The Effect of Empagliflozin on Kidney Injury Markers in Subjects with Type 2 Diabetes and Cardiovascular Disease: A Sub-analysis of the EMPA-HEART CardioLink-6 Trial
Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors confer profound cardiorenal protection in type 2 diabetes (T2D). To better define potential mechanisms that underlie the renal benefits of SGLT2 inhibition, we assessed changes in various urinary biomarkers, sodium and glucose excretion, in a prespecified sub-analysis of the EMPA-HEART CardioLink-6 trial. In a cohort of patients with T2D at relatively low risk for diabetic kidney disease progression, empagliflozin treatment for six months reduced urinary kidney injury molecule-1 (KIM-1) excretion by 34% (p=0.03). No significant differences were observed with the other renal biomarkers. The reduction in KIM-1, in the absence of changes in albuminuria, raises the possibility that SGLT2 inhibitors act primarily to protect the proximal tubule, thus delaying the progression of diabetic kidney disease. Importantly, empagliflozin treatment did not significantly increase sodium excretion, suggesting that SGLT2 inhibitor-induced plasma volume reduction is a consequence of osmotic (glucose) diuresis rather than natriuresis.
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Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence.
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