Physicians' Academy for Cardiovascular Education

GLP-1 receptor agonist therapy associated with decreased CV risk in T2DM patients with CKD

Effects of Liraglutide versus Placebo on Cardiovascular Events in Patients with Type 2 Diabetes and Chronic Kidney Disease: Results from the LEADER Trial

Literature - Mann JFE, Fonseca V, Mosenzon O et al. - Circulation 2018; published online ahead of print

Introduction and methods

Patients with type 2 diabetes (T2DM) and chronic kidney disease (CKD) have an increased cardiovascular (CV) risk. Furthermore, low estimated glomerular filtration rate (eGFR) and albuminuria are independent predictors of CV outcomes [1,2]. However, it is unclear whether therapeutic interventions to decrease CV risk improve outcomes in these patients. In the Liraglutide Effect and Action in Diabetes: Evaluation of CV outcome Results (LEADER) trial [3,4], liraglutide therapy was associated with a reduced risk of CV outcomes, all-cause death and renal outcomes compared with placebo, in T2DM patients with established CV disease on standard of care.

LEADER was a multicenter, double-blind, placebo-controlled trial, which randomized T2DM patients at high CV risk to receive 1:1 liraglutide (1.8 mg daily or maximum tolerated dose) or placebo, on top of standard of care. The study was designed to recruit a subgroup of at least 660 patients with an eGFR<60 mL/min/1.73 m2, approximately 220 patients with severe renal impairment (eGFR <30 mL/min/1.73 m2), and at least 440 patients with moderate renal impairment (CKD stage 3; eGFR 30–60 mL/min/1.73 m2).

This posthoc analysis assessed the effect of liraglutide versus placebo on CV and safety outcomes in subgroups of patients with eGFR <60 mL/min/1.73 m2 versus eGFR ≥60 mL/min/1.73 m2, and those with micro/macroalbuminuria (<30 mg/g versus ≥30 mg/g creatinine), versus those without albuminuria at randomization. The primary outcome was a composite of CV death, non-fatal myocardial infarction (MI), or non-fatal stroke.

Main results


In patients with T2DM and CKD at high CV risk, liraglutide treatment was associated with fewer CV outcomes, similarly to patients without CKD.


Show references

Find this article online at Circulation

Share this page with your colleagues and friends: