Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial

The effect of sodium glucose cotransporter 2 inhibition with empagliflozin on microalbuminuria and macroalbuminuria in patients with type 2 diabetes

“…Previous clinical studies in type 2 diabetes patients with and without CKD have shown that SGLT2 inhibition is associated with an acute but modest decline in eGFR within 3-6 weeks of treatment initiation, followed by a period of stable renal function for 52-104 weeks; this change is reversible after drug cessation for 2 weeks [17,23,24]. Notably, within this same treatment period, renal safety assessments of SGLT2 inhibitors have also reported a reduction in UACR or urinary albumin excretion in patients with type 2 diabetes and CKD [15,24]. Moreover, in a dedicated study of patients with stage 3 CKD, the SGLT2 inhibitor dapagliflozin failed to show a significant effect on HbA 1c at 24 weeks, yet still reduced albuminuria, BP and weight [23].…”

“…Finally, though we observed a substantial effect of empagliflozin on albuminuria reduction over 24 weeks, the effect on longer-term reduction and on glomerular function rate requires further study. However, the effect of SGLT2 inhibition on UACR with empagliflozin, dapagliflozin and canagliflozin is present by approximately 4 weeks and tends not to dissipate over time [15,23,24], highlighting that the uniform use of UACR endpoints at 24 weeks is acceptable for this analysis.…”

“…Study design and entry criteria for all five trials have been published [7][8][9][10]15] (see electronic supplementary material [ESM] Methods). In four studies, patients with eGFR ≥ 30 ml min −1 1.73 m −2 were randomised to receive empagliflozin 10 mg, empagliflozin 25 mg or placebo once daily for 24 weeks as monotherapy or add-on therapy to background glucose-lowering medication.…”

“…In four studies, patients with eGFR ≥ 30 ml min −1 1.73 m −2 were randomised to receive empagliflozin 10 mg, empagliflozin 25 mg or placebo once daily for 24 weeks as monotherapy or add-on therapy to background glucose-lowering medication. In the fifth study (EMPA-REG RENAL), which included individuals with type 2 diabetes and chronic kidney disease (CKD), patients with CKD stage 2 received empagliflozin 10 mg, empagliflozin 25 mg or placebo, and patients with CKD stage 3 or stage 4 received empagliflozin 25 mg or placebo once daily for 52 weeks as add-on therapy [15]. UACR at 24 weeks was used in this analysis to remove the potential confounder of treatment length across trials.…”

SGLT2-Inhibitoren – Effektive Blutzuckerregulation über die Niere

“…Eine signifikante Glukosurie mit SGLT2-Hemmern kann nur dann erzielt werden, wenn noch eine gute Nierenfunktion be steht. Mit abnehmender Nierenfunk tion verringert sich die Menge der frei filtrier ten Glukosemenge im Primärharn und entsprechend sinkt der blutzuckersen kende Effekt dieser Medikamente [14]. Daher sollte bei Patienten mit einer eGFR < 60 ml/min/1,73m 2 keine Therapie mit Empagliflozin begonnen und bei einer persistierenden eGFR < 45 ml/min/1,73m 2 aufgrund mangelnder Wirksamkeit abge setzt werden [4].…”