV disease at baseline and risk of CV events. [IDF 2017, abstract OP-0009]
Among the patient subgroup with prior MI and/or stroke at baseline (n=3,692), the composite primary endpoint of MI, stroke, and CV death was reduced by 16 percent with liraglutide vs placebo (hazard ratio [HR], 0.84, 95 percent confidence interval [CI], 0.72–0.97).
The risk of composite primary outcome was also reduced in patients without prior MI and/or stroke who received liraglutide vs placebo (HR, 0.89, 95 percent CI, 0.76–1.05).
In addition, the protective effects of liraglutide against CV death were observed in both subgroups of patients, with risk reductions regardless of the presence of prior CV events.
“These data suggest that liraglutide reduces CV events in both primary and secondary prevention,” said study co-author Dr Michael Nauck of St. Josef-Hospital Clinic-University Hospitals the Ruhr-University of Bochum in Bochum, Germany.