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

Conclusion

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

References

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Find this article online at Circulation

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