Cardiovascular and kidney implications of the initial response in estimated glomerular filtration rate to sodium glucose cotransporter-2 inhibition with empagliflozin: the ‘eGFR dip’ in EMPA-REG OUTCOME

Background Empagliflozin (EMPA) reduces cardiovascular and kidney risk in patients with type 2 diabetes (T2D) and cardiovascular disease (CVD). EMPA induces an initial ‘dip’ in mean estimated glomerular filtration rate (eGFR).

Methods 6,668 Participants of EMPA-REG OUTCOME treated with EMPA 10mg, 25mg or placebo (PBO) and eGFR available were categorised by initial percentage eGFR change from baseline at week 4. Impact of an ‘eGFR dip’ >10% on risk reduction with EMPA for CV and kidney outcomes was assessed in a Cox regression landmark analysis adjusting for such ‘eGFR dip’.

Results ‘eGFR dip’ of >10% from baseline at Week 4 occurred in 28.3% participants on EMPA versus 13.4% on PBO; an eGFR decline of >30% in 1.4% and 0.9%, respectively. Odds ratio [OR; 95% CI] for an ‘eGFR dip’ with EMPA vs. PBO was 2.7 [2.3–3.0]. Diuretic use and/or higher KDIGO risk category at baseline were predictive of an ‘eGFR dip’ in EMPA vs. PBO. ‘eGFR dip’ did not affect risk reduction for CV death, hospitalization for heart failure (HHF) or the primary kidney outcome. Adverse events, especially acute renal failure rates, were lower or similar in EMPA vs. PBO, regardless of baseline predictive factors for an ‘eGFR dip’.

Conclusion T2D patients with more advanced kidney disease and/or on diuretic therapy at baseline were more likely to have an initial ‘eGFR dip’ >10% with EMPA. EMPA treatment was safe and associated with improved CV death, HHF and kidney outcomes, regardless of baseline predictive factors or such initial ‘eGFR dip’.

Publication History

Article published online:
06 May 2021