Liraglutide and CV Outcomes in Diabetes and Chronic Kidney Disease

Study Questions:

What are the effects of liraglutide on cardiovascular (CV) and safety outcomes in subgroups of patients with type 2 diabetes (T2D) and chronic kidney disease (CKD)?

Methods:

The investigators performed a post hoc analysis of the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial data to analyze liraglutide’s treatment effects in patients with and without kidney disease. LEADER was a multicenter, double-blind, placebo-controlled trial that randomized patients with T2D and high risk of CV disease 1:1 to liraglutide or placebo, in addition to standard of care. The current analyses assessed outcomes stratified by baseline estimated glomerular filtration rate (eGFR; <60 vs. ≥60 ml/min/1.73 m2) and baseline albuminuria. The primary outcome (composite of CV death, nonfatal myocardial infarction [MI], or nonfatal stroke) and secondary outcomes, including all-cause mortality and individual components of the primary composite outcome, were analyzed using Cox regression.

Results:

Overall, 2,158 and 7,182 patients had baseline eGFR <60 or >60 ml/min/1.73 m2, respectively. In patients with eGFR <60 ml/min/1.73 m2, risk reduction for the primary composite CV outcome with liraglutide was greater (hazard ratio [HR], 0.69; 95% confidence interval [95% CI], 0.57-0.85) versus those with eGFR ≥60 ml/min/1.73 m2 (HR, 0.94; 95% CI, 0.83-1.07; interaction p = 0.01). There was no consistent effect modification with liraglutide across finer eGFR subgroups (interaction p = 0.13) and when analyzing eGFR as a continuous variable (interaction p = 0.61). Risk reductions in those with eGFR <60 versus ≥60 ml/min/1.73 m2 were: for nonfatal MI, HR, 0.74; 95% CI, 0.55-0.99 versus HR, 0.93; 95% CI, 0.77-1.13; for nonfatal stroke, HR, 0.51; 95% CI, 0.33-0.80 versus HR, 1.07; 95% CI, 0.84-1.37; for CV death, HR, 0.67; 95% CI, 0.50-0.90 versus HR, 0.84; 95% CI, 0.67-1.05; for all-cause mortality, HR, 0.74; 95% CI, 0.60-0.92 versus HR, 0.90; 95% CI, 0.75-1.07. Risk reduction for the primary composite CV outcome was not different for those with versus without baseline albuminuria (HR, 0.83; 95% CI, 0.71-0.97 and HR, 0.92; 95% CI, 0.79-1.07, respectively; interaction p = 0.36).

Conclusions:

The authors concluded that liraglutide added to standard of care reduced the risk for major CV events and all-cause mortality in patients with T2D and CKD.

Perspective:

This post hoc subgroup analysis of the LEADER trial reports that liraglutide reduced the risk of major adverse CV events and all-cause mortality compared with placebo in patients with CKD and in patients with albuminuria. These results suggest that liraglutide may be considered as an option for patients with T2D and CKD since these patients have a high CV risk burden. Given the post hoc, subgroup nature of the analysis, these results should be confirmed in a dedicated prospective study. Of note, among one third of the 7,020 EMPA-REG (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) subjects with an eGFR between 30 and 59 ml · min−1 · 1.73 m−2 with albuminuria, empagliflozin (a less expensive agent) also significantly reduced all CV events and all-cause mortality in these patients with CKD.

Clinical Topics: Diabetes and Cardiometabolic Disease, Prevention

Keywords: Albuminuria, Kidney Failure, Chronic, Diabetes Mellitus, Type 2, Glomerular Filtration Rate, Glucagon-Like Peptide 1, Metabolic Syndrome X, Myocardial Infarction, Primary Prevention, Renal Insufficiency, Chronic, Standard of Care, Stroke, Vascular Diseases


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