Empagliflozin reduced progression of kidney disease and cardiovascular death in patients with or without diabetes who are at high risk of disease progression

Abstract

Sodium glucose co-transporter inhibitor (SGLT2i) has emerged not only as a novel therapy to manage hyperglycaemia in people with type 2 diabetes but also shown to confer benefits in reducing a host of cardio-metabolic-renal outcomes. The SGLT2i, Empagliflozin has been shown to reduce cardiovascular death and improve outcomes from heart failure, but its effect in patients with chronic kidney disease (CKD) who are at risk for disease progression are not well understood. A study published in the New England Journal Medicine by the Empa-Kidney Collaborative group was designed to assess the effects of treatment with empaglifozin in a broad range of such patients. The study recruited patients with CKD who had an estimated glomerular filtration rate (eGFR) between 20 and 45 mL/minute/1.73 m2 of body-surface area, or who had an eGFR of between 45 and 90 mL/minute/1.73 m2 with a urinary albumin-to-creatinine ratio of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to <10 mL per minute per 1.73 m2, a sustained decrease in eGFR of ≥40% from baseline, or death from renal causes) or death from cardiovascular causes. 6609 patients underwent randomization. During a median of 2.0 years of follow-up, Empagliflozin was associated with a significant 28% reduction in the progression of kidney disease or death from cardiovascular causes. Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was also 14% lower in the empagliflozin group than in the placebo group, but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes or death from any cause. This finding support the wider use of empagliflozin for renal protection in patients irrespective of diabetes status. Reassuringly also, the rates of serious adverse events were similar between empagliflozin and placebo. To optimize clinical safety, clinical implementation of evidence derived from this study require collaborative working between renal and diabetes teams, emphasising the sick day rules for SGLT2i as well as close monitoring of renal and clinical outcomes.